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Sample records for arrestin content studied

  1. Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors.

    PubMed

    Gurevich, V V; Dion, S B; Onorato, J J; Ptasienski, J; Kim, C M; Sterne-Marr, R; Hosey, M M; Benovic, J L

    1995-01-13

    Arrestins play an important role in quenching signal transduction initiated by G protein-coupled receptors. To explore the specificity of arrestin-receptor interaction, we have characterized the ability of various wild-type arrestins to bind to rhodopsin, the beta 2-adrenergic receptor (beta 2AR), and the m2 muscarinic cholinergic receptor (m2 mAChR). Visual arrestin was found to be the most selective arrestin since it discriminated best between the three different receptors tested (highest binding to rhodopsin) as well as between the phosphorylation and activation state of the receptor (> 10-fold higher binding to the phosphorylated light-activated form of rhodopsin compared to any other form of rhodopsin). While beta-arrestin and arrestin 3 were also found to preferentially bind to the phosphorylated activated form of a given receptor, they only modestly discriminated among the three receptors tested. To explore the structural characteristics important in arrestin function, we constructed a series of truncated and chimeric arrestins. Analysis of the binding characteristics of the various mutant arrestins suggests a common molecular mechanism involved in determining receptor binding selectivity. Structural elements that contribute to arrestin binding include: 1) a C-terminal acidic region that serves a regulatory role in controlling arrestin binding selectivity toward the phosphorylated and activated form of a receptor, without directly participating in receptor interaction; 2) a basic N-terminal domain that directly participates in receptor interaction and appears to serve a regulatory role via intramolecular interaction with the C-terminal acidic region; and 3) two centrally localized domains that are directly involved in determining receptor binding specificity and selectivity. A comparative structure-function model of all arrestins and a kinetic model of beta-arrestin and arrestin 3 interaction with receptors are proposed.

  2. Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry

    SciTech Connect

    Yun, Youngjoo; Kim, Dong Kyun; Seo, Min-Duk; Kim, Kyeong-Man; Chung, Ka Young

    2015-01-30

    Highlights: • The conformational dynamics of β-arrestin1 or β-arrestin2 were analyzed by HDX-MS. • β-Strands II through IV were more dynamic in β-arrestin2 than in β-arrestin1. • The middle loop was less dynamic in β-arrestin2 than in β-arrestin1. • Upon pre-activation by the R169E mutation, β-arrestins became more dynamic. • Pre-activation affected a wider region of β-arrestin1 compared to β-arrestin2. - Abstract: Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. There have been four arrestins identified: arrestin1, arrestin2 (e.g. β-arrestin1), arrestin3 (e.g. β-arrestin2), and arrestin4. β-Arrestin1 and β-arrestin2 are ubiquitously expressed and regulate a broad range of GPCRs, while arrestin1 and arrestin4 are expressed in the visual system. Although the functions of β-arrestin1 and β-arrestin2 widely overlap, β-arrestin2 has broader receptor selectivity, and a few studies have suggested that β-arrestin1 and β-arrestin2 have distinct cellular functions. Here, we compared the conformational dynamics of β-arrestin1 and β-arrestin2 by hydrogen/deuterium exchange mass spectrometry (HDX-MS). We also used the R169E mutant as a pre-activation model system. HDX-MS data revealed that β-strands II through IV were more dynamic in β-arrestin2 in the basal state, while the middle loop was more dynamic in β-arrestin1. With pre-activation, both β-arrestin1 and β-arrestin2 became more flexible, but broader regions of β-arrestin1 became flexible compared to β-arrestin2. The conformational differences between β-arrestin1 and β-arrestin2 in both the basal and pre-activated states might determine their different receptor selectivities and different cellular functions.

  3. The effect of phosphorylation on arrestin-rhodopsin interaction in the squid visual system.

    PubMed

    Robinson, Kelly A; Ou, Wei-Lin; Guan, Xinyu; Sugamori, Kim S; Bandyopadhyay, Abhishek; Ernst, Oliver P; Mitchell, Jane

    2015-12-01

    Invertebrate visual opsins are G protein-coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to Gq and activation of phospholipase C. Squid rhodopsin kinase (SQRK) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein-coupled receptor kinases. The sites and role of arrestin phosphorylation by SQRK were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C-terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (Kd 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3- to 5-fold (Kd 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for SQRK in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system. Invertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C-terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation.

  4. Glucocorticoids regulate arrestin gene expression and redirect the signaling profile of G protein-coupled receptors.

    PubMed

    Oakley, Robert H; Revollo, Javier; Cidlowski, John A

    2012-10-23

    G protein-coupled receptors (GPCRs) compose the largest family of cell surface receptors and are the most common target of therapeutic drugs. The nonvisual arrestins, β-arrestin-1 and β-arrestin-2, are multifunctional scaffolding proteins that play critical roles in GPCR signaling. On binding of activated GPCRs at the plasma membrane, β-arrestins terminate G protein-dependent responses (desensitization) and stimulate β-arrestin-dependent signaling pathways. Alterations in the cellular complement of β-arrestin-1 and β-arrestin-2 occur in many human diseases, and their genetic ablation in mice has severe consequences. Surprisingly, however, the factors that control β-arrestin gene expression are poorly understood. We demonstrate that glucocorticoids differentially regulate β-arrestin-1 and β-arrestin-2 gene expression in multiple cell types. Glucocorticoids act via the glucocorticoid receptor (GR) to induce the synthesis of β-arrestin-1 and repress the expression of β-arrestin-2. Glucocorticoid-dependent regulation involves the recruitment of ligand-activated glucocorticoid receptors to conserved and functional glucocorticoid response elements in intron-1 of the β-arrestin-1 gene and intron-11 of the β-arrestin-2 gene. In human lung adenocarcinoma cells, the increased expression of β-arrestin-1 after glucocorticoid treatment impairs G protein-dependent activation of inositol phosphate signaling while enhancing β-arrestin-1-dependent stimulation of the MAPK pathway by protease activated receptor 1. These studies demonstrate that glucocorticoids redirect the signaling profile of GPCRs via alterations in β-arrestin gene expression, revealing a paradigm for cross-talk between nuclear and cell surface receptors and a mechanism by which glucocorticoids alter the clinical efficacy of GPCR-based drugs.

  5. Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma

    PubMed Central

    Sun, Wu-Yi; Hu, Shan-Shan; Wu, Jing-Jing; Huang, Qiong; Ma, Yang; Wang, Qing-Tong; Chen, Jing-Yu; Wei, Wei

    2016-01-01

    β-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that β-arrestin2 level, but not β-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, β-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. β-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that β-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, β-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that β-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low β-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC. PMID:27759077

  6. Agonist-Specific Recruitment of Arrestin Isoforms Differentially Modify Delta Opioid Receptor Function

    PubMed Central

    Perroy, Julie; Walwyn, Wendy M.; Smith, Monique L.; Vicente-Sanchez, Ana; Segura, Laura; Bana, Alia; Kieffer, Brigitte L.; Evans, Christopher J.

    2016-01-01

    ) preferentially recruit arrestin 3 and, surprisingly, KO of arrestin 3 produces acute tolerance and impaired receptor resensitization to these agonists. Arrestin 3 is in pre-engaged complexes with the delta opioid receptor at the cell membrane and low-internalizing agonists promote this interaction. This study reveals a novel role for arrestin 3 as a facilitator of receptor resensitization. PMID:27013682

  7. Beta-arrestin-biased ligands at seven-transmembrane receptors.

    PubMed

    Violin, Jonathan D; Lefkowitz, Robert J

    2007-08-01

    Seven-transmembrane receptors (7TMRs), the most common molecular targets of modern drug therapy, are critically regulated by beta-arrestins, which both inhibit classic G-protein signaling and initiate distinct beta-arrestin signaling. The interplay of G-protein and beta-arrestin signals largely determines the cellular consequences of 7TMR-targeted drugs. Until recently, a drug's efficacy for beta-arrestin recruitment was believed to be proportional to its efficacy for G-protein activities. This paradigm restricts 7TMR drug effects to a linear spectrum of responses, ranging from inhibition of all responses to stimulation of all responses. However, it is now clear that 'biased ligands' can selectively activate G-protein or beta-arrestin functions and thus elicit novel biological effects from even well-studied 7TMRs. Here, we discuss the current state of beta-arrestin-biased ligand research and the prospects for beta-arrestin bias as a therapeutic target. Consideration of ligand bias might have profound influences on the way scientists approach 7TMR-targeted drug discovery.

  8. The emerging roles of β-arrestins in fibrotic diseases

    PubMed Central

    Gu, Yuan-jing; Sun, Wu-yi; Zhang, Sen; Wu, Jing-jing; Wei, Wei

    2015-01-01

    β-Arrestins and β-arrestin2 are important adaptor proteins and signal transduction proteins that are mainly involved in the desensitization and internalization of G-protein-coupled receptors. Fibrosis is characterized by accumulation of excess extracellular matrix (ECM) molecules caused by chronic tissue injury. If highly progressive, the fibrotic process leads to organ malfunction and, eventually, death. The incurable lung fibrosis, renal fibrosis and liver fibrosis are among the most common fibrotic diseases. Recent studies show that β-arrestins can activate signaling cascades independent of G-protein activation and scaffold many intracellular signaling networks by diverse types of signaling pathways, including the Hedgehog, Wnt, Notch and transforming growth factor-β pathways, as well as downstream kinases such as MAPK and PI3K. These signaling pathways are involved in the pathological process of fibrosis and fibrotic diseases. This β-arrestin-mediated regulation not only affects cell growth and apoptosis, but also the deposition of ECM, activation of inflammatory response and development of fibrotic diseases. In this review, we survey the involvement of β-arrestins in various signaling pathways and highlight different aspects of their regulation of fibrosis. We also discuss the important roles of β-arrestins in the process of fibrotic diseases by regulating the inflammation and deposit of ECM. It is becoming more evident that targeting β-arrestins may offer therapeutic potential for the treatment of fibrotic diseases. PMID:26388156

  9. Multifaceted role of β-arrestins in inflammation and disease

    PubMed Central

    Sharma, Deepika; Parameswaran, Narayanan

    2015-01-01

    Arrestins are intracellular scaffolding proteins known to regulate a range of biochemical processes including G-protein coupled receptor (GPCR) desensitization, signal attenuation, receptor turnover and downstream signaling cascades. Their roles in regulation of signaling network have lately been extended to receptors outside of the GPCR family, demonstrating their roles as important scaffolding proteins in various physiological processes including proliferation, differentiation, and apoptosis. Recent studies have demonstrated a critical role for arrestins in immunological processes including key functions in inflammatory signaling pathways. In this review, we provide a comprehensive analysis of the different functions of the arrestin family of proteins especially related to immunity and inflammatory diseases. PMID:26378652

  10. Arrestins as regulatory hubs in cancer signalling pathways.

    PubMed

    Enslen, Hervé; Lima-Fernandes, Evelyne; Scott, Mark G H

    2014-01-01

    Non-visual arrestins were initially appreciated for the roles they play in the negative regulation of G protein-coupled receptors through the processes of desensitisation and endocytosis. The arrestins are also now known as protein scaffolding platforms that act downstream of multiple types of receptors, ensuring relevant transmission of information for an appropriate cellular response. They function as regulatory hubs in several important signalling pathways that are often dysregulated in human cancers. Interestingly, several recent studies have documented changes in expression and localisation of arrestins that occur during cancer progression and that correlate with clinical outcome. Here, we discuss these advances and how changes in expression/localisation may affect functional outputs of arrestins in cancer biology.

  11. Structure of an Arrestin2-clathrin Complex Reveals a Novel Clathrin Binding Domain that Modulates Receptor Trafficking

    SciTech Connect

    Kang, D.; Kern, R; Puthenveedu, M; von Zastrow, M; Williams, J; Benovic, J

    2009-01-01

    Non-visual arrestins play a pivotal role as adaptor proteins in regulating the signaling and trafficking of multiple classes of receptors. Although arrestin interaction with clathrin, AP-2, and phosphoinositides contributes to receptor trafficking, little is known about the configuration and dynamics of these interactions. Here, we identify a novel interface between arrestin2 and clathrin through x-ray diffraction analysis. The intrinsically disordered clathrin binding box of arrestin2 interacts with a groove between blades 1 and 2 in the clathrin {beta}-propeller domain, whereas an 8-amino acid splice loop found solely in the long isoform of arrestin2 (arrestin2L) interacts with a binding pocket formed by blades 4 and 5 in clathrin. The apposition of the two binding sites in arrestin2L suggests that they are exclusive and may function in higher order macromolecular structures. Biochemical analysis demonstrates direct binding of clathrin to the splice loop in arrestin2L, whereas functional analysis reveals that both binding domains contribute to the receptor-dependent redistribution of arrestin2L to clathrin-coated pits. Mutagenesis studies reveal that the clathrin binding motif in the splice loop is (L/I){sub 2}GXL. Taken together, these data provide a framework for understanding the dynamic interactions between arrestin2 and clathrin and reveal an essential role for this interaction in arrestin-mediated endocytosis.

  12. One-step purification of a functional, constitutively activated form of visual arrestin.

    PubMed

    Huang, Li; Mao, Xiang; Abdulaev, Najmoutin G; Ngo, Tony; Liu, Wei; Ridge, Kevin D

    2012-03-01

    Desensitization of agonist-activated G protein-coupled receptors (GPCRs) requires phosphorylation followed by the binding of arrestin, a ~48 kDa soluble protein. While crystal structures for the inactive, 'basal' state of various arrestins are available, the conformation of 'activated' arrestin adopted upon interaction with activated GPCRs remains unknown. As a first step towards applying high-resolution structural methods to study arrestin conformation and dynamics, we have utilized the subtilisin prodomain/Profinity eXact™ fusion-tag system for the high-level bacterial expression and one-step purification of wild-type visual arrestin (arrestin 1) as well as a mutant form (R175E) of the protein that binds to non-phosphorylated, light-activated rhodopsin (Rho∗). The results show that both prodomain/Profinity eXact™ fusion-tagged wild-type and R175E arrestins can be expressed to levels approaching 2-3 mg/l in Luria-Bertani media, and that the processed, tag-free mature forms can be purified to near homogeneity using a Bio-Scale™ Mini Profinity eXact™ cartridge on the Profinia™ purification system. Functional analysis of R175E arrestin generated using this approach shows that it binds to non-phosphorylated rhodopsin in a light-dependent manner. These findings should facilitate the structure determination of this 'constitutively activated' state of arrestin 1 as well as the monitoring of conformational changes upon interaction with Rho∗.

  13. Structure and functions of arrestins.

    PubMed Central

    Palczewski, K.

    1994-01-01

    Transmembrane signal transductions in a variety of cell types that mediate signals as diverse as those carried by neurotransmitters, hormones, and sensory signals share basic biochemical mechanisms that include: (1) an extracellular perturbation (neurotransmitter, hormone, odor, light); (2) specific receptors; (3) coupling proteins, such as G proteins; and (4) effector enzymes or ion channels. Parallel to these amplification reactions, receptors are precisely inactivated by mechanisms that involve protein kinases and regulatory proteins called arrestins. The structure and functions of arrestins are the focus of this review. PMID:7833798

  14. β-arrestin-1 contributes to brown fat function and directly interacts with PPARα and PPARγ

    PubMed Central

    Wang, Congcong; Zeng, Xianglu; Zhou, Zhaocai; Zhao, Jian; Pei, Gang

    2016-01-01

    The peroxisome proliferator-activated receptor (PPAR) family plays central roles in brown adipose tissue (BAT) adipogenesis and contributes to body temperature maintenance. The transcriptional activity of PPAR family has been shown to be tightly controlled by cellular signal networks. β-arrestins function as major secondary messengers of G protein-coupled receptors (GPCR) signaling by functional interactions with diverse proteins. Here, we report that β-arrestin-1 knock-out mice show enhanced cold tolerance. We found that β-arrestin-1 directly interacts with PPARα and PPARγ through a LXXXLXXXL motif, while D371 in PPARα and L311/N312/D380 in PPARγ are required for their interactions with β-arrestin-1. Further mechanistic studies showed that β-arrestin-1 promotes PPARα- but represses PPARγ-mediated transcriptional activities, providing potential regulatory pathway for BAT function. PMID:27301785

  15. Arrestins in the cardiovascular system.

    PubMed

    Lymperopoulos, Anastasios; Bathgate, Ashley

    2013-01-01

    Of the four mammalian arrestins, only the β-arrestins (βarrs; Arrestin2 and -3) are expressed throughout the cardiovascular system, where they regulate, as either desensitizers/internalizers or signal transducers, several G-protein-coupled receptors (GPCRs) critical for cardiovascular homeostasis. The cardiovascular roles of βarrs have been delineated at an accelerated pace via a variety of techniques and tools, such as knockout mice, siRNA knockdown, artificial or naturally occurring polymorphic GPCRs, and availability of new βarr "biased" GPCR ligands. This chapter summarizes the current knowledge of cardiovascular arrestin physiology and pharmacology, addressing the individual cardiovascular receptors affected by βarrs in vivo, as well as the individual cell types, tissues, and organs of the cardiovascular system in which βarr effects are exerted; for example, cardiac myocyte or fibroblast, vascular smooth muscle, adrenal gland and platelet. In the broader scope of cardiovascular βarr pharmacology, a discussion of the βarr "bias" of certain cardiovascular GPCR ligands is also included.

  16. beta-Arrestins facilitate ubiquitin-dependent degradation of apoptosis signal-regulating kinase 1 (ASK1) and attenuate H2O2-induced apoptosis.

    PubMed

    Zhang, Zhengping; Hao, Jiaying; Zhao, Zhihui; Ben, Peiling; Fang, Fang; Shi, Lijun; Gao, Yanhong; Liu, Junhong; Wen, Chuanjun; Luo, Lan; Yin, Zhimin

    2009-07-01

    beta-Arrestins are ubiquitously expressed proteins that play important roles in receptor desensitization, endocytosis, proteosomal degradation, apoptosis and signaling. It has been reported that beta-Arrestin2 acts as a scaffold by directly interacting with the JNK3 isoform and recruiting MKK4 and the apoptosis-signaling kinase-1 (ASK1). Here, we report a novel function of beta-Arrestins in regulating H(2)O(2)-induced apoptosis. Our study demonstrates that beta-Arrestins physically associate with C-terminal domain of ASK1, and moreover, both over-expression and RNA interference (RNAi) experiments indicate that beta-Arrestins down-regulate ASK1 protein. In detail, beta-Arrestin-induced reduction of ASK1 protein is due to ubiquitination and proteasome-dependent degradation of ASK1 in response to association of beta-Arrestins and ASK1. Upon H(2)O(2) stimulation, the protein binding between beta-Arrestins and ASK1 increases and ASK1 degradation is expedited. In consequence, beta-Arrestins prevent ASK1-JNK signaling and as a result attenuate H(2)O(2)-induced apoptosis. Structurally, C-terminal domain of ASK1 is essential for beta-Arrestins and ASK1 association. We also found that CHIP is required for beta-Arrestins-induced ASK1 degradation, which suggested that beta-Arrestins function as a scaffold of ASK1 and CHIP, leading to CHIP-mediated ASK1 degradation. All these findings indicate that beta-Arrestins play a negative regulatory role in H(2)O(2)-induced apoptosis signaling through associating with ASK1 and CHIP and facilitating ASK1 degradation, which provides a new insight for analyzing the effects of beta-Arrestins on protecting cells from oxidative stress-induced apoptosis.

  17. Mechanisms of Biased β-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor

    PubMed Central

    Delgado-Peraza, Francheska; Ahn, Kwang H.; Nogueras-Ortiz, Carlos; Mungrue, Imran N.; Mackie, Ken; Kendall, Debra A.

    2016-01-01

    Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of β-arrestin-mediated signaling is still very limited. Here we provide a comprehensive view of β-arrestin-mediated signaling from the cannabinoid 1 receptor (CB1R). By using a signaling biased receptor, we define the cascades, specific receptor kinases, and molecular mechanism underlying β-arrestin-mediated signaling: We identify the interaction kinetics of CB1R and β-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of β-arrestin-mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control β-arrestin-mediated signaling. PMID:27009233

  18. The Chemokine Receptor CCR1 Is Constitutively Active, Which Leads to G Protein-independent, β-Arrestin-mediated Internalization*

    PubMed Central

    Gilliland, C. Taylor; Salanga, Catherina L.; Kawamura, Tetsuya; Trejo, JoAnn; Handel, Tracy M.

    2013-01-01

    Activation of G protein-coupled receptors by their associated ligands has been extensively studied, and increasing structural information about the molecular mechanisms underlying ligand-dependent receptor activation is beginning to emerge with the recent expansion in GPCR crystal structures. However, some GPCRs are also able to adopt active conformations in the absence of agonist binding that result in the initiation of signal transduction and receptor down-modulation. In this report, we show that the CC-type chemokine receptor 1 (CCR1) exhibits significant constitutive activity leading to a variety of cellular responses. CCR1 expression is sufficient to induce inhibition of cAMP formation, increased F-actin content, and basal migration of human and murine leukocytes. The constitutive activity leads to basal phosphorylation of the receptor, recruitment of β-arrestin-2, and subsequent receptor internalization. CCR1 concurrently engages Gαi and β-arrestin-2 in a multiprotein complex, which may be accommodated by homo-oligomerization or receptor clustering. The data suggest the presence of two functional states for CCR1; whereas receptor coupled to Gαi functions as a canonical GPCR, albeit with high constitutive activity, the CCR1·β-arrestin-2 complex is required for G protein-independent constitutive receptor internalization. The pertussis toxin-insensitive uptake of chemokine by the receptor suggests that the CCR1·β-arrestin-2 complex may be related to a potential scavenging function of the receptor, which may be important for maintenance of chemokine gradients and receptor responsiveness in complex fields of chemokines during inflammation. PMID:24056371

  19. Beta-Arrestin1 Levels in Mononuclear Leukocytes Support Depression Scores for Women with Premenstrual Dysphoric Disorder

    PubMed Central

    Alam, Farzana; Nayyar, Sanket; Richie, William; Archibong, Anthony; Nayyar, Tultul

    2015-01-01

    Depression is very common in reproductive women particularly with premenstrual dysphoric disorder (PMDD), which is a severe form of premenstrual syndrome (PMS). Beta-arrestins were previously implicated in the pathophysiology, diagnosis and treatment for mood disorders. This study examined whether a measurement for beta-arrestin1 levels in peripheral blood mononuclear leukocytes (PBMC), could aid to distinguish between PMDD and PMS. Study participants (n = 25) were non-pregnant women between 18–42 years of age with the symptoms of PMS/PMDD, but not taking any antidepressants/therapy and at the luteal phase of menstruation. The levels of beta-arrestin1 protein in the PBMCs were determined by ELISA using human beta-arrestin1 kit. The beta-arrestin1 levels were compared with the Hamilton Depression Rating Scale scores among these women. The magnitude of the different parameters for Axis 1 mental disorders were significantly higher and beta arrestin1 protein levels in PBMCs were significantly lower in women with PMDD as compared to PMS women. The reduction in beta arrestin1 protein levels was significantly correlated with the severity of depressive symptoms. Beta-arrestin1 measurements in women may potentially serve for biochemical diagnostic purposes for PMDD and might be useful as evidence-based support for questionnaires. PMID:26703643

  20. Targeting Individual GPCRs with Redesigned Nonvisual Arrestins

    PubMed Central

    Gimenez, Luis E.; Vishnivetskiy, Sergey A.; Gurevich, Vsevolod V.

    2015-01-01

    Numerous human diseases are caused by excessive signaling of mutant G protein-coupled receptors (GPCRs) or receptors that are overstimulated due to upstream signaling imbalances. The feasibility of functional compensation by arrestins with enhanced ability to quench receptor signaling was recently tested in the visual system. The results showed that even in this extremely demanding situation of rods that have no ability to phosphorylate rhodopsin, enhanced arrestin improved rod morphology, light sensitivity, survival, and accelerated photoresponse recovery. Structurally distinct enhanced mutants of arrestins that bind phosphorylated and non-phosphorylated active GPCRs with much higher affinity than parental wild-type (WT) proteins have been constructed. These “super-arrestins” are likely to have the power to dampen the signaling by hyperactive GPCRs. However, most cells express 5–20 GPCR subtypes, only one of which would be overactive, while nonvisual arrestins are remarkably promiscuous, binding hundreds of different GPCRs. Thus, to be therapeutically useful, enhanced versions of nonvisual arrestins must be made fairly specific for particular receptors. Recent identification of very few arrestin residues as key receptor discriminators paves the way to the construction of receptor subtype-specific nonvisual arrestins. PMID:24292829

  1. β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake

    PubMed Central

    Chiang, T; Sansuk, K

    2016-01-01

    Background and Purpose δ Opioid receptor agonists are being developed as potential treatments for depression and alcohol use disorders. This is particularly interesting as depression is frequently co‐morbid with alcohol use disorders. Yet we have previously shown that δ receptor agonists range widely in their ability to modulate alcohol intake; certain δ receptor agonists actually increase alcohol consumption in mice. We propose that variations in β‐arrestin 2 recruitment contribute to the differential behavioural profile of δ receptor agonists. Experimental Approach We used three diarylmethylpiperazine‐based non‐peptidic δ receptor selective agonists (SNC80, SNC162 and ARM390) and three structurally diverse δ receptor agonists (TAN‐67, KNT127 and NIH11082). We tested these agonists in cAMP and β‐arrestin 2 recruitment assays and a behavioural assay of alcohol intake in male C57BL/6 mice. We used β‐arrestin 2 knockout mice and a model of depression‐like behaviour to further study the role of β‐arrestin 2 in δ receptor pharmacology. Key Results All six tested δ receptor agonists were full agonists in the cAMP assay but displayed distinct β‐arrestin 2 recruitment efficacy. The efficacy of δ receptor agonists to recruit β‐arrestin 2 positively correlated with their ability to increase alcohol intake (P < 0.01). The effects of the very efficacious recruiter SNC80 on alcohol intake, alcohol place preference and depression‐like behaviour were β‐arrestin 2‐dependent. Conclusions and Implications Our finding that δ receptor agonists that strongly recruit β‐arrestin 2 can increase alcohol intake carries important ramifications for drug development of δ receptor agonists for treatment of alcohol use disorders and depressive disorders. © 2015 The British Pharmacological Society PMID:26507558

  2. Trout red blood cell arrestin (TRCarr), a novel member of the arrestin family: cloning, immunoprecipitation and expression of recombinant TRCarr.

    PubMed

    Jahns, R; Borgese, F; Lindenthal, S; Straub, A; Motais, R; Fiévet, B

    1996-06-01

    Arrestins are cytosolic proteins involved in the desensitization of G-protein-coupled receptors. We report the cloning of trout red blood cell arrestin which shows 76, 82 and 52% identity with bovine beta-arrestin1, beta-arrestin2 and retinal arrestin respectively. Antibodies were generated against the C-terminus of trout red blood cell arrestin. These antibodies detected arrestin in erythrocyte cytosol and were able to precipitate the native protein. The Na+/H+ antiporter of trout red blood cell is activated by beta-adrenergic stimulation and is then desensitized whereas the transmembrane signalling pathway is not. To investigate the subcellular distribution of arrestin on beta-adrenergic activation and desensitization of the antiporter, precipitation experiments were carried out on trout erythrocytes. A desensitization-dependent shift in cytosolic arrestin to the membranes could not be detected using the immunoprecipitation technique but we cannot exclude the possibility that a small number of cytosolic arrestins might be involved in the regulation of membrane proteins in trout erythrocyte. Recombinant trout arrestin was produced in a protease-deficient Escherichia coli strain and its functionality was tested in a reconstituted rhodopsin assay. The recombinant protein provides a suitable tool for investigating the target for arrestin in trout red blood cell, which still remains to be identified.

  3. Beta-arrestin biased agonism/antagonism at cardiovascular seven transmembrane-spanning receptors.

    PubMed

    Lymperopoulos, Anastasios

    2012-01-01

    Heptahelical, G protein-coupled or seven transmembrane-spanning receptors, such as the β-adrenergic and the angiotensin II type 1 receptors, are the most diverse and therapeutically important family of receptors in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by phosphorylation of the agonist-bound receptor by the G-protein coupled receptor kinases (GRKs), followed by βarrestin binding, which uncouples the phosphorylated receptor from the G protein and subsequently targets the receptor for internalization. As the receptor-βarrestin complex enters the cell, βarrestin-1 and -2, the two mammalian βarrestin isoforms, serve as ligand-regulated scaffolds that recruit a host of intracellular proteins and signal transducers, thus promoting their own wave of signal transduction independently of G-proteins. A constantly increasing number of studies over the past several years have begun to uncover specific roles played by these ubiquitously expressed receptor adapter proteins in signal transduction of several important heptahelical receptors regulating the physiology of various organs/ systems, including the cardiovascular (CV) system. Thus, βarrestin-dependent signaling has increasingly been implicated in CV physiology and pathology, presenting several exciting opportunities for therapeutic intervention in the treatment of CV disorders. Additionally, the discovery of this novel mode of heptahelical receptor signaling via βarrestins has prompted a revision of classical pharmacological concepts such as receptor agonism/antagonism, as well as introduction of new terms such as "biased signaling", which refers to ligand-specific activation of selective signal transduction pathways by the very same receptor. The

  4. Transduction of group I mGluR-mediated synaptic plasticity by β-arrestin2 signalling

    PubMed Central

    Eng, Andrew G.; Kelver, Daniel A.; Hedrick, Tristan P.; Swanson, Geoffrey T.

    2016-01-01

    Conventional signalling by the group I metabotropic glutamate receptors, mGluR1 and mGluR5, occurs through G-protein coupling, but evidence suggests they might also utilize other, non-canonical effector pathways. Here we test whether group I mGluRs require β-arrestin signalling during specific forms of plasticity at hippocampal excitatory synapses. We find that genetic ablation of β-arrestin2, but not β-arrestin1, results in deficits in plasticity mediated by mGlu1 receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal neurons. Pharmacological studies additionally support roles for Src kinases and MAPK/ERK downstream of β-arrestin2 in CA3 neurons. mGluR1 modulation of intrinsic conductances is otherwise preserved in β-arrestin2−/− mice with the exception of a rebound depolarization, and non-mGluR-mediated long-term potentiation is unaltered. These results reveal a signalling pathway engaged by group I mGluRs to effect changes in synaptic and cell intrinsic physiology dependent upon β-arrestin rather than G proteins. Pharmacological manipulation of mGluRs with effector-biased ligands could lead to novel therapies to treat neurological disease. PMID:27886171

  5. Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5.

    PubMed

    Venuti, Assunta; Pastori, Claudia; Pennisi, Rosamaria; Riva, Agostino; Sciortino, Maria Teresa; Lopalco, Lucia

    2016-12-23

    CCR5 stimulation with natural ligands, such as RANTES, classically induces short-term internalization with transient activation of β-arrestins and rapidly recycling on the cell surface. Here we discovered that, in T cells, natural CCR5 antibodies induce a CCR5-negative phenotype with the involvement of β-arrestin2, which leads to the formation of a stable CCR5 signalosome with both β-arrestin2 and ERK1. The activation of β-arrestin2 is necessary to CCR5 signaling for the signalosome formation and stabilization. When all stimuli were washed out, β-arrestin1 silencing favors the activity of β-arrestin2 for the CCR5 signalosome retention. Interestingly, CCR5 turn from Class A trafficking pattern, normally used for its internalization with natural modulating molecules (i.e. RANTES), into a long lasting Class B type specifically induced by stimulation with natural anti-CCR5 antibodies. This new CCR5 pathway is relevant not only to study in depth the molecular basis of all pathologies where CCR5 is involved but also to generate new antidody-based therapeutics.

  6. An Opioid Agonist that Does Not Induce μ-Opioid Receptor—Arrestin Interactions or Receptor Internalization

    PubMed Central

    Groer, C. E.; Tidgewell, K.; Moyer, R. A.; Harding, W. W.; Rothman, R. B.; Prisinzano, T. E.; Bohn, L. M.

    2013-01-01

    G protein-coupled receptor desensitization and trafficking are important regulators of opioid receptor signaling that can dictate overall drug responsiveness in vivo. Furthermore, different μ-opioid receptor (μOR) ligands can lead to varying degrees of receptor regulation, presumably because of distinct structural conformations conferred by agonist binding. For example, morphine binding produces a μOR with low affinity for β-arrestin proteins and limited receptor internalization, whereas enkephalin analogs promote robust trafficking of both β-arrestins and the receptors. Here, we evaluate μOR trafficking in response to activation by a novel μ-selective agonist derived from the naturally occurring plant product, salvinorin A. It is interesting that this compound, termed herkinorin, does not promote the recruitment of β-arrestin-2 to the μOR and does not lead to receptor internalization. Moreover, whereas G protein-coupled receptor kinase overexpression can promote morphine-induced β-arrestin interactions and μOR internalization, such manipulations do not promote herkinorin-induced trafficking. Studies in mice have shown that β-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression. Therefore, drugs that can activate the receptor without recruiting the arrestins may be a promising step in the development of opiate analgesics that distinguish between agonist activity and receptor regulation and may ultimately lead to therapeutics designed to provide pain relief without the adverse side effects normally associated with the opiate narcotics. PMID:17090705

  7. Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5

    PubMed Central

    Venuti, Assunta; Pastori, Claudia; Pennisi, Rosamaria; Riva, Agostino; Sciortino, Maria Teresa; Lopalco, Lucia

    2016-01-01

    CCR5 stimulation with natural ligands, such as RANTES, classically induces short-term internalization with transient activation of β-arrestins and rapidly recycling on the cell surface. Here we discovered that, in T cells, natural CCR5 antibodies induce a CCR5-negative phenotype with the involvement of β-arrestin2, which leads to the formation of a stable CCR5 signalosome with both β-arrestin2 and ERK1. The activation of β-arrestin2 is necessary to CCR5 signaling for the signalosome formation and stabilization. When all stimuli were washed out, β-arrestin1 silencing favors the activity of β-arrestin2 for the CCR5 signalosome retention. Interestingly, CCR5 turn from Class A trafficking pattern, normally used for its internalization with natural modulating molecules (i.e. RANTES), into a long lasting Class B type specifically induced by stimulation with natural anti-CCR5 antibodies. This new CCR5 pathway is relevant not only to study in depth the molecular basis of all pathologies where CCR5 is involved but also to generate new antidody-based therapeutics. PMID:28008933

  8. Beta-arrestin and arrestin are recognized by autoantibodies in sera from multiple sclerosis patients.

    PubMed Central

    Ohguro, H; Chiba, S; Igarashi, Y; Matsumoto, H; Akino, T; Palczewski, K

    1993-01-01

    Multiple sclerosis (MS), one of the most common chronic neurologic diseases, is characterized by the presence of multiple plaques of demyelination throughout the central nervous system. Although the etiology of the disease has not been established, it is believed to involve autoimmune mechanisms. We have examined sera from patients with MS for the presence of antibodies to antigens from brain and retina. Immunoblot analysis of soluble fraction of proteins from bovine brain revealed a prominent band at 45 kDa stained with sera of 8-14 patients with MS. In two patients with MS, serum antibody titers during relapse were higher compared with those when the patients were in remission. These antibodies were undetectable in cerebrospinal fluid of our MS patients and additionally were absent in sera of patients with other neurological diseases and normal control subjects. Furthermore, immunoblot analysis of the soluble fraction from bovine retinal rod outer segments revealed a prominent protein band at 48 kDa stained with MS sera. This antigen was purified to homogeneity from bovine retinal outer segments and identified as arrestin. Additionally, sera from MS patients reacted with purified beta-arrestin 1, a 45-kDa protein homologous to arrestin that is found in various tissues. Using limited proteolysis of arrestin and a competitive ELISA test with a synthetic peptide, we identified the recognition site(s) for antibodies in sera of MS patients at a dominant immunogenic site on arrestin located at the C-terminal region of the molecule. We suggest that the presence of circulating antibodies reactive with beta-arrestin or arrestin may be related to the course of MS progression. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8475065

  9. miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats

    PubMed Central

    Wang, Jian; Xu, Wei; Zhong, Tao; Song, Zongbin; Zou, Yu; Ding, Zhuofeng; Guo, Qulian; Dong, Xinzhong; Zou, Wangyuan

    2016-01-01

    Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. Non-coding microRNAs (miRNAs) modulate gene expression in a post transcriptional manner, and their dysregulation causes various diseases. However, the significance of miRNAs in morphine tolerance is still poorly understood. In the present study, we hypothesized that microRNA-365 (miR-365) is a key functional small RNA that reverses morphine tolerance through regulation of β-arrestin 2 in rats. Here, microarray analysis and quantitative real-time PCR showed that miR-365 was robustly decreased in the spinal cord after chronic morphine administration. In situ hybridization and immunochemistry double staining showed that miR-365 was expressed in neurons of the spinal cord. We identified β-arrestin 2 as the target gene of miR-365 by bioinformatics analysis and luciferase reporter assay. The data showed that overexpression of miR-365 prevented and reversed established morphine tolerance, and increased expression of miR-365 caused a decrease in expression of β-arrestin 2 protein. miR-365 downregulation is involved in the development and maintenance of morphine tolerance through regulation of β-arrestin 2, and miR-365 upregulation provides a promising and novel approach for treatment of morphine tolerance. PMID:27922111

  10. β-Arrestin Regulates Estradiol Membrane-Initiated Signaling in Hypothalamic Neurons

    PubMed Central

    Wong, Angela M.; Abrams, Matthew C.; Micevych, Paul E.

    2015-01-01

    Estradiol (E2) action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS). E2 regulates membrane estrogen receptor-α (ERα) levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH), membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2) in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN) into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001). These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity. PMID:25803606

  11. Internalization of Heterologous Sugar Transporters by Endogenous α-Arrestins in the Yeast Saccharomyces cerevisiae

    PubMed Central

    Sen, Arpita; Acosta-Sampson, Ligia; Alvaro, Christopher G.; Ahn, Jonathan S.; Cate, Jamie H. D.

    2016-01-01

    ABSTRACT When expressed in Saccharomyces cerevisiae using either of two constitutive yeast promoters (PGK1prom and CCW12prom), the transporters CDT-1 and CDT-2 from the filamentous fungus Neurospora crassa are able to catalyze, respectively, active transport and facilitated diffusion of cellobiose (and, for CDT-2, also xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed from the plasma membrane by clathrin-mediated endocytosis and are marked for internalization through ubiquitinylation catalyzed by Rsp5, a HECT class ubiquitin:protein ligase (E3). Recruitment of Rsp5 to specific targets is mediated by a 14-member family of endocytic adaptor proteins, termed α-arrestins. Here we demonstrate that CDT-1 and CDT-2 are subject to α-arrestin-mediated endocytosis, that four α-arrestins (Rod1, Rog3, Aly1, and Aly2) are primarily responsible for this internalization, that the presence of the transport substrate promotes transporter endocytosis, and that, at least for CDT-2, residues located in its C-terminal cytosolic domain are necessary for its efficient endocytosis. Both α-arrestin-deficient cells expressing CDT-2 and otherwise wild-type cells expressing CDT-2 mutants unresponsive to α-arrestin-driven internalization exhibit an increased level of plasma membrane-localized transporter compared to that of wild-type cells, and they grow, utilize the transport substrate, and generate ethanol anaerobically better than control cells. IMPORTANCE Ethanolic fermentation of the breakdown products of plant biomass by budding yeast Saccharomyces cerevisiae remains an attractive biofuel source. To achieve this end, genes for heterologous sugar transporters and the requisite enzyme(s) for subsequent metabolism have been successfully expressed in this yeast. For one of the heterologous transporters examined in this study, we found that the amount of this protein residing in the plasma membrane was the rate-limiting factor for utilization of the cognate

  12. Deficiency of β-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell differentiation

    PubMed Central

    Li, Juan; Wei, Bin; Guo, Ao; Liu, Chang; Huang, Shichao; Du, Fang; Fan, Wei; Bao, Chunde; Pei, Gang

    2013-01-01

    Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (TH17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator β-arrestin1 was significantly up-regulated in peripheral and synovial CD4+ T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of β-arrestin1 ameliorated disease with decreased TH17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that β-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for TH17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for β-arrestin1 in the pathogenesis of collagen-induced arthritis and TH17 cell differentiation and suggest β-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA. PMID:23589893

  13. Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis.

    PubMed

    Zhou, Zheng; Liao, Jun-Ming; Zhang, Peng; Fan, Jun-Bao; Chen, Jie; Liang, Yi

    2011-11-01

    Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.

  14. Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation*

    PubMed Central

    Jean-Charles, Pierre-Yves; Zhang, Lisheng; Wu, Jiao-Hui; Han, Sang-oh; Brian, Leigh; Freedman, Neil J.; Shenoy, Sudha K.

    2016-01-01

    Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin-specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein β-arrestin2. Although β-arrestin2 effects on TRAF6 suggest an anti-inflammatory role, physiologic β-arrestin2 promotes inflammation in atherosclerosis and neointimal hyperplasia. We hypothesized that anti- and proinflammatory dimensions of β-arrestin2 activity could be dictated by β-arrestin2's ubiquitination status, which has been linked with its ability to scaffold and localize activated ERK1/2 to signalosomes. With purified proteins and in intact cells, our protein interaction studies showed that TRAF6/USP20 association and subsequent USP20-mediated TRAF6 deubiquitination were β-arrestin2-dependent. Generation of transgenic mice with smooth muscle cell-specific expression of either USP20 or its catalytically inactive mutant revealed anti-inflammatory effects of USP20 in vivo and in vitro. Carotid endothelial denudation showed that antagonizing smooth muscle cell USP20 activity increased NFκB activation and neointimal hyperplasia. We found that β-arrestin2 ubiquitination was promoted by TLR4 and reversed by USP20. The association of USP20 with β-arrestin2 was augmented when β-arrestin2 ubiquitination was prevented and reduced when β-arrestin2 ubiquitination was rendered constitutive. Constitutive β-arrestin2 ubiquitination also augmented NFκB activation. We infer that pro- and anti-inflammatory activities of β-arrestin2 are determined by β-arrestin2 ubiquitination and that changes in USP20 expression and/or activity can therefore regulate inflammatory responses, at least in part, by defining the ubiquitination

  15. Histamine H2 receptor trafficking: role of arrestin, dynamin, and clathrin in histamine H2 receptor internalization.

    PubMed

    Fernandez, Natalia; Monczor, Federico; Baldi, Alberto; Davio, Carlos; Shayo, Carina

    2008-10-01

    Agonist-induced internalization of G protein-coupled receptors (GPCRs) has been implicated in receptor desensitization, resensitization, and down-regulation. In the present study, we sought to establish whether the histamine H2 receptor (H2r) agonist amthamine, besides promoting receptor desensitization, induced H2r internalization. We further studied the mechanisms involved and its potential role in receptor resensitization. In COS7 transfected cells, amthamine induced H2r time-dependent internalization, showing 70% of receptor endocytosis after 60-min exposure to amthamine. Agonist removal led to the rapid recovery of resensitized receptors to the cell surface. Similar results were obtained in the presence of cycloheximide, an inhibitor of protein synthesis. Treatment with okadaic acid, an inhibitor of the protein phosphatase 2A (PP2A) family of phosphatases, reduced the recovery of both H2r membrane sites and cAMP response. Arrestin 3 but not arrestin 2 overexpression reduced both H2r membrane sites and H2r-evoked cAMP response. Receptor cotransfection with dominant-negative mutants for arrestin, dynamin, Eps15 (a component of the clathrin-mediated endocytosis machinery), or RNA interference against arrestin 3 abolished both H2r internalization and resensitization. Similar results were obtained in U937 cells endogenously expressing H2r. Our findings suggest that amthamine-induced H2r internalization is crucial for H2r resensitization, processes independent of H2r de novo synthesis but dependent on PP2A-mediated dephosphorylation. Although we do not provide direct evidence for H2r interaction with beta-arrestin, dynamin, and/or clathrin, our results support their involvement in H2r endocytosis. The rapid receptor recycling to the cell surface and the specific involvement of arrestin 3 in receptor internalization further suggest that the H2r belongs to class A GPCRs.

  16. Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus.

    PubMed

    Morgenweck, Jenny; Frankowski, Kevin J; Prisinzano, Thomas E; Aubé, Jeffrey; Bohn, Laura M

    2015-12-01

    The kappa opioid receptor (KOR) is involved in mediating pruritus; agonists targeting this receptor have been used to treat chronic intractable itch. Conversely, antagonists induce an itch response at the site of injection. As a G protein-coupled receptor (GPCR), the KOR has potential for signaling via G proteins and βarrestins, however, it is not clear which of these pathways are involved in the KOR modulation of itch. In this study asked whether the actions of KOR in pruritus involve βarrestins by using βarrestin2 knockout (βarr2-KO) mice as well as a recently described biased KOR agonist that biases receptor signaling toward G protein pathways over βarrestin2 recruitment. We find that the KOR antagonists nor-binaltorphimine (NorBNI) and 5'-guanidinonaltrindole (5'GNTI) induce acute pruritus in C57BL/6J mice, with reduced effects in KOR-KO mice. βArr2-KO mice display less of a response to KOR antagonist-induced itch compared to wild types, however no genotype differences are observed from chloroquine phosphate (CP)-induced itch, suggesting that the antagonists may utilize a KOR-βarrestin2 dependent mechanism. The KOR agonist U50,488H was equally effective in both WT and βarr2-KO mice in suppressing CP-induced itch. Furthermore, the G protein biased agonist, Isoquinolinone 2.1 was as effective as U50,488H in suppressing the itch response induced by KOR antagonist NorBNI or CP in C57BL/6J mice. Together these data suggest that the antipruritic effects of KOR agonists may not require βarrestins.

  17. Targeting β-arrestin2 in the treatment of L-DOPA-induced dyskinesia in Parkinson's disease.

    PubMed

    Urs, Nikhil M; Bido, Simone; Peterson, Sean M; Daigle, Tanya L; Bass, Caroline E; Gainetdinov, Raul R; Bezard, Erwan; Caron, Marc G

    2015-05-12

    Parkinson's disease (PD) is characterized by severe locomotor deficits and is commonly treated with the dopamine (DA) precursor l-3,4-dihydroxyphenylalanine (L-DOPA), but its prolonged use causes dyskinesias referred to as L-DOPA-induced dyskinesias (LIDs). Recent studies in animal models of PD have suggested that dyskinesias are associated with the overactivation of G protein-mediated signaling through DA receptors. β-Arrestins desensitize G protein signaling at DA receptors (D1R and D2R) in addition to activating their own G protein-independent signaling events, which have been shown to mediate locomotion. Therefore, targeting β-arrestins in PD L-DOPA therapy might prove to be a desirable approach. Here we show in a bilateral DA-depletion mouse model of Parkinson's symptoms that genetic deletion of β-arrestin2 significantly limits the beneficial locomotor effects while markedly enhancing the dyskinesia-like effects of acute or chronic L-DOPA treatment. Viral rescue or overexpression of β-arrestin2 in knockout or control mice either reverses or protects against LIDs and its key biochemical markers. In other more conventional animal models of DA neuron loss and PD, such as 6-hydroxydopamine-treated mice or rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated nonhuman primates, β-arrestin2 overexpression significantly reduced dyskinesias while maintaining the therapeutic effect of L-DOPA. Considerable efforts are being spent in the pharmaceutical industry to identify therapeutic approaches to block LIDs in patients with PD. Our results point to a potential therapeutic approach, whereby development of either a genetic or pharmacological intervention to enhance β-arrestin2- or limit G protein-dependent D1/D2R signaling could represent a more mechanistically informed strategy.

  18. Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus

    PubMed Central

    Morgenweck, Jenny; Frankowski, Kevin J.; Prisinzano, Thomas E.; Aubé, Jeffrey; Bohn, Laura M.

    2015-01-01

    The kappa opioid receptor (KOR) is involved in mediating pruritus; agonists targeting this receptor have been used to treat chronic intractable itch. Conversely, antagonists induce an inch response at the site of injection. As a G protein-coupled receptor (GPCR), the KOR has potential for signaling via G proteins and βarrestins, however, it is not clear which of these pathways are involved in the KOR modulation of itch. In this study asked whether the actions of KOR in pruritus involve βarrestins by using βarrestin2 knockout (βarr2-KO) mice as well as a recently described biased KOR agonist that biases receptor signaling toward G protein pathways over βarrestin2 recruitment. We find that the KOR antagonists nor-binaltorphimine (NorBNI) and 5′-guanidinonaltrindole (5′GNTI) induce acute pruritus in C57BL/6J mice, with reduced effects in KOR-KO mice. βarr2-KO mice display less of a response to KOR antagonist-induced itch compared to wild types, however no genotype differences are observed from chloroquine phosphate (CP)-induced itch, suggesting that the antagonists may utilize a KOR-βarrestin2 dependent mechanism. The KOR agonist U50,488H was equally effective in both WT and βarr2-KO mice in suppressing CP-induced itch. Furthermore, the G protein biased agonist, Isoquinolinone 2.1 was as effective as U50,488H in suppressing the itch response induced by KOR antagonist NorBNI or CP in C57BL/6J mice. Together these data suggest that the antipruritic effects of KOR agonists may not require βarrestins. PMID:26318102

  19. β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle

    PubMed Central

    Nuber, Susanne; Zabel, Ulrike; Lorenz, Kristina; Nuber, Andreas; Milligan, Graeme; Tobin, Andrew B.; Lohse, Martin J.; Hoffmann, Carsten

    2016-01-01

    (β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs)1–3. They bind to active, phosphorylated GPCRs and thereby shut off ‘classical’ signalling to G proteins3,4, trigger internalization of GPCRs via interaction with the clathrin machinery5–7 and mediate signalling via ‘non-classical’ pathways1,2. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs)1,3,4. The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography8–10. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor–β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling. PMID:27007855

  20. Chromosome mapping of the human arrestin (SAG), {beta}-arrestin 2 (ARRB2), and {beta}-adrenergic receptor kinase 2 (ADRBK2) genes

    SciTech Connect

    Calabrese, G.; Sallese, M.; Stornaiuolo, A.

    1994-09-01

    Two types of proteins play a major role in determining homologous desensitization of G-coupled receptors: {beta}-adrenergic receptor kinase ({beta}ARK), which phosphorylates the agonist-occupied receptor and its functional cofactor, {beta}-arrestin. Both {beta}ARK and {beta}-arrestin are members of multigene families. The family of G-protein-coupled receptor kinases includes rhodopsin kinase, {beta}ARK1, {beta}ARK2, IT11-A (GRK4), GRK5, and GRK6. The arrestin/{beta}-arrestin gene family includes arrestin (also known as S-antigen), {beta}-arrestin 1, and {beta}-arrestin 2. Here we report the chromosome mapping of the human genes for arrestin (SAG), {beta}arrestin 2 (ARRB2), and {beta}ARK2 (ADRBK2) by fluorescence in situ hybridization (FISH). FISH results confirmed the assignment of the gene coding for arrestin (SAG) to chromosome 2 and allowed us to refine its localization to band q37. The gene coding for {beta}-arrestin 2 (ARRB2) was mapped to chromosome 17p13 and that coding for {beta}ARK2 (ADRBK2) to chromosome 22q11. 17 refs., 1 fig.

  1. Prognostic significance of USP33 in advanced colorectal cancer patients: new insights into β-arrestin-dependent ERK signaling

    PubMed Central

    Liu, Hongda; Zhang, Qun; Li, Kangshuai; Gong, Zheng; Liu, Zhaochen; Xu, Yunfei; Swaney, Mary Hannah; Xiao, Kunhong; Chen, Yuxin

    2016-01-01

    Patients with liver metastases of colorectal cancer (CRCLM) have a poorer prognosis compared to colorectal cancer (CRC) patients in local stage. Evaluating the recurrence and overall survival of advanced patients is critical in improving disease treatment and clinical outcome. Here we investigated the expression pattern of USP33, a deubiquitinating enzyme, in both primary CRC tissues and liver metastases tissues. Univariate and multivariate analyses identified that low expression of USP33 in CRCLM tissues indicated high recurrence risk and poor overall prognosis. Overexpression of USP33 can significantly inhibit cell proliferation, migration, and invasion. On the other hand, USP33 knock-down promoted cell proliferation and invasion under SDF-1 stimulation; whereas dynasore (an internalization inhibitor) pretreatment in USP33 silencing cells showed a distinct antipromoting effect, revealing the participation of CXCR4 internalization in regulating tumor progress. Further results verified that USP33 can deubiquitinate β-arrestin2, subsequently block the internalization of SDF-1-stimulated CXCR4, and disrupt β-arrestin-dependent ERK activation. The existence and functions of β-arrestin-dependent signaling have been previously determined in several Gs-coupled receptors, such as β2-adrenergic receptor and angiotensin receptor subtype 1a; however, little is known about this in Gi-coupled receptors. Our study not only established USP33 as a novel prognosis biomarker in advanced CRCLM patients, but also highlighted the significance of β-arrestin-dependent ERK signaling in cancer development. PMID:27835898

  2. The conformational signature of arrestin3 predicts its trafficking and signaling functions

    PubMed Central

    Lee, Mi-Hye; Appleton, Kathryn M.; Strungs, Erik G.; Kwon, Joshua Y.; Morinelli, Thomas A.; Peterson, Yuri K.; Laporte, Stephane A.; Luttrell, Louis M.

    2016-01-01

    Arrestins are cytosolic proteins that regulate G protein-coupled receptor (GPCR) desensitization, internalization, trafficking, and signaling1,2. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets them for internalization via clathrin-coated pits3,4. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G protein effectors into GPCR-based ‘signalsomes’5,6. While the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify divergent arrestin functions is not understood. Using a panel of intramolecular FlAsH-BRET reporters7 to monitor conformational changes in arrestin3, we show here that GPCRs impose distinctive arrestin ‘conformational signatures’ that reflect the stability of the receptor-arrestin complex and role of arrestin3 in activating or dampening downstream signaling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in arrestin3 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average arrestin3 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands8,9 and in identifying factors that dictate arrestin conformation and function. PMID:27007854

  3. GPCRs and arrestins in airways: implications for asthma

    PubMed Central

    Penn, Raymond B.; Bond, Richard A.; Walker, Julia K. L.

    2015-01-01

    The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (β2AR) promotes pro-relaxant signaling in and relaxation of ASM resulting in greater airway patency and reversal of life-threatening bronchoconstriction. In additions, GPCR-mediated functions in other cell types, including airway epithelium and hematopoietic cells, are involved in control of lung inflammation that causes most asthma. The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization, or via G protein-independent signaling, renders arrestins an intriguing therapeutic target for asthma and other obstructive lung diseases. This review will focus on the potential role of arrestins in those GPCR-mediated airway cell functions that are dysregulated in asthma. PMID:24292841

  4. Biased Signaling Favoring Gi over β-Arrestin Promoted by an Apelin Fragment Lacking the C-terminal Phenylalanine*

    PubMed Central

    Ceraudo, Emilie; Galanth, Cécile; Carpentier, Eric; Banegas-Font, Inmaculada; Schonegge, Anne-Marie; Alvear-Perez, Rodrigo; Iturrioz, Xavier; Bouvier, Michel; Llorens-Cortes, Catherine

    2014-01-01

    Apelin plays a prominent role in body fluid and cardiovascular homeostasis. We previously showed that the C-terminal Phe of apelin 17 (K17F) is crucial for triggering apelin receptor internalization and decreasing blood pressure (BP) but is not required for apelin binding or Gi protein coupling. Based on these findings, we hypothesized that the important role of the C-terminal Phe in BP decrease may be as a Gi-independent but β-arrestin-dependent signaling pathway that could involve MAPKs. For this purpose, we have used apelin fragments K17F and K16P (K17F with the C-terminal Phe deleted), which exhibit opposite profiles on apelin receptor internalization and BP. Using BRET-based biosensors, we showed that whereas K17F activates Gi and promotes β-arrestin recruitment to the receptor, K16P had a much reduced ability to promote β-arrestin recruitment while maintaining its Gi activating property, revealing the biased agonist character of K16P. We further show that both β-arrestin recruitment and apelin receptor internalization contribute to the K17F-stimulated ERK1/2 activity, whereas the K16P-promoted ERK1/2 activity is entirely Gi-dependent. In addition to providing new insights on the structural basis underlying the functional selectivity of apelin peptides, our study indicates that the β-arrestin-dependent ERK1/2 activation and not the Gi-dependent signaling may participate in K17F-induced BP decrease. PMID:25012663

  5. Arrestin-3 is essential for the activation of Fyn by the luteinizing hormone receptor (LHR) in MA-10 cells*

    PubMed Central

    Galet, Colette; Ascoli, Mario

    2008-01-01

    Recent studies showed that Fyn is a mediator of the LHR-induced activation of the ERK1/2 cascade in MA-10 cells. Since the LHR is a G protein-coupled receptor and the Src family of kinases can be activated by some Gα subunits and by the non-visual arrestins we investigated the role of these signaling molecules in the LHR-provoked activation of Fyn. Small interfering RNAs (siRNAs) that target two Gα subunits that participate in LHR signaling (Gαs and Gα11) and one that targets arrestin-3 were co-transfected with the hLHR in MA-10 cells. We then determined the effects of these siRNAs on the LHR-provoked activation of Fyn, the phosphorylation of FAK (a prominent Fyn substrate) and the release of EGF-like growth factors (a Fyn-mediated process). Expression of the siRNA against Gαs decreased the level of Gαs and LHR-stimulated cAMP production by ~50% but did not affect LHR-stimulated Fyn activation or FAK phosphorylation. Likewise, expression of the siRNA against Gα11 decreased the level of Gα11 and LHR-stimulated inositol phosphate production by ~50% but did not affect LHR-stimulated Fyn activation or FAK phosphorylation. Expression of the siRNA against arrestin-3 decreased the level of arrestin-3 and the rate of internalization of hCG by ~50% and it also inhibited the LHR-provoked stimulation of Fyn, the phosphorylation of FAK and the release of EGF-like growth factors. These results show that, in MA-10 cells, the hLHR activates Fyn through and arrestin-3-dependent pathway and that this pathway is a mediator of the hLHR-provoked release of EGF-like growth factors. PMID:18647647

  6. Cooling-increased phospho-β-arrestin-1 and β-arrestin-1 expression levels in 3T3-L1 adipocytes.

    PubMed

    Ohsaka, Yasuhito; Nishino, Hoyoku

    2012-08-01

    Cooling induces several responses that are modulated by molecular inhibitors and activators and receptor signaling. Information regarding potential targets involved in cold response mechanisms is still insufficient. We examined levels of the receptor-signaling mediator β-arrestin-1 and phospho-Ser-412 β-arrestin-1 in 3T3-L1 adipocytes exposed to 4-37 °C or treated with some molecular agents at 37°C. We also cooled cells with or without modification and signal-modulating agents. These conditions did not decrease cell viability, and western blot analysis revealed that exposure to 4 °C for 1.5h and to 28 and 32 °C for 24 and 48 h increased phospho-β-arrestin-1 and β-arrestin-1 levels and that exposure to 4 and 18 °C for 3 and 4.5h increased β-arrestin-1 level. Serum removal and rewarming abolished β-arrestin-1 alterations induced by cooling. Mithramycin A (a transcription inhibitor) treatment for 4 and 24h increased the level of β-arrestin-1 but not that of phospho-β-arrestin-1. The level of phospho-β-arrestin-1 was increased by okadaic acid (a phosphatase inhibitor), decreased by epinephrine and aluminum fluoride (receptor-signaling modulators), and unaffected by N-ethylmaleimide (an alkylating agent) at 37 °C. N-Ethylmaleimide and the receptor-signaling modulators did not alter β-arrestin-1 expression at 37 °C but impaired the induction of phospho-β-arrestin-1 at 28 and 32 °C without affecting the induction of β-arrestin-1. We show that cold-induced β-arrestin-1 alterations are partially mimicked by molecular agents and that the responsive machinery for β-arrestin-1 requires serum factors and N-ethylmaleimide-sensitive sites and is linked to rewarming- and receptor signaling-responsive machinery. Our findings provide helpful information for clarifying the cold-responsive machinery for β-arrestin-1 and elucidating low-temperature responses.

  7. Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

    SciTech Connect

    Mirshahi, M. Le Marchand, S.

    2015-05-08

    Aim: Previously, we reported that visual arrestin co-purified with glycolytic enzymes. The aim of this study was to analyze the co-purification of arrestin like proteins (ALP) in bovine cardiac tissues with enolases. Methods: The soluble extract of bovine myocardial tissues from different regions such as left and right atriums and ventricles of the bovine heart (n = 3) was analyzed by ACA-34 gel filtration, immuno-affinity column, SDS-PAGE, ELISA, western blot and a sandwich immune assay for quantification of ALP and sequence analysis. Results: We observed that; 1) The cardiac muscle contained a 50 kDa ALP at a concentration of 751 pg/mg of soluble protein extract, 2) ALP purified, by immunoaffinity, contained alpha-enolase of 48 kDa confirmed by protein sequence analysis; 3) Cardiomyocyte cells exposed to anti arrestin and anti enolase monoclonal antibodies showed decreased proliferation in vitro, 4) High level of autoantibodies were detected by ELISA (3.57% for arrestin and 9.12% for α-enolase) in serum of patients with infarcted heart disease. Conclusion: We suggest a possible interaction between ALP and alpha-enolases yielding a complex that may be involved in the induction of cardiac autoimmune diseases. - Highlights: • We examine a possible interaction between arrestin like protein and alpha-enolases in cardiomyocyte. • We demonstrated the effect of antibodies against arrestin and enolase on cardiomyocyte cell proliferation. • We suggest that this proteins complex may be involved in the induction of cardiac autoimmune diseases.

  8. Phosphorylation of β-arrestin2 at Thr(383) by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs.

    PubMed

    Cassier, Elisabeth; Gallay, Nathalie; Bourquard, Thomas; Claeysen, Sylvie; Bockaert, Joël; Crépieux, Pascale; Poupon, Anne; Reiter, Eric; Marin, Philippe; Vandermoere, Franck

    2017-02-07

    In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a β-arrestin-dependent mechanism, promotes MEK-dependent β-arrestin2 phosphorylation at Thr(383), a necessary step for Erk recruitment to the receptor/β-arrestin complex and Erk activation. Likewise, Thr(383) phosphorylation is involved in β-arrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as β2-adrenergic, FSH and CXCR4 receptors, but does not affect the β-arrestin-independent Erk1/2 activation by 5-HT4 receptor. Collectively, these data show that β-arrestin2 phosphorylation at Thr(383) underlies β-arrestin-dependent Erk1/2 activation by GPCRs.

  9. Phosphorylation of β-arrestin2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs

    PubMed Central

    Cassier, Elisabeth; Gallay, Nathalie; Bourquard, Thomas; Claeysen, Sylvie; Bockaert, Joël; Crépieux, Pascale; Poupon, Anne; Reiter, Eric; Marin, Philippe; Vandermoere, Franck

    2017-01-01

    In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a β-arrestin-dependent mechanism, promotes MEK-dependent β-arrestin2 phosphorylation at Thr383, a necessary step for Erk recruitment to the receptor/β-arrestin complex and Erk activation. Likewise, Thr383 phosphorylation is involved in β-arrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as β2-adrenergic, FSH and CXCR4 receptors, but does not affect the β-arrestin-independent Erk1/2 activation by 5-HT4 receptor. Collectively, these data show that β-arrestin2 phosphorylation at Thr383 underlies β-arrestin-dependent Erk1/2 activation by GPCRs. DOI: http://dx.doi.org/10.7554/eLife.23777.001 PMID:28169830

  10. Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist

    PubMed Central

    Doi, Seira; Mori, Tomohisa; Uzawa, Naoki; Arima, Takamichi; Takahashi, Tomoyuki; Uchida, Masashi; Yawata, Ayaka; Narita, Michiko; Uezono, Yasuhito; Suzuki, Tsutomu

    2016-01-01

    Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. PMID:27317580

  11. The M3-muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner.

    PubMed

    Poulin, Benoit; Butcher, Adrian; McWilliams, Phillip; Bourgognon, Julie-Myrtille; Pawlak, Robert; Kong, Kok Choi; Bottrill, Andrew; Mistry, Sharad; Wess, Jürgen; Rosethorne, Elizabeth M; Charlton, Steven J; Tobin, Andrew B

    2010-05-18

    Degeneration of the cholinergic system is considered to be the underlying pathology that results in the cognitive deficit in Alzheimer's disease. This pathology is thought to be linked to a loss of signaling through the cholinergic M(1)-muscarinic receptor subtype. However, recent studies have cast doubt on whether this is the primary receptor mediating cholinergic-hippocampal learning and memory. The current study offers an alternative mechanism involving the M(3)-muscarinic receptor that is expressed in numerous brain regions including the hippocampus. We demonstrate here that M(3)-muscarinic receptor knockout mice show a deficit in fear conditioning learning and memory. The mechanism used by the M(3)-muscarinic receptor in this process involves receptor phosphorylation because a knockin mouse strain expressing a phosphorylation-deficient receptor mutant also shows a deficit in fear conditioning. Consistent with a role for receptor phosphorylation, we demonstrate that the M(3)-muscarinic receptor is phosphorylated in the hippocampus following agonist treatment and following fear conditioning training. Importantly, the phosphorylation-deficient M(3)-muscarinic receptor was coupled normally to G(q/11)-signaling but was uncoupled from phosphorylation-dependent processes such as receptor internalization and arrestin recruitment. It can, therefore, be concluded that M(3)-muscarinic receptor-dependent learning and memory depends, at least in part, on receptor phosphorylation/arrestin signaling. This study opens the potential for biased M(3)-muscarinic receptor ligands that direct phosphorylation/arrestin-dependent (non-G protein) signaling as being beneficial in cognitive disorders.

  12. Agonist-receptor-arrestin, an alternative ternary complex with high agonist affinity.

    PubMed

    Gurevich, V V; Pals-Rylaarsdam, R; Benovic, J L; Hosey, M M; Onorato, J J

    1997-11-14

    The rapid decrease of a response to a persistent stimulus, often termed desensitization, is a widespread biological phenomenon. Signal transduction by numerous G protein-coupled receptors appears to be terminated by a strikingly uniform two-step mechanism, most extensively characterized for the beta2-adrenergic receptor (beta2AR), m2 muscarinic cholinergic receptor (m2 mAChR), and rhodopsin. The model predicts that activated receptor is initially phosphorylated and then tightly binds an arrestin protein that effectively blocks further G protein interaction. Here we report that complexes of beta2AR-arrestin and m2 mAChR-arrestin have a higher affinity for agonists (but not antagonists) than do receptors not complexed with arrestin. The percentage of phosphorylated beta2AR in this high affinity state in the presence of full agonists varied with different arrestins and was enhanced by selective mutations in arrestins. The percentage of high affinity sites also was proportional to the intrinsic activity of an agonist, and the coefficient of proportionality varies for different arrestin proteins. Certain mutant arrestins can form these high affinity complexes with unphosphorylated receptors. Mutations that enhance formation of the agonist-receptor-arrestin complexes should provide useful tools for manipulating both the efficiency of signaling and rate and specificity of receptor internalization.

  13. Differential β-arrestin2 requirements for constitutive and agonist-induced internalization of the CB1 cannabinoid receptor.

    PubMed

    Gyombolai, Pál; Boros, Eszter; Hunyady, László; Turu, Gábor

    2013-06-15

    CB1 cannabinoid receptor (CB1R) undergoes both constitutive and agonist-induced internalization, but the underlying mechanisms of these processes and the role of β-arrestins in the regulation of CB1R function are not completely understood. In this study, we followed CB1R internalization using confocal microscopy and bioluminescence resonance energy transfer measurements in HeLa and Neuro-2a cells. We found that upon activation CB1R binds β-arrestin2 (β-arr2), but not β-arrestin1. Furthermore, both the expression of dominant-negative β-arr2 (β-arr2-V54D) and siRNA-mediated knock-down of β-arr2 impaired the agonist-induced internalization of CB1R. In contrast, neither β-arr2-V54D nor β-arr2-specific siRNA had a significant effect on the constitutive internalization of CB1R. However, both constitutive and agonist-induced internalization of CB1R were impaired by siRNA-mediated depletion of clathrin heavy chain. We conclude that although clathrin is required for both constitutive and agonist-stimulated internalization of CB1R, β-arr2 binding is only required for agonist-induced internalization of the receptor suggesting that the molecular mechanisms underlying constitutive and agonist-induced internalization of CB1R are different.

  14. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

    DOE PAGES

    Kang, Yanyong; Zhou, X. Edward; Gao, Xiang; ...

    2015-07-22

    G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotationmore » between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. In conclusion, this structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.« less

  15. Formation and Decay of the Arrestin·Rhodopsin Complex in Native Disc Membranes*

    PubMed Central

    Beyrière, Florent; Sommer, Martha E.; Szczepek, Michal; Bartl, Franz J.; Hofmann, Klaus Peter; Heck, Martin; Ritter, Eglof

    2015-01-01

    In the G protein-coupled receptor rhodopsin, light-induced cis/trans isomerization of the retinal ligand triggers a series of distinct receptor states culminating in the active Metarhodopsin II (Meta II) state, which binds and activates the G protein transducin (Gt). Long before Meta II decays into the aporeceptor opsin and free all-trans-retinal, its signaling is quenched by receptor phosphorylation and binding of the protein arrestin-1, which blocks further access of Gt to Meta II. Although recent crystal structures of arrestin indicate how it might look in a precomplex with the phosphorylated receptor, the transition into the high affinity complex is not understood. Here we applied Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1 and phosphorylated rhodopsin in native disc membranes. By isolating the unique infrared signature of arrestin binding, we directly observed the structural alterations in both reaction partners. In the high affinity complex, rhodopsin adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of β-sheet structure indicates an increase in flexibility but is inconsistent with a large scale structural change. During Meta II decay, the arrestin-rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the receptor population in a specific Meta II protein conformation, whereas the other half decays to inactive opsin. Altogether these results illustrate the distinct binding modes used by arrestin to interact with different functional forms of the receptor. PMID:25847250

  16. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

    PubMed Central

    Kang, Yanyong; Zhou, X. Edward; Gao, Xiang; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; Barty, Anton; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Ke, Jiyuan; Eileen Tan, M. H.; Zhang, Chenghai; Moeller, Arne; West, Graham M.; Pascal, Bruce; Van Eps, Ned; Caro, Lydia N.; Vishnivetskiy, Sergey A.; Lee, Regina J.; Suino-Powell, Kelly M.; Gu, Xin; Pal, Kuntal; Ma, Jinming; Zhi, Xiaoyong; Boutet, Sébastien; Williams, Garth J.; Messerschmidt, Marc; Gati, Cornelius; Zatsepin, Nadia A.; Wang, Dingjie; James, Daniel; Basu, Shibom; Roy-Chowdhury, Shatabdi; Conrad, Chelsie; Coe, Jesse; Liu, Haiguang; Lisova, Stella; Kupitz, Christopher; Grotjohann, Ingo; Fromme, Raimund; Jiang, Yi; Tan, Minjia; Yang, Huaiyu; Li, Jun; Wang, Meitian; Zheng, Zhong; Li, Dianfan; Howe, Nicole; Zhao, Yingming; Standfuss, Jörg; Diederichs, Kay; Dong, Yuhui; Potter, Clinton S; Carragher, Bridget; Caffrey, Martin; Jiang, Hualiang; Chapman, Henry N.; Spence, John C. H.; Fromme, Petra; Weierstall, Uwe; Ernst, Oliver P.; Katritch, Vsevolod; Gurevich, Vsevolod V.; Griffin, Patrick R.; Hubbell, Wayne L.; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2015-01-01

    G protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signaling to numerous G protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly, in which rhodopsin uses distinct structural elements, including TM7 and Helix 8 to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotation between the N- and C- domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signaling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology. PMID:26200343

  17. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

    SciTech Connect

    Kang, Yanyong; Zhou, X. Edward; Gao, Xiang; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; Barty, Anton; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Ke, Jiyuan; Tan, M. H. Eileen; Zhang, Chenghai; Moeller, Arne; West, Graham M.; Pascal, Bruce D.; Van Eps, Ned; Caro, Lydia N.; Vishnivetskiy, Sergey A.; Lee, Regina J.; Suino-Powell, Kelly M.; Gu, Xin; Pal, Kuntal; Ma, Jinming; Zhi, Xiaoyong; Boutet, Sébastien; Williams, Garth J.; Messerschmidt, Marc; Gati, Cornelius; Zatsepin, Nadia A.; Wang, Dingjie; James, Daniel; Basu, Shibom; Roy-Chowdhury, Shatabdi; Conrad, Chelsie E.; Coe, Jesse; Liu, Haiguang; Lisova, Stella; Kupitz, Christopher; Grotjohann, Ingo; Fromme, Raimund; Jiang, Yi; Tan, Minjia; Yang, Huaiyu; Li, Jun; Wang, Meitian; Zheng, Zhong; Li, Dianfan; Howe, Nicole; Zhao, Yingming; Standfuss, Jörg; Diederichs, Kay; Dong, Yuhui; Potter, Clinton S.; Carragher, Bridget; Caffrey, Martin; Jiang, Hualiang; Chapman, Henry N.; Spence, John C. H.; Fromme, Petra; Weierstall, Uwe; Ernst, Oliver P.; Katritch, Vsevolod; Gurevich, Vsevolod V.; Griffin, Patrick R.; Hubbell, Wayne L.; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2015-07-22

    G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. In conclusion, this structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

  18. β-Arrestin mediates the Frank-Starling mechanism of cardiac contractility.

    PubMed

    Abraham, Dennis M; Davis, Robert T; Warren, Chad M; Mao, Lan; Wolska, Beata M; Solaro, R John; Rockman, Howard A

    2016-12-13

    The Frank-Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank-Starling relationship is currently known to involve length-dependent enhancement of cardiac myofilament Ca(2+) sensitivity. However, the upstream molecular events that link cellular stretch to the length-dependent myofilament Ca(2+) sensitivity are poorly understood. Because the angiotensin II type 1 receptor (AT1R) and the multifunctional transducer protein β-arrestin have been shown to mediate mechanosensitive cellular signaling, we tested the hypothesis that these two proteins are involved in the Frank-Starling mechanism of the heart. Using invasive hemodynamics, we found that mice lacking β-arrestin 1, β-arrestin 2, or AT1R were unable to generate a Frank-Starling force in response to changes in cardiac volume. Although wild-type mice pretreated with the conventional AT1R blocker losartan were unable to enhance cardiac contractility with volume loading, treatment with a β-arrestin-biased AT1R ligand to selectively activate β-arrestin signaling preserved the Frank-Starling relationship. Importantly, in skinned muscle fiber preparations, we found markedly impaired length-dependent myofilament Ca(2+) sensitivity in β-arrestin 1, β-arrestin 2, and AT1R knockout mice. Our data reveal β-arrestin 1, β-arrestin 2, and AT1R as key regulatory molecules in the Frank-Starling mechanism, which potentially can be targeted therapeutically with β-arrestin-biased AT1R ligands.

  19. Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.

    PubMed

    Bychkov, Evgeny; Zurkovsky, Lilia; Garret, Mika B; Ahmed, Mohamed R; Gurevich, Eugenia V

    2012-01-01

    G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

  20. Distinct Cellular and Subcellular Distributions of G Protein-Coupled Receptor Kinase and Arrestin Isoforms in the Striatum

    PubMed Central

    Bychkov, Evgeny; Zurkovsky, Lilia; Garret, Mika B.; Ahmed, Mohamed R.; Gurevich, Eugenia V.

    2012-01-01

    G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization of G protein-coupled receptors (GPCR). Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling. PMID:23139825

  1. Visualization of arrestin recruitment by a G Protein-Coupled Receptor

    PubMed Central

    Reis, Rosana I.; Huang, Li-Yin; Tripathi-Shukla, Prachi; Qian, Jiang; Li, Sheng; Blanc, Adi; Oleskie, Austin N.; Dosey, Anne M.; Su, Min; Liang, Cui-Rong; Gu, Ling-Ling; Shan, Jin-Ming; Chen, Xin; Hanna, Rachel; Choi, Minjung; Yao, Xiao Jie; Klink, Bjoern U.; Kahsai, Alem W.; Sidhu, Sachdev S.; Koide, Shohei; Penczek, Pawel A.; Kossiakoff, Anthony A.; Jr, Virgil L. Woods; Kobilka, Brian K.; Skiniotis, Georgios; Lefkowitz, Robert J.

    2014-01-01

    G Protein Coupled Receptors (GPCRs) are critically regulated by β-arrestins (βarrs), which not only desensitize G protein signaling but also initiate a G protein independent wave of signaling1-5. A recent surge of structural data on a number of GPCRs, including the β2 adrenergic receptor (β2AR)-G protein complex, has provided novel insights into the structural basis of receptor activation6-11. Lacking however has been complementary information on recruitment of βarrs to activated GPCRs primarily due to challenges in obtaining stable receptor-βarr complexes for structural studies. Here, we devised a strategy for forming and purifying a functional β2AR-βarr1 complex that allowed us to visualize its architecture by single particle negative stain electron microscopy (EM) and to characterize the interactions between β2AR and βarr1 using hydrogen-deuterium exchange mass spectrometry (HDXMS) and chemical cross-linking. EM 2D averages and 3D reconstructions reveal bimodal binding of βarr1 to the β2AR, involving two separate sets of interactions, one with the phosphorylated carboxy-terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of cross-linked residues suggest engagement of the finger loop of βarr1 with the seven-transmembrane core of the receptor. In contrast, focal areas of increased HDX indicate regions of increased dynamics in both N and C domains of βarr1 when coupled to the β2AR. A molecular model of the β2AR-βarr signaling complex was made by docking activated βarr1 and β2AR crystal structures into the EM map densities with constraints provided by HDXMS and cross-linking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented herein provides a framework for better understanding the basis of GPCR regulation by arrestins. PMID:25043026

  2. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

    PubMed Central

    Liu, Chun-Hua; Gong, Zheng; Liang, Zong-Lai; Liu, Zhi-Xin; Yang, Fan; Sun, Yu-Jing; Ma, Ming-Liang; Wang, Yi-Jing; Ji, Chao-Ran; Wang, Yu-Hong; Wang, Mei-Jie; Cui, Fu-Ai; Lin, Amy; Zheng, Wen-Shuai; He, Dong-Fang; Qu, Chang-xiu; Xiao, Peng; Liu, Chuan-Yong; Thomsen, Alex R. B.; Joseph Cahill, Thomas; Kahsai, Alem W.; Yi, Fan; Xiao, Kun-Hong; Xue, Tian; Zhou, Zhuan; Yu, Xiao; Sun, Jin-Peng

    2017-01-01

    Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes. PMID:28181498

  3. Functional map of arrestin binding to phosphorylated opsin, with and without agonist

    PubMed Central

    Peterhans, Christian; Lally, Ciara C. M.; Ostermaier, Martin K.; Sommer, Martha E.; Standfuss, Jörg

    2016-01-01

    Arrestins desensitize G protein-coupled receptors (GPCRs) and act as mediators of signalling. Here we investigated the interactions of arrestin-1 with two functionally distinct forms of the dim-light photoreceptor rhodopsin. Using unbiased scanning mutagenesis we probed the individual contribution of each arrestin residue to the interaction with the phosphorylated apo-receptor (Ops-P) and the agonist-bound form (Meta II-P). Disruption of the polar core or displacement of the C-tail strengthened binding to both receptor forms. In contrast, mutations of phosphate-binding residues (phosphosensors) suggest the phosphorylated receptor C-terminus binds arrestin differently for Meta II-P and Ops-P. Likewise, mutations within the inter-domain interface, variations in the receptor-binding loops and the C-edge of arrestin reveal different binding modes. In summary, our results indicate that arrestin-1 binding to Meta II-P and Ops-P is similarly dependent on arrestin activation, although the complexes formed with these two receptor forms are structurally distinct. PMID:27350090

  4. C-edge loops of arrestin function as a membrane anchor

    PubMed Central

    Lally, Ciara C M.; Bauer, Brian; Selent, Jana; Sommer, Martha E

    2017-01-01

    G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin–receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane, and we show that these interactions are distinct in the pre-complex and high-affinity complex in regard to their conformation and orientation. Our results expand current knowledge of C-edge structure and further illuminate the conformational transitions that occur in arrestin along the pathway to tight receptor binding. PMID:28220785

  5. Herkinorin Analogues with Differential Beta-Arrestin-2 Interactions

    PubMed Central

    Tidgewell, Kevin; Groer, Chad E.; Harding, Wayne W.; Lozama, Anthony; Schmidt, Matthew; Marquam, Alfred; Hiemstra, Jessica; Partilla, John S.; Dersch, Christina M.; Rothman, Richard B.; Bohn, Laura M.; Prisinzano, Thomas E.

    2008-01-01

    Salvinorin A is a psychoactive natural product that has been found to be a potent and selective κ opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent κ opioid receptor signaling yet leads to less receptor downregulation than observed with other κ agonists. Our initial chemical modifications of salvinorin A have yielded one analogue, herkinorin (1c), with high affinity at the μOR. We recently reported that 1c does not promote the recruitment of βarrestin-2 to the μOR or receptor internalization. Here we describe three new derivatives of 1c (3c, 3f, and 3i) with similar properties and one, benzamide 7b, that promotes recruitment of βarrestin-2 to the μOR and receptor internalization. Considering the important role μ opioid receptor regulation plays in determining physiological responsiveness to opioid narcotics, μ opioids derived from salvinorin A may offer a unique template for the development of functionally selective μ opioid receptor ligands with the ability to produce analgesia while limiting adverse side effects. PMID:18380425

  6. South Dakota Social Studies Content Standards.

    ERIC Educational Resources Information Center

    South Dakota State Dept. of Education and Cultural Affairs, Pierre.

    This document presents the South Dakota Content Standards for K-12 Social Studies. The document outlines the four major areas of social studies: history, geography, civics, and economics. Standards are provided for each major area according to grade level, separately for grades K-8 and collectively for grades 9-12. Grade level standards represent…

  7. KISS1R Signals Independently of Gαq/11 and Triggers LH Secretion via the β-Arrestin Pathway in the Male Mouse

    PubMed Central

    Ahow, Maryse; Min, Le; Pampillo, Macarena; Nash, Connor; Wen, Junping; Soltis, Kathleen; Carroll, Rona S.; Glidewell-Kenney, Christine A.; Mellon, Pamela L.; Bhattacharya, Moshmi; Tobet, Stuart A.; Kaiser, Ursula B.

    2014-01-01

    Hypothalamic GnRH is the master regulator of the neuroendocrine reproductive axis, and its secretion is regulated by many factors. Among these is kisspeptin (Kp), a potent trigger of GnRH secretion. Kp signals via the Kp receptor (KISS1R), a Gαq/11-coupled 7-transmembrane–spanning receptor. Until this study, it was understood that KISS1R mediates GnRH secretion via the Gαq/11-coupled pathway in an ERK1/2-dependent manner. We recently demonstrated that KISS1R also signals independently of Gαq/11 via β-arrestin and that this pathway also mediates ERK1/2 activation. Because GnRH secretion is ERK1/2-dependent, we hypothesized that KISS1R regulates GnRH secretion via both the Gαq/11- and β-arrestin–coupled pathways. To test this hypothesis, we measured LH secretion, a surrogate marker of GnRH secretion, in mice lacking either β-arrestin-1 or β-arrestin-2. Results revealed that Kp-dependent LH secretion was significantly diminished relative to wild-type mice (P < .001), thus supporting that β-arrestin mediates Kp-induced GnRH secretion. Based on this, we hypothesized that Gαq/11-uncoupled KISS1R mutants, like L148S, will display Gαq/11-independent signaling. To test this hypothesis, L148S was expressed in HEK 293 cells. and results confirmed that, although strongly uncoupled from Gαq/11, L148S retained the ability to trigger significant Kp-dependent ERK1/2 phosphorylation (P < .05). Furthermore, using mouse embryonic fibroblasts lacking β-arrestin-1 and -2, we demonstrated that L148S-mediated ERK1/2 phosphorylation is β-arrestin–dependent. Overall, we conclude that KISS1R signals via Gαq/11 and β-arrestin to regulate GnRH secretion. This novel and important finding could explain why patients bearing some types of Gαq/11-uncoupled KISS1R mutants display partial gonadotropic deficiency and even a reversal of the condition, idiopathic hypogonadotropic hypogonadism. PMID:25147978

  8. Regulation of mitochondrial oxidative stress by β-arrestins in cultured human cardiac fibroblasts

    PubMed Central

    Philip, Jennifer L.; Razzaque, Md. Abdur; Han, Mei; Li, Jinju; Theccanat, Tiju; Xu, Xianyao; Akhter, Shahab A.

    2015-01-01

    ABSTRACT Oxidative stress in cardiac fibroblasts (CFs) promotes transformation to myofibroblasts and collagen synthesis leading to myocardial fibrosis, a precursor to heart failure (HF). NADPH oxidase 4 (Nox4) is a major source of cardiac reactive oxygen species (ROS); however, mechanisms of Nox4 regulation are unclear. β-arrestins are scaffold proteins that signal in G-protein-dependent and -independent pathways; for example, in ERK activation. We hypothesize that β-arrestins regulate oxidative stress in a Nox4-dependent manner and increase fibrosis in HF. CFs were isolated from normal and failing adult human left ventricles. Mitochondrial ROS/superoxide production was quantitated using MitoSox. β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. Mitochondrial oxidative stress and Nox4 expression in CFs were significantly increased in HF. Nox4 knockdown resulted in inhibition of mitochondrial superoxide production and decreased basal and TGF-β-stimulated collagen and α-SMA expression. CF β-arrestin expression was upregulated fourfold in HF. β-arrestin knockdown in failing CFs decreased ROS and Nox4 expression by 50%. β-arrestin overexpression in normal CFs increased mitochondrial superoxide production twofold. These effects were prevented by inhibition of either Nox or ERK. Upregulation of Nox4 seemed to be a primary mechanism for increased ROS production in failing CFs, which stimulates collagen deposition. β-arrestin expression was upregulated in HF and plays an important and newly identified role in regulating mitochondrial superoxide production via Nox4. The mechanism for this effect seems to be ERK-mediated. Targeted inhibition of β-arrestins in CFs might decrease oxidative stress as well as pathological cardiac fibrosis. PMID:26449263

  9. Analytical Study of Physics Education Websites' Content

    ERIC Educational Resources Information Center

    Elayyan, Shaher R.

    2016-01-01

    The current study is compatible with the scientific mobility in dealing with the Internet as a source of knowledge. It aims to introduce the Physics Education Websites (PEWs) and guide their followers toward the most credibility of them by analyzing their content. The sample consisted of (36) websites which were selected according to specific…

  10. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    PubMed

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH.

  11. Fanpage metrics analysis. "Study on content engagement"

    NASA Astrophysics Data System (ADS)

    Rahman, Zoha; Suberamanian, Kumaran; Zanuddin, Hasmah Binti; Moghavvemi, Sedigheh; Nasir, Mohd Hairul Nizam Bin Md

    2016-08-01

    Social Media is now determined as an excellent communicative tool to connect directly with consumers. One of the most significant ways to connect with the consumers through these Social Networking Sites (SNS) is to create a facebook fanpage with brand contents and to place different posts periodically on these fanpages. In measuring social networking sites' effectiveness, corporate houses are now analyzing metrics in terms of calculating engagement rate, number of comments/share and likings in fanpages. So now, it is very important for the marketers to know the effectiveness of different contents or posts of fanpages in order to increase the fan responsiveness and engagement rate in the fan pages. In the study the authors have analyzed total 1834 brand posts from 17 international brands of Electronics companies. Data of 9 months (From December 2014 to August 2015) have been collected for analyses, which were available online in the Brand' fan pages. An econometrics analysis is conducted using Eviews 9, to determine the impact of different contents on fanpage engagement. The study picked the four most frequently posted content to determine their impact on PTA (people Talking About) metrics and Fanpage engagement activities.

  12. Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR

    PubMed Central

    Yang, Fan; Yu, Xiao; Liu, Chuan; Qu, Chang-Xiu; Gong, Zheng; Liu, Hong-Da; Li, Fa-Hui; Wang, Hong-Mei; He, Dong-Fang; Yi, Fan; Song, Chen; Tian, Chang-Lin; Xiao, Kun-Hong; Wang, Jiang-Yun; Sun, Jin-Peng

    2015-01-01

    Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 ‘reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by 19F-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of β-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific β-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors. PMID:26347956

  13. Monitoring G protein-coupled receptor and β-arrestin trafficking in live cells using enhanced bystander BRET

    PubMed Central

    Namkung, Yoon; Le Gouill, Christian; Lukashova, Viktoria; Kobayashi, Hiroyuki; Hogue, Mireille; Khoury, Etienne; Song, Mideum; Bouvier, Michel; Laporte, Stéphane A.

    2016-01-01

    Endocytosis and intracellular trafficking of receptors are pivotal to maintain physiological functions and drug action; however, robust quantitative approaches are lacking to study such processes in live cells. Here we present new bioluminescence resonance energy transfer (BRET) sensors to quantitatively monitor G protein-coupled receptors (GPCRs) and β-arrestin trafficking. These sensors are based on bystander BRET and use the naturally interacting chromophores luciferase (RLuc) and green fluorescent protein (rGFP) from Renilla. The versatility and robustness of this approach are exemplified by anchoring rGFP at the plasma membrane or in endosomes to generate high dynamic spectrometric BRET signals on ligand-promoted recruitment or sequestration of RLuc-tagged proteins to, or from, specific cell compartments, as well as sensitive subcellular BRET imaging for protein translocation visualization. These sensors are scalable to high-throughput formats and allow quantitative pharmacological studies of GPCR trafficking in real time, in live cells, revealing ligand-dependent biased trafficking of receptor/β-arrestin complexes. PMID:27397672

  14. The Viral G Protein-Coupled Receptor ORF74 Hijacks β-Arrestins for Endocytic Trafficking in Response to Human Chemokines.

    PubMed

    de Munnik, Sabrina M; Kooistra, Albert J; van Offenbeek, Jody; Nijmeijer, Saskia; de Graaf, Chris; Smit, Martine J; Leurs, Rob; Vischer, Henry F

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus-infected cells express the virally encoded G protein-coupled receptor ORF74. Although ORF74 is constitutively active, it binds human CXC chemokines that modulate this basal activity. ORF74-induced signaling has been demonstrated to underlie the development of the angioproliferative tumor Kaposi's sarcoma. Whereas G protein-dependent signaling of ORF74 has been the subject of several studies, the interaction of this viral GPCR with β-arrestins has hitherto not been investigated. Bioluminescence resonance energy transfer experiments demonstrate that ORF74 recruits β-arrestins and subsequently internalizes in response to human CXCL1 and CXCL8, but not CXCL10. Internalized ORF74 traffics via early endosomes to recycling and late endosomes. Site-directed mutagenesis and homology modeling identified four serine and threonine residues at the distal end of the intracellular carboxyl-terminal of ORF74 that are required for β-arrestin recruitment and subsequent endocytic trafficking. Hijacking of the human endocytic trafficking machinery is a previously unrecognized action of ORF74.

  15. The Viral G Protein-Coupled Receptor ORF74 Hijacks β-Arrestins for Endocytic Trafficking in Response to Human Chemokines

    PubMed Central

    de Munnik, Sabrina M.; Kooistra, Albert J.; van Offenbeek, Jody; Nijmeijer, Saskia; de Graaf, Chris; Smit, Martine J.; Leurs, Rob; Vischer, Henry F.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus-infected cells express the virally encoded G protein-coupled receptor ORF74. Although ORF74 is constitutively active, it binds human CXC chemokines that modulate this basal activity. ORF74-induced signaling has been demonstrated to underlie the development of the angioproliferative tumor Kaposi’s sarcoma. Whereas G protein-dependent signaling of ORF74 has been the subject of several studies, the interaction of this viral GPCR with β-arrestins has hitherto not been investigated. Bioluminescence resonance energy transfer experiments demonstrate that ORF74 recruits β-arrestins and subsequently internalizes in response to human CXCL1 and CXCL8, but not CXCL10. Internalized ORF74 traffics via early endosomes to recycling and late endosomes. Site-directed mutagenesis and homology modeling identified four serine and threonine residues at the distal end of the intracellular carboxyl-terminal of ORF74 that are required for β-arrestin recruitment and subsequent endocytic trafficking. Hijacking of the human endocytic trafficking machinery is a previously unrecognized action of ORF74. PMID:25894435

  16. Emerging roles for β-arrestin-1 in the control of the pancreatic β-cell function and mass: new therapeutic strategies and consequences for drug screening.

    PubMed

    Dalle, Stéphane; Ravier, Magalie A; Bertrand, Gyslaine

    2011-03-01

    Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase in β-cell mass, decreased β-cell survival and impaired glucose-dependent insulin release. Pancreatic β-cell proliferation, survival and secretion are thought to be regulated by signalling pathways linked to G-protein coupled receptors (GPCRs), such as the glucagon-like peptide-1 (GLP-1) and the pituitary adenylate cyclase-activating polypeptide (PACAP) receptors. β-arrestin-1 serves as a multifunctional adaptor protein that mediates receptor desensitization, receptor internalization, and links GPCRs to downstream pathways such as tyrosine kinase Src, ERK1/2 or Akt/PKB. Importantly, recent studies found that β-arrestin-1 mediates GLP-1 signalling to insulin secretion, GLP-1 antiapoptotic effect by phosphorylating the proapoptotic protein Bad through ERK1/2 activation, and PACAP potentiation of glucose-induced long-lasting ERK1/2 activation controlling IRS-2 expression. Together, these novel findings reveal an important functional role for β-arrestin-1 in the regulation of insulin secretion and β-cell survival by GPCRs.

  17. β-Arrestin-1 Drives Endothelin-1–Mediated Podocyte Activation and Sustains Renal Injury

    PubMed Central

    Buelli, Simona; Rosanò, Laura; Gagliardini, Elena; Corna, Daniela; Longaretti, Lorena; Pezzotta, Anna; Perico, Luca; Conti, Sara; Rizzo, Paola; Novelli, Rubina; Morigi, Marina; Zoja, Carlamaria; Remuzzi, Giuseppe; Bagnato, Anna

    2014-01-01

    Activation of endothelin-A receptor (ETAR) by endothelin-1 (ET-1) drives epithelial-to-mesenchymal transition in ovarian tumor cells through β-arrestin signaling. Here, we investigated whether this pathogenetic pathway could affect podocyte phenotype in proliferative glomerular disorders. In cultured mouse podocytes, ET-1 caused loss of the podocyte differentiation marker synaptopodin and acquisition of the mesenchymal marker α-smooth muscle actin. ET-1 promoted podocyte migration via ETAR activation and increased β-arrestin-1 expression. Activated ETAR recruited β-arrestin-1 to form a trimeric complex with Src leading to epithelial growth factor receptor (EGFR) transactivation and β-catenin phosphorylation, which promoted gene transcription of Snail. Increased Snail expression fostered ET-1–induced migration as confirmed by Snail knockdown experiments. Silencing of β-arrestin-1 prevented podocyte phenotypic changes and motility and inhibited ETAR-driven signaling. In vitro findings were confirmed in doxorubicin (Adriamycin)-induced nephropathy. Mice receiving Adriamycin developed renal injury with loss of podocytes and hyperplastic lesion formation; β-arrestin-1 expression increased in visceral podocytes and in podocytes entrapped in pseudo-crescents. Administration of the selective ETAR antagonist sitaxsentan prevented podocyte loss, formation of the hyperplastic lesions, and normalized expression of glomerular β-arrestin-1 and Snail. Increased β-arrestin-1 levels in podocytes retrieved from crescents of patients with proliferative glomerulopathies confirmed the translational relevance of these findings and suggest the therapeutic potential of ETAR antagonism for a group of diseases still needing a specific treatment. PMID:24371298

  18. Discovery of ML314, a Brain Penetrant Nonpeptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor

    PubMed Central

    2013-01-01

    The neurotensin 1 receptor (NTR1) is an important therapeutic target for a range of disease states including addiction. A high-throughput screening campaign, followed by medicinal chemistry optimization, led to the discovery of a nonpeptidic β-arrestin biased agonist for NTR1. The lead compound, 2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)-piperazin-1-yl)quinazoline, 32 (ML314), exhibits full agonist behavior against NTR1 (EC50 = 2.0 μM) in the primary assay and selectivity against NTR2. The effect of 32 is blocked by the NTR1 antagonist SR142948A in a dose-dependent manner. Unlike peptide-based NTR1 agonists, compound 32 has no significant response in a Ca2+ mobilization assay and is thus a biased agonist that activates the β-arrestin pathway rather than the traditional Gq coupled pathway. This bias has distinct biochemical and functional consequences that may lead to physiological advantages. Compound 32 displays good brain penetration in rodents, and studies examining its in vivo properties are underway. PMID:24611085

  19. Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo

    PubMed Central

    Martin, Bronwen; Gesty-Palmer, Diane; Cheung, Huey; Johnson, Calvin; Patel, Shamit; Becker, Kevin G.; Wood, William H.; Zhang, Yongqing; Lehrmann, Elin; Luttrell, Louis M.

    2015-01-01

    Biased G protein–coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in cellula efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [d-Trp12, Tyr34]bovine PTH(7-34) in six different murine tissues after chronic drug exposure. We find that [d-Trp12, Tyr34]bovine PTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, human PTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized. PMID:25637603

  20. {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation.

    PubMed

    Ahn, Seungkirl; Kim, Jihee; Hara, Makoto R; Ren, Xiu-Rong; Lefkowitz, Robert J

    2009-03-27

    beta-Arrestins, originally discovered as terminators of G protein-coupled receptor signaling, have more recently been appreciated to also function as signal transducers in their own right, although the consequences for cellular physiology have not been well understood. Here we demonstrate that beta-arrestin-2 mediates anti-apoptotic cytoprotective signaling stimulated by a typical 7-transmembrane receptor the angiotensin ATII 1A receptor, expressed endogenously in rat vascular smooth muscle cells or by transfection in HEK-293 cells. Receptor stimulation leads to concerted activation of two pathways, ERK/p90RSK and PI3K/AKT, which converge to phosphorylate and inactivate the pro-apoptotic protein BAD. Anti-apoptotic effects as well as pathway activities can be stimulated by an angiotensin analog (SII), which has been previously shown to activate beta-arrestin but not G protein-dependent signaling, and are abrogated by beta-arrestin-2 small interfering RNA. These findings establish a key role for beta-arrestin-2 in mediating cellular cytoprotective functions by a 7-transmembrane receptor and define the biochemical pathways involved.

  1. Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through β-arrestin-2 in THP-1 cell line

    SciTech Connect

    Wang, Wei; Zhang, Yuan; Xu, Ming; Zhang, You-Yi; He, Bei

    2015-06-26

    The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β{sub 2}-adrenergic receptor (β{sub 2}-AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β{sub 2}-AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β{sub 2}-AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases. - Highlights: • β{sub 2}-AR agonist fenoterol exerts its protective effect on LPS-treated THP-1 cells. • Fenoterol inhibits LPS-induced AMPK activation and IL-1β production. • β-arrestin2 mediates fenoterol-inhibited AMPK activation and IL-1β release. • AMPKα1 is involved in LPS-induced NF-κB activation and IL-1β production.

  2. Ligand Bias at Metabotropic Glutamate 1a Receptors: Molecular Determinants That Distinguish β-Arrestin-Mediated from G Protein-Mediated Signaling

    PubMed Central

    Emery, Andrew C.; DiRaddo, John O.; Miller, Eric; Hathaway, Hannah A.; Pshenichkin, Sergey; Takoudjou, Guy Rodrigue; Grajkowska, Ewa; Yasuda, Robert P.; Wolfe, Barry B.

    2012-01-01

    The metabotropic glutamate 1a (mGlu1a) receptor is a G protein-coupled receptor linked with phosphoinositide (PI) hydrolysis and with β-arrestin-1-mediated sustained extracellular signal-regulated kinase (ERK) phosphorylation and cytoprotective signaling. Previously, we reported the existence of ligand bias at this receptor, inasmuch as glutamate induced both effects, whereas quisqualate induced only PI hydrolysis. In the current study, we showed that mGlu1 receptor agonists such as glutamate, aspartate, and l-cysteate were unbiased and activated both signaling pathways, whereas quisqualate and (S)-3,5-dihydroxyphenylglycine stimulated only PI hydrolysis. Competitive antagonists inhibited only PI hydrolysis and not the β-arrestin-dependent pathway, whereas a noncompetitive mGlu1 receptor antagonist blocked both pathways. Mutational analysis of the ligand binding domain of the mGlu1a receptor revealed that Thr188 residues were essential for PI hydrolysis but not for protective signaling, whereas Arg323 and Lys409 residues were required for β-arrestin-1-mediated sustained ERK phosphorylation and cytoprotective signaling but not for PI hydrolysis. Therefore, the mechanism of ligand bias appears to involve different modes of agonist interactions with the receptor ligand binding domain. Although some mGlu1a receptor agonists are biased toward PI hydrolysis, we identified two endogenous compounds, glutaric acid and succinic acid, as new mGlu1 receptor agonists that are fully biased toward β-arrestin-mediated protective signaling. Pharmacological studies indicated that, in producing the two effects, glutamate interacted in two distinct ways with mGlu1 receptors, inasmuch as competitive mGlu1 receptor antagonists that blocked PI hydrolysis did not inhibit cytoprotective signaling. Quisqualate, which is biased toward PI hydrolysis, failed to inhibit glutamate-induced protection, and glutaric acid, which is biased toward protection, did not interfere with glutamate

  3. Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes

    PubMed Central

    Zhan, Xuanzhi; Gimenez, Luis E.; Gurevich, Vsevolod V.; Spiller, Benjamin W.

    2011-01-01

    Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. Here we report the first crystal structure of arrestin-3, solved at 3.0Å. Arrestin-3 is an elongated two-domain molecule with the overall fold and key inter-domain interactions that hold free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous β-sheet, consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and -3 we show that the presence of this loose structure correlates with reduced arrestin selectivity for activated receptor, consistent with a conformational change in this β-sheet upon receptor binding. PMID:21215759

  4. Twenty Drosophila visual system cDNA clones: one is a homolog of human arrestin.

    PubMed Central

    Hyde, D R; Mecklenburg, K L; Pollock, J A; Vihtelic, T S; Benzer, S

    1990-01-01

    From a group of 436 Drosophila melanogaster cDNA clones, we selected 39 that are expressed exclusively or predominantly in the adult visual system. By sequence analysis, 20 of the clones appear to represent previously unreported distinct cDNAs. The corresponding transcripts are detected in the retina and optic lobes. The genes are scattered throughout the genome, some near mutations known to affect eye function. One of these clones has been identified, by sequence analysis, as the structural gene (Arr) for a Drosophila homolog of human arrestin. Vertebrate arrestin interacts with rhodopsin in phototransduction and has been associated with an autoimmune form of uveitis in primates. The presence of an arrestin homolog in Drosophila suggests that both the vertebrate and invertebrate phototransduction cascades are regulated in a similar manner. Images PMID:2105491

  5. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex

    SciTech Connect

    Zhou, X. Edward; Gao, Xiang; Barty, Anton; Kang, Yanyong; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Suino-Powell, Kelly M.; Boutet, Sebastien; Williams, Garth J.; Wang, Meitian; Li, Dianfan; Caffrey, Martin; Chapman, Henry N.; Spence, John C. H.; Fromme, Petra; Weierstall, Uwe; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2016-04-12

    Here, serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solved with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes.

  6. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex

    PubMed Central

    Zhou, X. Edward; Gao, Xiang; Barty, Anton; Kang, Yanyong; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Suino-Powell, Kelly M.; Boutet, Sébastien; Williams, Garth J.; Wang, Meitian; Li, Dianfan; Caffrey, Martin; Chapman, Henry N.; Spence, John C.H.; Fromme, Petra; Weierstall, Uwe; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2016-01-01

    Serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solved with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes. PMID:27070998

  7. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex

    NASA Astrophysics Data System (ADS)

    Zhou, X. Edward; Gao, Xiang; Barty, Anton; Kang, Yanyong; He, Yuanzheng; Liu, Wei; Ishchenko, Andrii; White, Thomas A.; Yefanov, Oleksandr; Han, Gye Won; Xu, Qingping; de Waal, Parker W.; Suino-Powell, Kelly M.; Boutet, Sébastien; Williams, Garth J.; Wang, Meitian; Li, Dianfan; Caffrey, Martin; Chapman, Henry N.; Spence, John C. H.; Fromme, Petra; Weierstall, Uwe; Stevens, Raymond C.; Cherezov, Vadim; Melcher, Karsten; Xu, H. Eric

    2016-04-01

    Serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solved with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes.

  8. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

    PubMed

    Singh, Varsha; Aballay, Alejandro

    2012-09-28

    In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

  9. PGE2 Inhibits IL-10 Production via EP2-Mediated β-Arrestin Signaling in Neuroinflammatory Condition.

    PubMed

    Chu, Chun-Hsien; Chen, Shih-Heng; Wang, Qingshan; Langenbach, Robert; Li, Hong; Zeldin, Darryl; Chen, Shiou-Lan; Wang, Shijun; Gao, Huiming; Lu, Ru-Band; Hong, Jau-Shyong

    2015-08-01

    Regulatory mechanisms of the expression of interleukin-10 (IL-10) in brain inflammatory conditions remain elusive. To address this issue, we used multiple primary brain cell cultures to study the expression of IL-10 in lipopolysaccharide (LPS)-elicited inflammatory conditions. In neuron-glia cultures, LPS triggered well-orchestrated expression of various immune factors in the following order: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and lastly IL-10, and these inflammatory mediators were mainly produced from microglia. While exogenous application of individual earlier-released pro-inflammatory factors (e.g., TNF-α, IL-1β, or PGE2) failed to induce IL-10 expression, removal of LPS from the cultures showed the requirement of continuing presence of LPS for IL-10 expression. Interestingly, genetic disruption of tnf-α, its receptors tnf-r1/r2, and cox-2 and pharmacological inhibition of COX-2 activity enhanced LPS-induced IL-10 production in microglia, which suggests negative regulation of IL-10 induction by the earlier-released TNF-α and PGE2. Further studies showed that negative regulation of IL-10 production by TNF-α is mediated by PGE2. Mechanistic studies indicated that PGE2-elicited suppression of IL-10 induction was eliminated by genetic disruption of the PGE2 receptor EP2 and was mimicked by the specific agonist for the EP2, butaprost, but not agonists for the other three EP receptors. Inhibition of cAMP-dependent signal transduction failed to affect PGE2-mediated inhibition of IL-10 production, suggesting that a G protein-independent pathway was involved. Indeed, deficiency in β-arrestin-1 or β-arrestin-2 abolished PGE2-elicited suppression of IL-10 production. In conclusion, we have demonstrated that COX-2-derived PGE2 inhibits IL-10 expression in brain microglia through a novel EP2- and β-arrestin-dependent signaling pathway.

  10. Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis

    PubMed Central

    Cahill, Thomas J.; Thomsen, Alex R. B.; Tarrasch, Jeffrey T.; Plouffe, Bianca; Nguyen, Anthony H.; Yang, Fan; Huang, Li-Yin; Kahsai, Alem W.; Bassoni, Daniel L.; Gavino, Bryant J.; Lamerdin, Jane E.; Triest, Sarah; Shukla, Arun K.; Berger, Benjamin; Little, John; Antar, Albert; Blanc, Adi; Qu, Chang-Xiu; Chen, Xin; Kawakami, Kouki; Inoue, Asuka; Aoki, Junken; Steyaert, Jan; Sun, Jin-Peng; Bouvier, Michel; Skiniotis, Georgios; Lefkowitz, Robert J.

    2017-01-01

    β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR–βarr complexes: the “tail” conformation, with βarr primarily coupled to the phosphorylated GPCR C-terminal tail, and the “core” conformation, where, in addition to the phosphorylated C-terminal tail, βarr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of βarrs is unknown. Here, we created a mutant form of βarr lacking the “finger-loop” region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and βarr signaling but not desensitization of G protein signaling. Thus, the two GPCR–βarr conformations can carry out distinct functions. PMID:28223524

  11. Role of receptor-attached phosphates in binding of visual and non-visual arrestins to G protein-coupled receptors.

    PubMed

    Gimenez, Luis E; Kook, Seunghyi; Vishnivetskiy, Sergey A; Ahmed, M Rafiuddin; Gurevich, Eugenia V; Gurevich, Vsevolod V

    2012-03-16

    Arrestins are a small family of proteins that regulate G protein-coupled receptors (GPCRs). Arrestins specifically bind to phosphorylated active receptors, terminating G protein coupling, targeting receptors to endocytic vesicles, and initiating G protein-independent signaling. The interaction of rhodopsin-attached phosphates with Lys-14 and Lys-15 in β-strand I was shown to disrupt the interaction of α-helix I, β-strand I, and the C-tail of visual arrestin-1, facilitating its transition into an active receptor-binding state. Here we tested the role of conserved lysines in homologous positions of non-visual arrestins by generating K2A mutants in which both lysines were replaced with alanines. K2A mutations in arrestin-1, -2, and -3 significantly reduced their binding to active phosphorhodopsin in vitro. The interaction of arrestins with several GPCRs in intact cells was monitored by a bioluminescence resonance energy transfer (BRET)-based assay. BRET data confirmed the role of Lys-14 and Lys-15 in arrestin-1 binding to non-cognate receptors. However, this was not the case for non-visual arrestins in which the K2A mutations had little effect on net BRET(max) values for the M2 muscarinic acetylcholine (M2R), β(2)-adrenergic (β(2)AR), or D2 dopamine receptors. Moreover, a phosphorylation-deficient mutant of M2R interacted with wild type non-visual arrestins normally, whereas phosphorylation-deficient β(2)AR mutants bound arrestins at 20-50% of the level of wild type β(2)AR. Thus, the contribution of receptor-attached phosphates to arrestin binding varies depending on the receptor-arrestin pair. Although arrestin-1 always depends on receptor phosphorylation, its role in the recruitment of arrestin-2 and -3 is much greater in the case of β(2)AR than M2R and D2 dopamine receptor.

  12. Dopamine D2 receptor and β-arrestin 2 mediate Amyloid-β elevation induced by anti-parkinson’s disease drugs, levodopa and piribedil, in neuronal cells

    PubMed Central

    Wang, Qinying; Pei, Gang

    2017-01-01

    Although levodopa is the first-line medication for the treatment of Parkinson’s disease (PD) showing unsurpassable efficiency, its chronic use causes dyskinesia. Accordingly, dopamine agonists are increasingly employed as monotherapy or in combination with levodopa to reduce the risk of motor complications. It is well recognized that patients with PD often exhibit cognitive deficits. However, clinical and animal studies assessing the effects of dopaminergic medications on cognition are controversial. Amyloid-β (Aβ) is one of the major hallmarks of Alzheimer’s disease (AD), leading to progressive memory loss and cognitive deficit. Interestingly, the abnormal accumulation of Aβ is also detected in PD patients with cognitive deficits. Evidence indicated that levodopa induced a mild increase of Aβ plaque number and size in the brain of AD mouse. However, the underlying mechanism is unclear. Here we present that both levodopa and piribedil enhance the generation of Aβ and the activity of γ-secretase in human neuronal cells and primary neurons isolated from AD mouse. This effect was reduced by either the antagonism or the knockdown of dopamine D2 receptor (D2R). We further showed that in the cells expressing β-arrestin 2-biased D2R mutant, piribedil promoted cellular Aβ production to the extent comparable to the wild-type D2R whereas this activity was absent in those with G protein-biased D2R mutant. Moreover, the knockdown of β-arrestin 2 attenuated the increases of Aβ generation and γ-secretase activity mediated by levodopa or piribedil. Thus, our study suggests that targeting D2R-mediated β-arrestin function may have potential risk in the modulation of Aβ pathology. PMID:28253352

  13. Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response in Saccharomyces cerevisiae

    PubMed Central

    Alvaro, Christopher G.; Aindow, Ann; Thorner, Jeremy

    2016-01-01

    G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate stimulus-dependent activation of cognate heterotrimeric G-proteins, triggering ensuing downstream cellular responses. Tight regulation of GPCR-evoked pathways is required because prolonged stimulation can be detrimental to an organism. Ste2, a GPCR in Saccharomyces cerevisiae that mediates response of MATa haploids to the peptide mating pheromone α-factor, is down-regulated by both constitutive and agonist-induced endocytosis. Efficient agonist-stimulated internalization of Ste2 requires its association with an adaptor protein, the α-arrestin Rod1/Art4, which recruits the HECT-domain ubiquitin ligase Rsp5, allowing for ubiquitinylation of the C-terminal tail of the receptor and its engagement by the clathrin-dependent endocytic machinery. We previously showed that dephosphorylation of Rod1 by calcineurin (phosphoprotein phosphatase 2B) is required for optimal Rod1 function in Ste2 down-regulation. We show here that negative regulation of Rod1 by phosphorylation is mediated by two distinct stress-activated protein kinases, Snf1/AMPK and Ypk1/SGK1, and demonstrate both in vitro and in vivo that this phospho-regulation impedes the ability of Rod1 to promote mating pathway desensitization. These studies also revealed that, in the absence of its phosphorylation, Rod1 can promote adaptation independently of Rsp5-mediated receptor ubiquitinylation, consistent with recent evidence that α-arrestins can contribute to cargo recognition by both clathrin-dependent and clathrin-independent mechanisms. However, in cells lacking a component (formin Bni1) required for clathrin-independent entry, Rod1 derivatives that are largely unphosphorylated and unable to associate with Rsp5 still promote efficient adaptation, indicating a third mechanism by which this α-arrestin promotes desensitization of the pheromone-response pathway. PMID:26920760

  14. Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response in Saccharomyces cerevisiae.

    PubMed

    Alvaro, Christopher G; Aindow, Ann; Thorner, Jeremy

    2016-05-01

    G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate stimulus-dependent activation of cognate heterotrimeric G-proteins, triggering ensuing downstream cellular responses. Tight regulation of GPCR-evoked pathways is required because prolonged stimulation can be detrimental to an organism. Ste2, a GPCR in Saccharomyces cerevisiae that mediates response of MATa haploids to the peptide mating pheromone α-factor, is down-regulated by both constitutive and agonist-induced endocytosis. Efficient agonist-stimulated internalization of Ste2 requires its association with an adaptor protein, the α-arrestin Rod1/Art4, which recruits the HECT-domain ubiquitin ligase Rsp5, allowing for ubiquitinylation of the C-terminal tail of the receptor and its engagement by the clathrin-dependent endocytic machinery. We previously showed that dephosphorylation of Rod1 by calcineurin (phosphoprotein phosphatase 2B) is required for optimal Rod1 function in Ste2 down-regulation. We show here that negative regulation of Rod1 by phosphorylation is mediated by two distinct stress-activated protein kinases, Snf1/AMPK and Ypk1/SGK1, and demonstrate both in vitro and in vivo that this phospho-regulation impedes the ability of Rod1 to promote mating pathway desensitization. These studies also revealed that, in the absence of its phosphorylation, Rod1 can promote adaptation independently of Rsp5-mediated receptor ubiquitinylation, consistent with recent evidence that α-arrestins can contribute to cargo recognition by both clathrin-dependent and clathrin-independent mechanisms. However, in cells lacking a component (formin Bni1) required for clathrin-independent entry, Rod1 derivatives that are largely unphosphorylated and unable to associate with Rsp5 still promote efficient adaptation, indicating a third mechanism by which this α-arrestin promotes desensitization of the pheromone-response pathway.

  15. Differential requirements of arrestin-3 and clathrin for ligand-dependent and -independent internalization of human G protein-coupled receptor 40.

    PubMed

    Qian, Jing; Wu, Chun; Chen, Xiaopan; Li, Xiangmei; Ying, Guoyuan; Jin, Lili; Ma, Qiang; Li, Guo; Shi, Ying; Zhang, Guozheng; Zhou, Naiming

    2014-11-01

    G protein-coupled receptor 40 (GPR40) is believed to be an attractive target to enhance insulin secretion in patients with type 2 diabetes. GPR40 has been found to couple to Gq protein, leading to the activation of phospholipase C and subsequent increases in the intracellular Ca(2+) level. However, the underlying mechanisms that regulate the internalization and desensitization of GPR40 remain to be elucidated. In the present study, a construct of GPR40 fused with enhanced green fluorescent protein (EGFP) at its C-terminus was constructed for direct imaging of the localization and internalization of GPR40 by confocal microscopy. In stably transfected HEK-293 cells, GPR40 receptors underwent rapid agonist-induced internalization and constitutive ligand-independent internalization. Our data demonstrated that the agonist-mediated internalization of GPR40 was significantly blocked by hypertonic sucrose treatment and by siRNA mediated depletion of the heavy chain of clathrin. In contrast, constitutive GPR40 internalization was not affected by hypertonic sucrose or by knock-down of clathrin expression, but it was affected by treatment with methyl-β-cyclodextrin (MβCD) and nystatin. Furthermore, our results using an arrestin-3-EGFP redistribution assay and siRNA-mediated knock-down of arrestin-3 and GRK2 expression revealed that arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. Additionally, our observation showed that upon activation by agonist, the internalized GPR40 receptors were rapidly recycled back to the plasma membrane via Rab4/Rab5 positive endosomes, whereas the constitutively internalized GPR40 receptors were recycled back to the cell surface through Rab5 positive endosomes. Because FFA receptors exhibit a high level of homology, our observations could be applicable to other members of this family.

  16. The prostaglandin receptor EP2 activates multiple signaling pathways and beta-arrestin1 complex formation during mouse skin papilloma development.

    PubMed

    Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S; Okada, Manabu; Langenbach, Robert

    2009-09-01

    Prostaglandin E(2) (PGE(2)) is elevated in many tumor types, but PGE(2)'s contributions to tumor growth are largely unknown. To investigate PGE(2)'s roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors-cyclic adenosine 3',5'-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2-were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE(2) production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3',5'-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2-/- mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR-beta-arrestin-Src complex. Indeed, immunoprecipitation of beta-arrestin1 or p-Src indicated the presence of an EP2-beta-arrestin1-p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with beta-arrestin1 and Src that contributed to signaling and/or EP2 desensitization.

  17. Multiplexed assays by high-content imaging for assessment of GPCR activity.

    PubMed

    Ross, D A; Lee, S; Reiser, V; Xue, J; Alves, K; Vaidya, S; Kreamer, A; Mull, R; Hudak, E; Hare, T; Detmers, P A; Lingham, R; Ferrer, M; Strulovici, B; Santini, F

    2008-07-01

    G-protein-coupled receptors (GPCR) participate in many disease pathways and represent the largest family of therapeutic targets. Thus, great investments are made to discover drugs modulating GPCR-mediated events. Among functional assays for screening GPCRs, the Transfluor imaging assay is based on redistribution of cytosolic beta-arrestin to an activated GPCR and has become widely used in high-content screening. However, assessing Transfluor alone has limitations: relying on a single mechanistic step of beta-arrestin redistribution during GPCR activation, providing no information on the stimulated GPCR's intracellular fate, and using only a single fluorescent color (green fluorescent protein). Taking full advantage of high-content imaging to screen approximately 2000 compounds, the authors multiplexed the Transfluor assay with an immunofluorescence-based quantification of GPCR internalization. This approach identified and classified 377 compounds interfering with agonist-induced activation of the Transfluor assay, receptor internalization, or both. In addition, a subset of compounds was analyzed for their performance across imaging, cell-based calcium release (fluorometric imaging plate reader [FLIPR]), and biochemical receptor binding assays (scintillation proximity assay). This indicated that the imaging assays have even better predictive power for direct inhibition of receptor binding than the FLIPR assay. In conclusion, compounds inducing unique responses can suggest novel mechanisms of action and be used as tools to study GPCR activation and internalization.

  18. The carboxy-terminal tail or the intracellular loop 3 is required for β-arrestin-dependent internalization of a mammalian type II GnRH receptor.

    PubMed

    Madziva, Michael T; Mkhize, Nonhlanhla N; Flanagan, Colleen A; Katz, Arieh A

    2015-08-15

    The type II GnRH receptor (GnRH-R2) in contrast to mammalian type I GnRH receptor (GnRH-R1) has a cytosolic carboxy-terminal tail. We investigated the role of β-arrestin 1 in GnRH-R2-mediated signalling and mapped the regions in GnRH-R2 required for recruitment of β-arrestin, employing internalization assays. We show that GnRH-R2 activation of ERK is dependent on β-arrestin and protein kinase C. Appending the tail of GnRH-R2 to GnRH-R1 enabled GRK- and β-arrestin-dependent internalization of the chimaeric receptor. Surprisingly, carboxy-terminally truncated GnRH-R2 retained β-arrestin and GRK-dependent internalization, suggesting that β-arrestin interacts with additional elements of GnRH-R2. Mutating serine and threonine or basic residues of intracellular loop 3 did not abolish β-arrestin 1-dependent internalization but a receptor lacking these basic residues and the carboxy-terminus showed no β-arrestin 1-dependent internalization. Our results suggest that basic residues at the amino-terminal end of intracellular loop 3 or the carboxy-terminal tail are required for β-arrestin dependent internalization.

  19. The induction of thioredoxin-1 by epinephrine withdraws stress via interaction with β-arrestin-1.

    PubMed

    Jia, Jin-Jing; Zeng, Xian-Si; Zhou, Xiao-Shuang; Li, Ye; Bai, Jie

    2014-01-01

    Stress regulates a panel of important physiological functions and disease states. Epinephrine is produced under stresses threaten to homeostasis. Thioredoxin-1(Trx-1) is a redox regulating protein which is induced to resist stresses and related with various diseases. Thus, it is important to examine whether Trx-1 is induced by epinephrine and to understand the underlying molecular mechanisms that Trx-1 modulates epinephrine stress. Here, we show that the expression of Trx-1 was induced by epinephrine via β-adrenergic receptor/Cyclic AMP/protein kinase A (PKA) signaling pathway in PC12 cells. The down-regulation of Trx-1 by siRNA aggravated accumulation of γ-H2AX and further decreased expression of p53 by epinephrine. Accordingly, Trx-1 overexpression alleviated accumulation of γ-H2AX and restored the expressions of p53 and C/EBP homologous protein (CHOP) in the cortex, hippocampus and thymus of mice. Moreover, Trx-1 overexpression reduced the malondialdehyde concentration by epinephrine. We further explored the mechanism on p53 and γ-H2AX regulated by Trx-1. We found that overexpression of Trx-1 suppressed β-arrestin-1 expression through interaction with β-arrestin-1. Consequently, the downregulation of β-arrestin-1 suppressed the cell viability and the expressions of γ-H2AX and cyclin D1, and increased p53 expression. Taken together, our data suggest that Trx-1/β-arrestin-1 interaction may represent a novel endogenous mechanism on protecting against stress.

  20. The Role of CXCR4 and Arrestins in Breast Cancer Signaling and Apoptosis

    DTIC Science & Technology

    2006-02-01

    in GPCR trafficking and signaling both at the cell surface and post- endocytically . Therefore, understanding GPCR function in the absence of arrestins...FPR- mediated apoptosis. Also, these mutants show trafficking defects and may be related to AP-2, a regulator of cellular trafficking. In this report...expressing cell . Only expression of arr2-WT rescues FPR- mediated apoptosis whereas EGFP vector and arr2-PP do not. While this mutant has been

  1. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex

    DOE PAGES

    Zhou, X. Edward; Gao, Xiang; Barty, Anton; ...

    2016-04-12

    Here, serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solvedmore » with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes.« less

  2. Mutations in arrestin-3 differentially affect binding to neuropeptide Y receptor subtypes.

    PubMed

    Gimenez, Luis E; Babilon, Stefanie; Wanka, Lizzy; Beck-Sickinger, Annette G; Gurevich, Vsevolod V

    2014-07-01

    Based on the identification of residues that determine receptor selectivity in arrestins and the phylogenetic analysis of the arrestin (arr) family, we introduced fifteen mutations of receptor-discriminator residues in arr-3, which were identified previously using mutagenesis, in vitro binding, and BRET-based recruitment assay in intact cells. The effects of these mutations were tested using neuropeptide Y receptors Y1R and Y2R. NPY-elicited arr-3 recruitment to Y1R was not affected by these mutations, or even alanine substitution of all ten residues (arr-3-NCA), which prevented arr-3 binding to other receptors tested so far. However, NCA and two other mutations prevented agonist-independent arr-3 pre-docking to Y1R. In contrast, eight out of 15 mutations significantly reduced agonist-dependent arr-3 recruitment to Y2R. NCA eliminated arr-3 binding to active Y2R, whereas Tyr239Thr reduced it ~7-fold. Thus, manipulation of key residues on the receptor-binding surface generates arr-3 with high preference for Y1R over Y2R. Several mutations differentially affect arr-3 pre-docking and agonist-induced recruitment. Thus, arr-3 recruitment to the receptor involves several mechanistically distinct steps. Targeted mutagenesis can fine-tune arrestins directing them to specific receptors and particular activation states of the same receptor.

  3. Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell development in Magnaporthe oryzae

    PubMed Central

    Dong, Bo; Xu, Xiaojin; Chen, Guoqing; Zhang, Dandan; Tang, Mingzhi; Xu, Fei; Liu, Xiaohong; Wang, Hua; Zhou, Bo

    2016-01-01

    Conidiation patterning is evolutionarily complex and mechanism concerning conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae conidiates in a sympodial way and uses its conidia to infect host and disseminate blast disease. Arrestins are multifunctional proteins that modulate receptor down-regulation and scaffold components of intracellular trafficking routes. We here report an alpha-arrestin that regulates patterns of conidiation and contributes to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates mutants which produce conidia in an acropetal array and ARRDC1 significantly affects expression profile of CCA1, a virulence-related transcription factor required for conidiogenous cell differentiation. Although germ tubes normally develop appressoria, penetration peg formation is dramatically impaired and Δarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution profile could not be altered in Δatg9 mutants, suggesting ARRDC1 enters into autophagic flux before autophagosome maturation. We propose that M. oryzae employs ARRDC1 to regulate specific receptors in response to conidiation-related signals for conidiogenous cell differentiation and utilize autophagosomes for desensitization of conidiogenous receptor, which transmits extracellular signal to the downstream elements of transcription factors. Our investigation extends novel significance of autophagy-associated alpha-arrestin signaling to fungal parasites. PMID:27498554

  4. Mutations in arrestin-3 differentially affect binding to neuropeptide Y receptor subtypes

    PubMed Central

    Gimenez, Luis E.; Babilon, Stefanie; Wanka, Lizzy; Beck-Sickinger, Annette G.; Gurevich, Vsevolod V.

    2014-01-01

    Based on the identification of residues that determine receptor selectivity in arrestins and the phylogenetic analysis of the arrestin (arr) family, we introduced fifteen mutations of receptor-discriminator residues in arr-3, which were identified previously using mutagenesis, in vitro binding, and BRET-based recruitment assay in intact cells. The effects of these mutations were tested using neuropeptide Y receptors Y1R and Y2R. NPY-elicited arr-3 recruitment to Y1R was not affected by these mutations, or even alanine substitution of all ten residues (arr-3-NCA), which prevented arr-3 binding to other receptors tested so far. However, NCA and two other mutations prevented agonist-independent arr-3 pre-docking to Y1R. In contrast, eight out of 15 mutations significantly reduced agonist-dependent arr-3 recruitment to Y2R. NCA eliminated arr-3 binding to active Y2R, whereas Tyr239Thr reduced it ~7-fold. Thus, manipulation of key residues on the receptor-binding surface generates arr-3 with high preference for Y1R over Y2R. Several mutations differentially affect arr-3 pre-docking and agonist-induced recruitment. Thus, arr-3 recruitment to the receptor involves several mechanistically distinct steps. Targeted mutagenesis can fine-tune arrestins directing them to specific receptors and particular activation states of the same receptor. PMID:24686081

  5. Angiotensin II increases glomerular permeability by β-arrestin mediated nephrin endocytosis

    PubMed Central

    Königshausen, Eva; Zierhut, Ulf M.; Ruetze, Martin; Potthoff, Sebastian A.; Stegbauer, Johannes; Woznowski, Magdalena; Quack, Ivo; Rump, Lars C.; Sellin, Lorenz

    2016-01-01

    Glomerular permeability and subsequent albuminuria are early clinical markers for glomerular injury in hypertensive nephropathy. Albuminuria predicts mortality and cardiovascular morbidity. AT1 receptor blockers protect from albuminuria, cardiovascular morbidity and mortality. A blood pressure independent, molecular mechanism for angiotensin II (Ang II) dependent albuminuria has long been postulated. Albuminuria results from a defective glomerular filter. Nephrin is a major structural component of the glomerular slit diaphragm and its endocytosis is mediated by β-arrestin2. Ang II stimulation increases nephrin-β-arrestin2 binding, nephrin endocytosis and glomerular permeability in mice. This Ang II effect is mediated by AT1-receptors. AT1-receptor mutants identified G-protein signaling to be essential for this Ang II effect. Gαq knockdown and phospholipase C inhibition block Ang II mediated enhanced nephrin endocytosis. Nephrin Y1217 is the critical residue controlling nephrin binding to β-arrestin under Ang II stimulation. Nephrin Y1217 also mediates cytoskeletal anchoring to actin via nck2. Ang II stimulation decreases nephrin nck2 binding. We conclude that Ang II weakens the structural integrity of the slit diaphragm by increased nephrin endocytosis and decreased nephrin binding to nck2, which leads to increased glomerular permeability. This novel molecular mechanism of Ang II supports the use of AT1-receptor blockers to prevent albuminuria even in normotensives. PMID:28004760

  6. Not just signal shutoff: the protective role of arrestin-1 in rod cells.

    PubMed

    Sommer, Martha E; Hofmann, Klaus Peter; Heck, Martin

    2014-01-01

    The retinal rod cell is an exquisitely sensitive single-photon detector that primarily functions in dim light (e.g., moonlight). However, rod cells must routinely survive light intensities more than a billion times greater (e.g., bright daylight). One serious challenge to rod cell survival in daylight is the massive amount of all-trans-retinal that is released by Meta II, the light-activated form of the photoreceptor rhodopsin. All-trans-retinal is toxic, and its condensation products have been implicated in disease. Our recent work has developed the concept that rod arrestin (arrestin-1), which terminates Meta II signaling, has an additional role in protecting rod cells from the consequences of bright light by limiting free all-trans-retinal. In this chapter we will elaborate upon the molecular mechanisms by which arrestin-1 serves as both a single-photon response quencher as well as an instrument of rod cell survival in bright light. This discussion will take place within the framework of three distinct functional modules of vision: signal transduction, the retinoid cycle, and protein translocation.

  7. Neurotensin-induced Proinflammatory Signaling in Human Colonocytes Is Regulated by β-Arrestins and Endothelin-converting Enzyme-1-dependent Endocytosis and Resensitization of Neurotensin Receptor 1*

    PubMed Central

    Law, Ivy Ka Man; Murphy, Jane E.; Bakirtzi, Kyriaki; Bunnett, Nigel W.; Pothoulakis, Charalabos

    2012-01-01

    The neuropeptide/hormone neurotensin (NT) mediates intestinal inflammation and cell proliferation by binding of its high affinity receptor, neurotensin receptor-1 (NTR1). NT stimulates IL-8 expression in NCM460 human colonic epithelial cells by both MAP kinase- and NF-κB-dependent pathways. Although the mechanism of NTR1 endocytosis has been studied, the relationship between NTR1 intracellular trafficking and inflammatory signaling remains to be elucidated. In the present study, we show that in NCM460 cells exposed to NT, β-arrestin-1 (βARR1), and β-arrestin-2 (βARR2) translocate to early endosomes together with NTR1. Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its activity is crucial for NTR1 recycling. Pretreatment of NCM460 cells with the ECE-1 inhibitor SM19712 or gene silencing of βARR1 or βARR2 inhibits NT-stimulated ERK1/2 and JNK phosphorylation, NF-κB p65 nuclear translocation and phosphorylation, and IL-8 secretion. Furthermore, NT-induced cell proliferation, but not IL-8 transcription, is attenuated by the JNK inhibitor, JNK(AII). Thus, NTR1 internalization and recycling in human colonic epithelial cells involves βARRs and ECE-1, respectively. Our results also indicate that βARRs and ECE-1-dependent recycling regulate MAP kinase and NF-κB signaling as well as cell proliferation in human colonocytes in response to NT. PMID:22416137

  8. Differences in the C-terminus contribute to variations in trafficking between rat and human 5-HT(2A) receptor isoforms: identification of a primate-specific tripeptide ASK motif that confers GRK-2 and beta arrestin-2 interactions.

    PubMed

    Bhattacharya, Aditi; Sankar, Shobhana; Panicker, Mitradas M

    2010-02-01

    Internalization and recycling of G-protein coupled receptors are important cellular processes regulating receptor function. These are receptor-subtype and cell type-specific. Although important, trafficking variations between receptor isoforms of different species has received limited attention. We report here, differences in internalization and recycling between rat and human serotonin 2A receptor (5-HT(2A)R) isoforms expressed in human embryonic kidney 293 cells in response to serotonin. Although the human and rat 5-HT(2A)Rs differ by only a few amino acids, the human receptor takes longer to recycle to the cell surface after internalization, with the additional involvement of beta arrestin-2 and G-protein receptor kinase 2. The interaction of beta arrestin-2 with the human receptor causes the delay in recycling and is dependent on a primate-specific ASK motif present in the C-terminus of the receptor. Conversion of this motif to NCT, the corresponding sequence present in the rat isoform, results in the human isoform trafficking like the rat receptor. Replacing the serine 457 with alanine in the ASK motif of human isoform resulted in faster recycling, although with continued arrestin-dependent internalization. This study establishes significant differences between the two isoforms with important implications in our understanding of the human 5-HT(2A)R functions; and indicates that extrapolating results from non-human receptor isoforms to human subtypes is not without caveats.

  9. Maryland State Content Standards: Social Studies.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Education, Baltimore.

    Social studies should be viewed as a major subject matter area in kindergarten through eighth grade, and in specific courses in high school. Students should develop the knowledge and skills to understand and cope with change, resolve conflict, analyze issues, and appreciate diversity in a representative democracy. By the time Maryland students…

  10. A Study in Content Area Language Acquisition

    ERIC Educational Resources Information Center

    Broer, Kathleen

    2003-01-01

    This study was conducted at a public school with a population of over 900 students. Among the main language groups represented were Punjabi, Hindi, Tamil, Estonian, Serbian, Arabic as well as 23 other language groups. The author monitored over 75 students, in grades 1, 2 and 4. She was interested in exploring what strategies best promoted…

  11. A Study in Content Language Acquisition

    ERIC Educational Resources Information Center

    Broer, Kathleen

    2003-01-01

    This study examines how young second language learners acquire academic language. Among the main language groups represented were Punjabi, Hindi, Tamil, Estonian, Serbian, Arabic as well as 23 other language groups. I monitored over 75 students, in grades 1, 2 and 4. I was interested in exploring what strategies best promoted coherence in…

  12. Internal Amino Acids Promote Gap1 Permease Ubiquitylation via TORC1/Npr1/14-3-3-Dependent Control of the Bul Arrestin-Like Adaptors

    PubMed Central

    Merhi, Ahmad

    2012-01-01

    Ubiquitylation of many plasma membrane proteins promotes their endocytosis followed by degradation in the lysosome. The yeast general amino acid permease, Gap1, is ubiquitylated and downregulated when a good nitrogen source like ammonium is provided to cells growing on a poor nitrogen source. This ubiquitylation requires the Rsp5 ubiquitin ligase and the redundant arrestin-like Bul1 and Bul2 adaptors. Previous studies have shown that Gap1 ubiquitylation involves the TORC1 kinase complex, which inhibits the Sit4 phosphatase. This causes inactivation of the protein kinase Npr1, which protects Gap1 against ubiquitylation. However, the mechanisms inducing Gap1 ubiquitylation after Npr1 inactivation remain unknown. We here show that on a poor nitrogen source, the Bul adaptors are phosphorylated in an Npr1-dependent manner and bound to 14-3-3 proteins that protect Gap1 against downregulation. After ammonium is added and converted to amino acids, the Bul proteins are dephosphorylated, dissociate from the 14-3-3 proteins, and undergo ubiquitylation. Furthermore, dephosphorylation of Bul requires the Sit4 phosphatase, which is essential to Gap1 downregulation. The data support the emerging concept that permease ubiquitylation results from activation of the arrestin-like adaptors of the Rsp5 ubiquitin ligase, this coinciding with their dephosphorylation, dissociation from the inhibitory 14-3-3 proteins, and ubiquitylation. PMID:22966204

  13. G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transfer.

    PubMed

    Violin, Jonathan D; Ren, Xiu-Rong; Lefkowitz, Robert J

    2006-07-21

    The small family of G-protein-coupled receptor kinases (GRKs) regulate cell signaling by phosphorylating heptahelical receptors, thereby promoting receptor interaction with beta-arrestins. This switches a receptor from G-protein activation to G-protein desensitization, receptor internalization, and beta-arrestin-dependent signal activation. However, the specificity of GRKs for recruiting beta-arrestins to specific receptors has not been elucidated. Here we use the beta(2)-adrenergic receptor (beta(2)AR), the archetypal nonvisual heptahelical receptor, as a model to test functional GRK specificity. We monitor endogenous GRK activity with a fluorescence resonance energy transfer assay in live cells by measuring kinetics of the interaction between the beta(2)AR and beta-arrestins. We show that beta(2)AR phosphorylation is required for high affinity beta-arrestin binding, and we use small interfering RNA silencing to show that HEK-293 and U2-OS cells use different subsets of their expressed GRKs to promote beta-arrestin recruitment, with significant GRK redundancy evident in both cell types. Surprisingly, the GRK specificity for beta-arrestin recruitment does not correlate with that for bulk receptor phosphorylation, indicating that beta-arrestin recruitment is specific for a subset of receptor phosphorylations on specific sites. Moreover, multiple members of the GRK family are able to phosphorylate the beta(2)AR and induce beta-arrestin recruitment, with their relative contributions largely determined by their relative expression levels. Because GRK isoforms vary in their regulation, this partially redundant system ensures beta-arrestin recruitment while providing the opportunity for tissue-specific regulation of the rate of beta-arrestin recruitment.

  14. Selectively engaging β-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance.

    PubMed

    Violin, Jonathan D; DeWire, Scott M; Yamashita, Dennis; Rominger, David H; Nguyen, Lisa; Schiller, Kevin; Whalen, Erin J; Gowen, Maxine; Lark, Michael W

    2010-12-01

    Biased G protein-coupled receptor ligands engage subsets of the receptor signals normally stimulated by unbiased agonists. However, it is unclear whether ligand bias can elicit differentiated pharmacology in vivo. Here, we describe the discovery of a potent, selective β-arrestin biased ligand of the angiotensin II type 1 receptor. TRV120027 (Sar-Arg-Val-Tyr-Ile-His-Pro-D-Ala-OH) competitively antagonizes angiotensin II-stimulated G protein signaling, but stimulates β-arrestin recruitment and activates several kinase pathways, including p42/44 mitogen-activated protein kinase, Src, and endothelial nitric-oxide synthase phosphorylation via β-arrestin coupling. Consistent with β-arrestin efficacy, and unlike unbiased antagonists, TRV120027 increased cardiomyocyte contractility in vitro. In rats, TRV120027 reduced mean arterial pressure, as did the unbiased antagonists losartan and telmisartan. However, unlike the unbiased antagonists, which decreased cardiac performance, TRV120027 increased cardiac performance and preserved cardiac stroke volume. These striking differences in vivo between unbiased and β-arrestin biased ligands validate the use of biased ligands to selectively target specific receptor functions in drug discovery.

  15. Direct visualisation of internalization of the adenosine A3 receptor and localization with arrestin3 using a fluorescent agonist.

    PubMed

    Stoddart, Leigh A; Vernall, Andrea J; Briddon, Stephen J; Kellam, Barrie; Hill, Stephen J

    2015-11-01

    Fluorescence based probes provide a novel way to study the dynamic internalization process of G protein-coupled receptors (GPCRs). Recent advances in the rational design of fluorescent ligands for GPCRs have been used here to generate new fluorescent agonists containing tripeptide linkers for the adenosine A3 receptor. The fluorescent agonist BY630-X-(D)-A-(D)-A-G-ABEA was found to be a highly potent agonist at the adenosine A3 receptor in both reporter gene (pEC50 = 8.48 ± 0.09) and internalization assays (pEC50 = 7.47 ± 0.11). Confocal imaging studies showed that BY630-X-(D)-A-(D)-A-G-ABEA was internalized with A3 linked to yellow fluorescent protein, which was blocked by the competitive antagonist MRS1220. Internalization of untagged adenosine A3 could also be visualized with BY630-X-(D)-A-(D)-A-G-ABEA treatment. Further, BY630-X-(D)-A-(D)-A-G-ABEA stimulated the formation of receptor-arrestin3 complexes and was found to localize with these intracellular complexes. This highly potent agonist with excellent imaging properties should be a valuable tool to study receptor internalization. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'.

  16. Mathematical Modelling Research in Turkey: A Content Analysis Study

    ERIC Educational Resources Information Center

    Çelik, H. Coskun

    2017-01-01

    The aim of the present study was to examine the mathematical modelling studies done between 2004 and 2015 in Turkey and to reveal their tendencies. Forty-nine studies were selected using purposeful sampling based on the term, "mathematical modelling" with Higher Education Academic Search Engine. They were analyzed with content analysis.…

  17. Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice.

    PubMed

    Park, Su M; Chen, Meng; Schmerberg, Claire M; Dulman, Russell S; Rodriguiz, Ramona M; Caron, Marc G; Jin, Jian; Wetsel, William C

    2016-02-01

    Current antipsychotic drugs (APDs) show efficacy with positive symptoms, but are limited in treating negative or cognitive features of schizophrenia. Whereas all currently FDA-approved medications target primarily the dopamine D2 receptor (D2R) to inhibit G(i/o)-mediated adenylyl cyclase, a recent study has shown that many APDs affect not only G(i/o)- but they can also influence β-arrestin- (βArr)-mediated signaling. The ability of ligands to differentially affect signaling through these pathways is termed functional selectivity. We have developed ligands that are devoid of D2R-mediated G(i/o) protein signaling, but are simultaneously partial agonists for D2R/βArr interactions. The purpose of this study was to test the effectiveness of UNC9975 or UNC9994 on schizophrenia-like behaviors in phencyclidine-treated or NR1-knockdown hypoglutamatergic mice. We have found the UNC compounds reduce hyperlocomotion in the open field, restore PPI, improve novel object recognition memory, partially normalize social behavior, decrease conditioned avoidance responding, and elicit a much lower level of catalepsy than haloperidol. These preclinical results suggest that exploitation of functional selectivity may provide unique opportunities to develop drugs with fewer side effects, greater therapeutic selectivity, and enhanced efficacy for treating schizophrenia and related conditions than medications that are currently available.

  18. Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery.

    PubMed

    Bohn, Laura M; McDonald, Patricia H

    2010-01-01

    G protein-coupled receptors (GPCR) are the major site of action for endogenous hormones and neurotransmitters. Early drug discovery efforts focused on determining whether ligands could engage G protein coupling and subsequently activate or inhibit cognate "second messengers." Gone are those simple days as we now realize that receptors can also couple βarrestins. As we delve into the complexity of ligand-directed signaling and receptosome scaffolds, we are faced with what may seem like endless possibilities triggered by receptor-ligand mediated events.

  19. The prostaglandin receptor EP2 activates multiple signaling pathways and β-arrestin1 complex formation during mouse skin papilloma development

    PubMed Central

    Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S.; Okada, Manabu; Langenbach, Robert

    2009-01-01

    Prostaglandin E2 (PGE2) is elevated in many tumor types, but PGE2's contributions to tumor growth are largely unknown. To investigate PGE2's roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors—cyclic adenosine 3′,5′-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2—were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE2 production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3′,5′-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2−/− mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR–β-arrestin–Src complex. Indeed, immunoprecipitation of β-arrestin1 or p-Src indicated the presence of an EP2–β-arrestin1–p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with β-arrestin1 and Src that contributed to signaling and/or EP2

  20. Pedagogical Content Knowledge: A Case Study of ESL Teacher Educator

    ERIC Educational Resources Information Center

    Liu, Siping

    2013-01-01

    This single-case study focuses on the pedagogical content knowledge (PCK) of a university faculty member teaching Second Language Acquisition to elementary teacher candidates. The research questions address the pattern and development of PCK for ESL teaching. Based on data from classroom observation, interviews and document review, the study finds…

  1. Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins

    PubMed Central

    Bouzo-Lorenzo, Monica; Santo-Zas, Icía; Lodeiro, Maria; Nogueiras, Rubén; Casanueva, Felipe F.; Castro, Marian; Pazos, Yolanda; Tobin, Andrew B; Butcher, Adrian J.; Camiña, Jesús P.

    2016-01-01

    The growth hormone secretagogue receptor, GHSR1a, mediates the biological activities of ghrelin, which includes the secretion of growth hormone, as well as the stimulation of appetite, food intake and maintenance of energy homeostasis. Mapping phosphorylation sites on GHSR1a and knowledge of how these sites control specific functional consequences unlocks new strategies for the development of therapeutic agents targeting individual functions. Herein, we have identified the phosphorylation of different sets of sites within GHSR1a which engender distinct functionality of ß-arrestins. More specifically, the Ser362, Ser363 and Thr366 residues at the carboxyl-terminal tail were primarily responsible for ß-arrestin 1 and 2 binding, internalization and ß-arrestin-mediated proliferation and adipogenesis. The Thr350 and Ser349 are not necessary for ß-arrestin recruitment, but are involved in the stabilization of the GHSR1a-ß-arrestin complex in a manner that determines the ultimate cellular consequences of ß-arrestin signaling. We further demonstrated that the mitogenic and adipogenic effect of ghrelin were mainly dependent on the ß-arrestin bound to the phosphorylated GHSR1a. In contrast, the ghrelin function on GH secretion was entirely mediated by G protein signaling. Our data is consistent with the hypothesis that the phosphorylation pattern on the C terminus of GHSR1a determines the signaling and physiological output. PMID:26935831

  2. Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors.

    PubMed

    Franklin, J M; Vasiljevik, T; Prisinzano, T E; Carrasco, G A

    2013-07-01

    Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT(2A)) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP55,940) or selective CB2 receptor agonists (JWH133 or GP1a) upregulate 5-HT(2A) receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT(2A) receptors was prevented in cells stably transfected with either CB2 or β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT(2A) receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT(2A) receptors by a mechanism that requires CB2 receptors and β-Arrestin 2 in cells that express both CB2 and 5-HT(2A) receptors. 5-HT(2A) receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.

  3. Tango assay for ligand-induced GPCR-β-arrestin2 interaction: Application in drug discovery.

    PubMed

    Dogra, Shalini; Sona, Chandan; Kumar, Ajeet; Yadav, Prem N

    2016-01-01

    G protein-coupled receptors (GPCRs) are widely known to modulate almost all physiological functions and have been demonstrated over the time as therapeutic targets for wide gamut of diseases. The design and implementation of high-throughput GPCR-based assays that permit the efficient screening of large compound libraries to discover novel drug candidates are essential for a successful drug discovery endeavor. Usually, GPCR-based functional assays depend primarily on the measurement of G protein-mediated second messenger generation. However, with advent of advanced molecular biology tools and increased understanding of GPCR signal transduction, many G protein-independent pathways such as β-arrestin translocation are being utilized to detect the activity of GPCRs. These assays provide additional information on functional selectivity (also known as biased agonism) of compounds that could be harnessed to develop pathway-selective drug candidates to reduce the adverse effects associated with given GPCR target. In this chapter, we describe the basic principle, detailed methodologies and assay setup, result analysis and data interpretations of the β-arrestin2 Tango assay, and its comparison with cell-based G protein-dependent GPCR assays, which could be employed in a simple academic setup to facilitate GPCR-based drug discovery.

  4. C-terminal motif of human neuropeptide Y4 receptor determines internalization and arrestin recruitment.

    PubMed

    Wanka, Lizzy; Babilon, Stefanie; Burkert, Kerstin; Mörl, Karin; Gurevich, Vsevolod V; Beck-Sickinger, Annette G

    2017-01-01

    The human neuropeptide Y4 receptor is a rhodopsin-like G protein-coupled receptor (GPCR), which contributes to anorexigenic signals. Thus, this receptor is a highly interesting target for metabolic diseases. As GPCR internalization and trafficking affect receptor signaling and vice versa, we aimed to investigate the molecular mechanism of hY4R desensitization and endocytosis. The role of distinct segments of the hY4R carboxyl terminus was investigated by fluorescence microscopy, binding assays, inositol turnover experiments and bioluminescence resonance energy transfer assays to examine the internalization behavior of hY4R and its interaction with arrestin-3. Based on results of C-terminal deletion mutants and substitution of single amino acids, the motif (7.78)EESEHLPLSTVHTEVSKGS(7.96) was identified, with glutamate, threonine and serine residues playing key roles, based on site-directed mutagenesis. Thus, we identified the internalization motif for the human neuropeptide Y4 receptor, which regulates arrestin-3 recruitment and receptor endocytosis.

  5. Regulation of Rho-GEF Rgf3 by the arrestin Art1 in fission yeast cytokinesis

    PubMed Central

    Davidson, Reshma; Laporte, Damien; Wu, Jian-Qiu

    2015-01-01

    Rho GTPases, activated by guanine nucleotide exchange factors (GEFs), are essential regulators of polarized cell growth, cytokinesis, and many other cellular processes. However, the regulation of Rho-GEFs themselves is not well understood. Rgf3 is an essential GEF for Rho1 GTPase in fission yeast. We show that Rgf3 protein levels and localization are regulated by arrestin-related protein Art1. art1∆ cells lyse during cell separation with a thinner and defective septum. As does Rgf3, Art1 concentrates to the contractile ring starting at early anaphase and spreads to the septum during and after ring constriction. Art1 localization depends on its C-terminus, and Art1 is important for maintaining Rgf3 protein levels. Biochemical experiments reveal that the Rgf3 C-terminus binds to Art1. Using an Rgf3 conditional mutant and mislocalization experiments, we found that Art1 and Rgf3 are interdependent for localization to the division site. As expected, active Rho1 levels at the division site are reduced in art1∆ and rgf3 mutant cells. Taken together, these data reveal that the arrestin family protein Art1 regulates the protein levels and localization of the Rho-GEF Rgf3, which in turn modulates active Rho1 levels during fission yeast cytokinesis. PMID:25473118

  6. β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.

    PubMed

    Raehal, Kirsten M; Bohn, Laura M

    2014-01-01

    Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of "pharmacological" interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects.

  7. β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia

    PubMed Central

    Bohn, Laura M.

    2016-01-01

    Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843

  8. Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling.

    PubMed

    Alvarez-Curto, Elisa; Inoue, Asuka; Jenkins, Laura; Raihan, Sheikh Zahir; Prihandoko, Rudi; Tobin, Andrew B; Milligan, Graeme

    2016-12-30

    G protein-coupled receptors (GPCRs) can initiate intracellular signaling cascades by coupling to an array of heterotrimeric G proteins and arrestin adaptor proteins. Understanding the contribution of each of these coupling options to GPCR signaling has been hampered by a paucity of tools to selectively perturb receptor function. Here we employ CRISPR/Cas9 genome editing to eliminate selected G proteins (Gαq and Gα11) or arrestin2 and arrestin3 from HEK293 cells together with the elimination of receptor phosphorylation sites to define the relative contribution of G proteins, arrestins, and receptor phosphorylation to the signaling outcomes of the free fatty acid receptor 4 (FFA4). A lack of FFA4-mediated elevation of intracellular Ca(2+) in Gαq/Gα11-null cells and agonist-mediated receptor internalization in arrestin2/3-null cells confirmed previously reported canonical signaling features of this receptor, thereby validating the genome-edited HEK293 cells. FFA4-mediated ERK1/2 activation was totally dependent on Gq/11 but intriguingly was substantially enhanced for FFA4 receptors lacking sites of regulated phosphorylation. This was not due to a simple lack of desensitization of Gq/11 signaling because the Gq/11-dependent calcium response was desensitized by both receptor phosphorylation and arrestin-dependent mechanisms, whereas a substantially enhanced ERK1/2 response was only observed for receptors lacking phosphorylation sites and not in arrestin2/3-null cells. In conclusion, we validate CRISPR/Cas9 engineered HEK293 cells lacking Gq/11 or arrestin2/3 as systems for GPCR signaling research and employ these cells to reveal a previously unappreciated interplay of signaling pathways where receptor phosphorylation can impact on ERK1/2 signaling through a mechanism that is likely independent of arrestins.

  9. Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling*

    PubMed Central

    Alvarez-Curto, Elisa; Inoue, Asuka; Jenkins, Laura; Raihan, Sheikh Zahir; Prihandoko, Rudi; Tobin, Andrew B.

    2016-01-01

    G protein-coupled receptors (GPCRs) can initiate intracellular signaling cascades by coupling to an array of heterotrimeric G proteins and arrestin adaptor proteins. Understanding the contribution of each of these coupling options to GPCR signaling has been hampered by a paucity of tools to selectively perturb receptor function. Here we employ CRISPR/Cas9 genome editing to eliminate selected G proteins (Gαq and Gα11) or arrestin2 and arrestin3 from HEK293 cells together with the elimination of receptor phosphorylation sites to define the relative contribution of G proteins, arrestins, and receptor phosphorylation to the signaling outcomes of the free fatty acid receptor 4 (FFA4). A lack of FFA4-mediated elevation of intracellular Ca2+ in Gαq/Gα11-null cells and agonist-mediated receptor internalization in arrestin2/3-null cells confirmed previously reported canonical signaling features of this receptor, thereby validating the genome-edited HEK293 cells. FFA4-mediated ERK1/2 activation was totally dependent on Gq/11 but intriguingly was substantially enhanced for FFA4 receptors lacking sites of regulated phosphorylation. This was not due to a simple lack of desensitization of Gq/11 signaling because the Gq/11-dependent calcium response was desensitized by both receptor phosphorylation and arrestin-dependent mechanisms, whereas a substantially enhanced ERK1/2 response was only observed for receptors lacking phosphorylation sites and not in arrestin2/3-null cells. In conclusion, we validate CRISPR/Cas9 engineered HEK293 cells lacking Gq/11 or arrestin2/3 as systems for GPCR signaling research and employ these cells to reveal a previously unappreciated interplay of signaling pathways where receptor phosphorylation can impact on ERK1/2 signaling through a mechanism that is likely independent of arrestins. PMID:27852822

  10. [Near infrared spectroscopy study on water content in turbine oil].

    PubMed

    Chen, Bin; Liu, Ge; Zhang, Xian-Ming

    2013-11-01

    Near infrared (NIR) spectroscopy combined with successive projections algorithm (SPA) was investigated for determination of water content in turbine oil. Through the 57 samples of different water content in turbine oil scanned applying near infrared (NIR) spectroscopy, with the water content in the turbine oil of 0-0.156%, different pretreatment methods such as the original spectra, first derivative spectra and differential polynomial least squares fitting algorithm Savitzky-Golay (SG), and successive projections algorithm (SPA) were applied for the extraction of effective wavelengths, the correlation coefficient (R) and root mean square error (RMSE) were used as the model evaluation indices, accordingly water content in turbine oil was investigated. The results indicated that the original spectra with different water content in turbine oil were pretreated by the performance of first derivative + SG pretreatments, then the selected effective wavelengths were used as the inputs of least square support vector machine (LS-SVM). A total of 16 variables selected by SPA were employed to construct the model of SPA and least square support vector machine (SPA-LS-SVM). There is 9 as The correlation coefficient was 0.975 9 and the root of mean square error of validation set was 2.655 8 x 10(-3) using the model, and it is feasible to determine the water content in oil using near infrared spectroscopy and SPA-LS-SVM, and an excellent prediction precision was obtained. This study supplied a new and alternative approach to the further application of near infrared spectroscopy in on-line monitoring of contamination such as water content in oil.

  11. Mathematics Education Research in Turkey: A Content Analysis Study

    ERIC Educational Resources Information Center

    Ciltas, Alper; Guler, Gursel; Sozbilir, Mustafa

    2012-01-01

    In this study, a content analysis of research is aimed in the field of mathematics education of Turkish researchers. To this aim, the investigation of 359 article were made which were accessed from web in full text between 1987 and 2009 years and which were published in the field of mathematics education from 32 different journals. 27 of these…

  12. Undergraduate Knowledge of Aging: A Comparative Study of Biopsychosocial Content

    ERIC Educational Resources Information Center

    Damron-Rodriguez, JoAnn; Funderburk, Brooke; Lee, Martin; Solomon, David H.

    2004-01-01

    This study assesses undergraduate knowledge of aging, distinguishing between types of deficits (ignorance vs. misinformation) and content areas as delineated by a biopsychosocial framework. Knowledge is examined as an outcome of taking an aging elective, while accounting for course rating and knowledge retention. A diverse body of UCLA…

  13. 23 CFR 650.117 - Content of design studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Content of design studies. 650.117 Section 650.117 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Location and Hydraulic Design of Encroachments on Flood Plains §...

  14. 23 CFR 650.117 - Content of design studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Content of design studies. 650.117 Section 650.117 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Location and Hydraulic Design of Encroachments on Flood Plains §...

  15. 23 CFR 650.117 - Content of design studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Content of design studies. 650.117 Section 650.117 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Location and Hydraulic Design of Encroachments on Flood Plains §...

  16. 23 CFR 650.117 - Content of design studies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Content of design studies. 650.117 Section 650.117 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Location and Hydraulic Design of Encroachments on Flood Plains §...

  17. 23 CFR 650.117 - Content of design studies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Content of design studies. 650.117 Section 650.117 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Location and Hydraulic Design of Encroachments on Flood Plains §...

  18. Container-content compatibility studies: a pharmaceutical team's integrated approach.

    PubMed

    Laschi, Alda; Sehnal, Natacha; Alarcon, Antoine; Barcelo, Beatrice; Caire-Maurisier, François; Delaire, Myriam; Feuilloley, Marc; Genot, Stéphanie; Lacaze, Catherine; Pisarik, Luc; Smati, Christophe

    2009-01-01

    Container-content compatibility studies are required as part of the submission of a new product market authorization file or for a change relating to the primary product-contact packaging. Many regulatory publications and guidances are available in the USA, Europe, and Japan. However these publications and guidances are not sufficiently precise enough to allow for consistent interpretation and implementation of the technical requirements. A working group has been formed by the French Society of Pharmaceutical Science and Technology (SFSTP) in order to propose guidance for container-content interaction studies that meet both European and US requirements, and allows consistent and standardized information to be presented by the industry to the regulators. When a pharmaceutical drug product remains in prolonged contact with a material, the two critical points to consider are the drug product's quality and safety. A pharmaceutical evaluation of the container-content relationship should be done based on the knowledge of the contact material (e.g., type, physicochemical properties), its manufacturing processes (e.g., the type of sterilization that could potentially alter the interactions), and the formulation components involved in contact with this material (e.g., physicochemical properties, pharmaceutical presentation, route of administration). Quality is evaluated using the stability study performed on the product. Safety is partially evaluated with the stability study and is analyzed in conjunction with toxicity testing, specifically with cytotoxicity testing. The toxicity aspect is the key point of the container-content compatibility study and of patient safety. Migration tests are conducted when an interaction is suspected, or found based on previous results, to identify the component responsible for this interaction and to help select a new material if needed. Therefore, such tests are perhaps not the best ones to use for the purpose of safety evaluation

  19. Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling

    PubMed Central

    Zindel, Diana; Engel, Sandra; Bottrill, Andrew R.; Pin, Jean-Philippe; Prézeau, Laurent; Tobin, Andrew B.; Bünemann, Moritz; Krasel, Cornelius; Butcher, Adrian J.

    2016-01-01

    The parathyroid hormone receptor 1 (PTH1R) is a member of family B of G-protein-coupled receptors (GPCRs), predominantly expressed in bone and kidney where it modulates extracellular Ca2+ homeostasis and bone turnover. It is well established that phosphorylation of GPCRs constitutes a key event in regulating receptor function by promoting arrestin recruitment and coupling to G-protein-independent signaling pathways. Mapping phosphorylation sites on PTH1R would provide insights into how phosphorylation at specific sites regulates cell signaling responses and also open the possibility of developing therapeutic agents that could target specific receptor functions. Here, we have used mass spectrometry to identify nine sites of phosphorylation in the C-terminal tail of PTH1R. Mutational analysis revealed identified two clusters of serine and threonine residues (Ser489–Ser495 and Ser501–Thr506) specifically responsible for the majority of PTH(1–34)-induced receptor phosphorylation. Mutation of these residues to alanine did not affect negatively on the ability of the receptor to couple to G-proteins or activate extracellular-signal-regulated kinase 1/2. Using fluorescence resonance energy transfer and bioluminescence resonance energy transfer to monitor PTH(1–34)-induced interaction of PTH1R with arrestin3, we show that the first cluster Ser489–Ser495 and the second cluster Ser501–Thr506 operated in concert to mediate both the efficacy and potency of ligand-induced arrestin3 recruitment. We further demonstrate that Ser503 and Thr504 in the second cluster are responsible for 70% of arrestin3 recruitment and are key determinants for interaction of arrestin with the receptor. Our data are consistent with the hypothesis that the pattern of C-terminal tail phosphorylation on PTH1R may determine the signaling outcome following receptor activation. PMID:27623777

  20. Concomitant Action of Structural Elements and Receptor Phosphorylation Determines Arrestin-3 Interaction with the Free Fatty Acid Receptor FFA4*

    PubMed Central

    Butcher, Adrian J.; Hudson, Brian D.; Shimpukade, Bharat; Alvarez-Curto, Elisa; Prihandoko, Rudi; Ulven, Trond; Milligan, Graeme; Tobin, Andrew B.

    2014-01-01

    In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr347, Thr349, Ser350, Ser357, and Ser360) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu341, Asp348, and Asp355 located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling. PMID:24817122

  1. Distinct Phosphorylation Sites on the β2-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of β-Arrestin

    PubMed Central

    Nobles, Kelly N.; Xiao, Kunhong; Ahn, Seungkirl; Shukla, Arun K.; Lam, Christopher M.; Rajagopal, Sudarshan; Strachan, Ryan T.; Huang, Teng-Yi; Bressler, Erin A.; Hara, Makoto R.; Shenoy, Sudha K.; Gygi, Steven P.; Lefkowitz, Robert J.

    2012-01-01

    Phosphorylation of G protein–coupled receptors (GPCRs, which are also known as seven-transmembrane spanning receptors) by GPCR kinases (GRKs) plays essential roles in the regulation of receptor function by promoting interactions of the receptors with β-arrestins. These multifunctional adaptor proteins desensitize GPCRs, by reducing receptor coupling to G proteins and facilitating receptor internalization, and mediate GPCR signaling through β-arrestin–specific pathways. Detailed mapping of the phosphorylation sites on GPCRs targeted by individual GRKs and an understanding of how these sites regulate the specific functional consequences of β-arrestin engagement may aid in the discovery of therapeutic agents targeting individual β-arrestin functions. The β2-adrenergic receptor (β2AR) has many serine and threonine residues in the carboxyl-terminal tail and the intracellular loops, which are potential sites of phosphorylation. We monitored the phosphorylation of the β2AR at specific sites upon stimulation with an agonist that promotes signaling by both G protein–mediated and β-arrestin–mediated pathways or with a biased ligand that promotes signaling only through β-arrestin–mediated events in the presence of the full complement of GRKs or when either GRK2 or GRK6 was depleted. We correlated the specific and distinct patterns of receptor phosphorylation by individual GRKs with the functions of β-arrestins and propose that the distinct phosphorylation patterns established by different GRKs establish a “barcode” that imparts distinct conformations to the recruited β-arrestin, thus regulating its functional activities. PMID:21868357

  2. Visual Arrestin 1 Contributes to Cone Photoreceptor Survival and Light Adaptation

    PubMed Central

    Brown, Bruce M.; Ramirez, Teresa; Rife, Lawrence

    2010-01-01

    Purpose. To evaluate morphologic and functional contributions of Arrestin 1 (Arr1) and Arrestin 4 (Arr4) in cone photoreceptors, the authors examined the phenotypes of visual arrestin knockout mice (Arr1−/−, Arr4−/−, Arr1−/−Arr4−/− [Arr-DKO]) reared in darkness. Methods. Retinal rods and cones were evaluated in wild-type (WT), Arr1−/−, Arr4−/−, and Arr-DKO mice using quantitative morphologic analysis, immunoblot, immunohistochemistry, TUNEL, and electroretinographic (ERG) techniques. Results. Compared with either Arr4−/− or WT, Arr1−/− and Arr-DKO mice had increased apoptotic nuclei in their retinal outer nuclear layer (ONL) at postnatal day (P) 22. By P60, cone density was significantly diminished, but the ONL appeared normal. After 1 minute of background illumination, cone ERG b-wave amplitudes were similar in WT and all Arr KO mice. However, by 3 minutes and continuing through 15 minutes of light adaptation, the cone b-wave amplitudes of WT and Arr4−/− mice increased significantly over those of the Arr1−/− and Arr-DKO mice, which demonstrated no cone b-wave amplitude increase. In contrast, ERG flicker analysis after the 15-minute light adaptation period demonstrated no loss in amplitude for either Arr1−/− or Arr4−/− mice, whereas Arr-DKO had significantly lower amplitudes. When Arr1 expression was restored in Arr1−/− mice (+p48Arr1−/−), normal cone density and light-adapted ERG b-wave amplitudes were observed. Conclusions. In the adult dark-reared Arr1−/− and Arr-DKO mice, viable cones diminish over time. Arr1 expression is essential for cone photoreceptor survival and light adaptation, whereas either Arr1 or Arr4 is necessary for maintaining normal flicker responses. PMID:20019357

  3. Content-Related Interactions in Self-initiated Study Groups

    NASA Astrophysics Data System (ADS)

    Christian, Karen; Talanquer, Vicente

    2012-09-01

    The central goal of the present exploratory study was to investigate the nature of the content-related interactions in study groups independently organized by college organic chemistry students. We were particularly interested in the identification of the different factors that affected the emergence of opportunities for students to co-construct understanding and engage in higher levels of cognitive processing. Our results are based on the analysis of in situ observations of 34 self-initiated study sessions involving over a 100 students in three academic semesters. The investigation revealed three major types of social regulation processes, teaching, tutoring, and co-construction in the observed study sessions. However, the extent to which students engaged in each of them varied widely from one session to another. This variability was mostly determined by the specific composition of the study groups and the nature of the study tasks in which they were engaged. Decisions about how to organize the study session, the relative content knowledge and conceptual understanding expressed by the participants, as well as the cognitive level of the problems that guided group work had a strong impact on the nature of student interactions. Nevertheless, group talk in the observed study groups was mostly focused on low-level cognitive processes. The results of our work provide insights on how to better support students' productive engagement in study groups.

  4. Non-Hematopoietic β-Arrestin1 Confers Protection Against Experimental Colitis.

    PubMed

    Lee, Taehyung; Lee, Eunhee; Arrollo, David; Lucas, Peter C; Parameswaran, Narayanan

    2016-05-01

    β-Arrestins are multifunctional scaffolding proteins that modulate G protein-coupled receptor (GPCR)-dependent and -independent cell signaling pathways in various types of cells. We recently demonstrated that β-arrestin1 (β-arr1) deficiency strikingly attenuates dextran sodium sulfate (DSS)-induced colitis in mice. Since DSS-induced colitis is in part dependent on gut epithelial injury, we examined the role of β-arr1 in intestinal epithelial cells (IECs) using a colon epithelial cell line, SW480 cells. Surprisingly, we found that knockdown of β-arr1 in SW480 cells enhanced epithelial cell death via a caspase-3-dependent process. To understand the in vivo relevance and potential cell type-specific role of β-arr1 in colitis development, we generated bone marrow chimeras with β-arr1 deficiency in either the hematopoietic or non-hematopoietic compartment. Reconstituted chimeric mice were then subjected to DSS-induced colitis. Similar to our previous findings, β-arr1 deficiency in the hematopoietic compartment protected mice from DSS-induced colitis. However, consistent with the role of β-arr1 in epithelial apoptosis in vitro, non-hematopoietic β-arr1 deficiency led to an exacerbated colitis phenotype. To further understand signaling mechanisms, we examined the effect of β-arr1 on TNF-α-mediated NFκB and MAPK pathways. Our results demonstrate that β-arr1 has a critical role in modulating ERK, JNK and p38 MAPK pathways mediated by TNF-α in IECs. Together, our results show that β-arr1-dependent signaling in hematopoietic and non-hematopoietic cells differentially regulates colitis pathogenesis and further demonstrates that β-arr1 in epithelial cells inhibits TNF-α-induced cell death pathways.

  5. Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods.

    PubMed

    Frederiksen, Rikard; Nymark, Soile; Kolesnikov, Alexander V; Berry, Justin D; Adler, Leopold; Koutalos, Yiannis; Kefalov, Vladimir J; Cornwall, M Carter

    2016-07-01

    Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1(-/-)), Arr1-deficient (Arr1(-/-)), and Arr1-overexpressing (Arr1(ox)) mice. We find that in WT mouse rods, Meta III peaks ∼6 min after rhodopsin activation and decays with a time constant (τ) of 17 min. Meta III decay slows in Arr1(-/-) rods (τ of ∼27 min), whereas it accelerates in Arr1(ox) rods (τ of ∼8 min) and Grk1(-/-) rods (τ of ∼13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo.

  6. Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model

    PubMed Central

    Chen, Minyong; Hegde, Akhil; Choi, Yeon Ho; Theriot, Barbara S.; Premont, Richard T.; Chen, Wei

    2015-01-01

    β-Arrestin-2 (βarr2) is a ubiquitously expressed cytosolic protein that terminates G protein–coupled receptor signaling and transduces G protein–independent signaling. We previously showed that mice lacking βarr2 do not develop an asthma phenotype when sensitized to, and challenged with, allergens. The current study evaluates if an established asthma phenotype can be mitigated by deletion of βarr2 using an inducible Cre recombinase. We sensitized and challenged mice to ovalbumin (OVA) and demonstrated that on Day (d) 24 the allergic asthma phenotype was apparent in uninduced βarr2 and wild-type (WT) mice. In a second group of OVA-treated mice, tamoxifen was injected on d24 to d28 to activate Cre recombinase, and OVA aerosol challenge was continued through d44. The asthma phenotype was assessed using lung mechanics measurements, bronchoalveolar lavage cell analysis, and histological assessment of mucin and airway inflammation. Compared with their respective saline-treated controls, OVA-treated WT mice and mice expressing the inducible Cre recombinase displayed a significant asthma phenotype at d45. Whereas tamoxifen treatment had no significant effect on the asthma phenotype in WT mice, it inhibited βarr2 expression and caused a significant reduction in airway hyper-responsiveness (AHR) in Cre-inducible mice. These findings suggest that βarr2 is actively required for perpetuation of the AHR component of the allergic asthma phenotype. Our finding that βarr2 participates in the perpetuation of AHR in an asthma model means that targeting βarr2 may provide immediate and potentially long-term relief from daily asthma symptoms due to AHR irrespective of inflammation. PMID:25569510

  7. Visual Arrestin 1 Acts as a Modulator for N-Ethylmaleimide Sensitive Factor in the Photoreceptor Synapse

    PubMed Central

    Huang, Shun-Ping; Brown, Bruce M.; Craft, Cheryl M.

    2010-01-01

    In the G-protein coupled receptor (GPCR) phototransduction cascade, visual Arrestin1 (Arr1) binds to and deactivates phosphorylated light-activated opsins, a process that is critical for effective recovery and normal vision. In this report, we discovered a novel synaptic interaction between Arr1 and N-ethylmaleimide sensitive factor (NSF) that is enhanced in a dark environment when mouse photoreceptors are depolarized and the rate of exocytosis is elevated. In the photoreceptor synapse, NSF functions to sustain a higher rate of exocytosis, in addition to the compensatory endocytosis to retrieve and to recycle vesicle membrane and synaptic proteins. Not only does Arr1 bind to the junction of NSF N-terminal and its first ATPase domains in an ATP-dependent manner in vitro, but Arr1 also enhances both NSF ATPase and NSF disassembly activities. In vivo experiments in mouse retinas with the Arr1 gene knocked out, the expression levels of NSF and other synapse-enriched components, including vesicular glutamate transporter 1 (vGLUT1), excitatory amino acid transporter 5 (EAAT5), and vesicle associated membrane protein 2 (VAMP2), are markedly reduced, which lead to a substantial decrease in the exocytosis rate with FM1-43. Thus, we propose that the Arr1 and NSF interaction is important for modulating normal synaptic function in mouse photoreceptors. This study demonstrates a vital alternative function for Arr1 in the photoreceptor synapse and provides key insights into the potential molecular mechanisms of inherited retinal diseases, such as Oguchi disease and Arr1-associated retinitis pigmentosa. PMID:20631167

  8. Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods

    PubMed Central

    Nymark, Soile; Kolesnikov, Alexander V.; Berry, Justin D.; Adler, Leopold; Koutalos, Yiannis; Kefalov, Vladimir J.; Cornwall, M. Carter

    2016-01-01

    Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1−/−), Arr1-deficient (Arr1−/−), and Arr1-overexpressing (Arr1ox) mice. We find that in WT mouse rods, Meta III peaks ∼6 min after rhodopsin activation and decays with a time constant (τ) of 17 min. Meta III decay slows in Arr1−/− rods (τ of ∼27 min), whereas it accelerates in Arr1ox rods (τ of ∼8 min) and Grk1−/− rods (τ of ∼13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo. PMID:27353443

  9. The Prostaglandin E2 Receptor, EP2, Stimulates Keratinocyte Proliferation in Mouse Skin by G Protein-dependent and β-Arrestin1-dependent Signaling Pathways*

    PubMed Central

    Chun, Kyung-Soo; Lao, Huei-Chen; Langenbach, Robert

    2010-01-01

    The prostaglandin E2 (PGE2) G protein-coupled receptor (GPCR), EP2, plays important roles in mouse skin tumor development (Chun, K. S., Lao, H. C., Trempus, C. S., Okada, M., and Langenbach, R. (2009) Carcinogenesis 30, 1620–1627). Because keratinocyte proliferation is essential for skin tumor development, EP2-mediated signaling pathways that contribute to keratinocyte proliferation were investigated. A single topical application of the EP2 agonist, butaprost, dose-dependently increased keratinocyte replication via activation of epidermal growth factor receptor (EGFR) and PKA signaling. Because GPCR-mediated activation of EGFR can involve the formation of a GPCR-β-arrestin-Src signaling complex, the possibility of a β-arrestin1-Src complex contributing to EP2-mediated signaling in keratinocytes was investigated. Butaprost induced β-arrestin1-Src complex formation and increased both Src and EGFR activation. A role for β-arrestin1 in EP2-mediated Src and EGFR activation was demonstrated by the observation that β-arrestin1 deficiency significantly reduced Src and EGFR activation. In agreement with a β-arrestin1-Src complex contributing to EGFR activation, Src and EGFR inhibition (PP2 and AG1478, respectively) indicated that Src was upstream of EGFR. Butaprost also induced the activation of Akt, ERK1/2, and STAT3, and both β-arrestin1 deficiency and EGFR inhibition (AG1478 or gefitinib) decreased their activation. In addition to β-arrestin1-dependent EGFR activation, butaprost increased PKA activation, as measured by phospho-GSK3β (p-GSK3β) and p-cAMP-response element-binding protein formation. PKA inhibition (H89 or RP-adenosine-3′,5′-cyclic monophosphorothioate (RP-cAMPS)) decreased butaprost-induced cAMP-response element-binding protein and ERK activation but did not affect EGFR activation, whereas β-arrestin1 deficiency decreased EGFR activation but did not affect butaprost-induced PKA activation, thus indicating that they were independent EP2

  10. The prostaglandin E2 receptor, EP2, stimulates keratinocyte proliferation in mouse skin by G protein-dependent and {beta}-arrestin1-dependent signaling pathways.

    PubMed

    Chun, Kyung-Soo; Lao, Huei-Chen; Langenbach, Robert

    2010-12-17

    The prostaglandin E(2) (PGE(2)) G protein-coupled receptor (GPCR), EP2, plays important roles in mouse skin tumor development (Chun, K. S., Lao, H. C., Trempus, C. S., Okada, M., and Langenbach, R. (2009) Carcinogenesis 30, 1620-1627). Because keratinocyte proliferation is essential for skin tumor development, EP2-mediated signaling pathways that contribute to keratinocyte proliferation were investigated. A single topical application of the EP2 agonist, butaprost, dose-dependently increased keratinocyte replication via activation of epidermal growth factor receptor (EGFR) and PKA signaling. Because GPCR-mediated activation of EGFR can involve the formation of a GPCR-β-arrestin-Src signaling complex, the possibility of a β-arrestin1-Src complex contributing to EP2-mediated signaling in keratinocytes was investigated. Butaprost induced β-arrestin1-Src complex formation and increased both Src and EGFR activation. A role for β-arrestin1 in EP2-mediated Src and EGFR activation was demonstrated by the observation that β-arrestin1 deficiency significantly reduced Src and EGFR activation. In agreement with a β-arrestin1-Src complex contributing to EGFR activation, Src and EGFR inhibition (PP2 and AG1478, respectively) indicated that Src was upstream of EGFR. Butaprost also induced the activation of Akt, ERK1/2, and STAT3, and both β-arrestin1 deficiency and EGFR inhibition (AG1478 or gefitinib) decreased their activation. In addition to β-arrestin1-dependent EGFR activation, butaprost increased PKA activation, as measured by phospho-GSK3β (p-GSK3β) and p-cAMP-response element-binding protein formation. PKA inhibition (H89 or R(P)-adenosine-3',5'-cyclic monophosphorothioate (R(P)-cAMPS)) decreased butaprost-induced cAMP-response element-binding protein and ERK activation but did not affect EGFR activation, whereas β-arrestin1 deficiency decreased EGFR activation but did not affect butaprost-induced PKA activation, thus indicating that they were independent EP2

  11. Content and Workflow Management for Library Websites: Case Studies

    ERIC Educational Resources Information Center

    Yu, Holly, Ed.

    2005-01-01

    Using database-driven web pages or web content management (WCM) systems to manage increasingly diverse web content and to streamline workflows is a commonly practiced solution recognized in libraries today. However, limited library web content management models and funding constraints prevent many libraries from purchasing commercially available…

  12. The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.

    PubMed

    Dores, Michael R; Lin, Huilan; J Grimsey, Neil; Mendez, Francisco; Trejo, JoAnn

    2015-12-15

    The sorting of G protein-coupled receptors (GPCRs) to lysosomes is critical for proper signaling and cellular responses. We previously showed that the adaptor protein ALIX regulates lysosomal degradation of protease-activated receptor-1 (PAR1), a GPCR for thrombin, independent of ubiquitin-binding ESCRTs and receptor ubiquitination. However, the mechanisms that regulate ALIX function during PAR1 lysosomal sorting are not known. Here we show that the mammalian α-arrestin arrestin domain-containing protein-3 (ARRDC3) regulates ALIX function in GPCR sorting via ubiquitination. ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. Depletion of ARRDC3 by small interfering RNA disrupts ALIX interaction with activated PAR1 and the CHMP4B ESCRT-III subunit, suggesting that ARRDC3 regulates ALIX activity. We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1. A screen of nine mammalian NEDD4-family E3 ubiquitin ligases revealed a critical role for WWP2. WWP2 interacts with ARRDC3 and not ALIX. Depletion of WWP2 inhibited ALIX ubiquitination and blocked ALIX interaction with activated PAR1 and CHMP4B. These findings demonstrate a new role for the α-arrestin ARRDC3 and the E3 ubiquitin ligase WWP2 in regulation of ALIX ubiquitination and lysosomal sorting of GPCRs.

  13. ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia

    PubMed Central

    Wang, Pei; Xu, Tian-Ying; Wei, Kai; Guan, Yun-Feng; Wang, Xia; Xu, Hui; Su, Ding-Feng; Pei, Gang; Miao, Chao-Yu

    2014-01-01

    Autophagy, a highly conserved process conferring cytoprotection against stress, contributes to the progression of cerebral ischemia. β-arrestins are multifunctional proteins that mediate receptor desensitization and serve as important signaling scaffolds involved in numerous physiopathological processes. Here, we show that both ARRB1 (arrestin, β 1) and ARRB2 (arrestin, β 2) were upregulated by cerebral ischemic stress. Knockout of Arrb1, but not Arrb2, aggravated the mortality, brain infarction, and neurological deficit in a mouse model of cerebral ischemia. Accordingly, Arrb1-deficient neurons exhibited enhanced cell injury upon oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Deletion of Arrb1 did not affect the cerebral ischemia-induced inflammation, oxidative stress, and nicotinamide phosphoribosyltransferase upregulation, but markedly suppressed autophagy and induced neuronal apoptosis/necrosis in vivo and in vitro. Additionally, we found that ARRB1 interacted with BECN1/Beclin 1 and PIK3C3/Vps34, 2 major components of the BECN1 autophagic core complex, under the OGD condition but not normal conditions in neurons. Finally, deletion of Arrb1 impaired the interaction between BECN1 and PIK3C3, which is a critical event for autophagosome formation upon ischemic stress, and markedly reduced the kinase activity of PIK3C3. These findings reveal a neuroprotective role for ARRB1, in the context of cerebral ischemia, centered on the regulation of BECN1-dependent autophagosome formation. PMID:24988431

  14. Casein kinase 1 controls the activation threshold of an α-arrestin by multisite phosphorylation of the interdomain hinge

    PubMed Central

    Herrador, Antonio; Livas, Daniela; Soletto, Lucía; Becuwe, Michel; Léon, Sébastien; Vincent, Olivier

    2015-01-01

    α-Arrestins play a key role as trafficking adaptors in both yeast and mammals. The yeast Rim8/Art9 α-arrestin mediates the recruitment of endosomal sorting complex required for transport (ESCRT) to the seven-transmembrane protein Rim21 in the ambient pH signaling RIM pathway. ESCRT is believed to function as a signaling platform that enables the proteolytic activation of the Rim101 transcription factor upon external alkalization. Here we provide evidence that the pH signal promotes the stable association of Rim8 with Rim21 at the plasma membrane. We show that Rim8 is phosphorylated in a pH-independent but Rim21-dependent manner by the plasma membrane–associated casein kinase 1 (CK1). We further show that this process involves a cascade of phosphorylation events within the hinge region connecting the arrestin domains. Strikingly, loss of casein kinase 1 activity causes constitutive activation of the RIM pathway, and, accordingly, pH signaling is activated in a phosphodeficient Rim8 mutant and impaired in the corresponding phosphomimetic mutant. Our results indicate that Rim8 phosphorylation prevents its accumulation at the plasma membrane at acidic pH and thereby inhibits RIM signaling. These findings support a model in which CK1-mediated phosphorylation of Rim8 contributes to setting a signaling threshold required to inhibit the RIM pathway at acidic pH. PMID:25851600

  15. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions

    PubMed Central

    Zhu, Lu; Almaça, Joana; Dadi, Prasanna K.; Hong, Hao; Sakamoto, Wataru; Rossi, Mario; Lee, Regina J.; Vierra, Nicholas C.; Lu, Huiyan; Cui, Yinghong; McMillin, Sara M.; Perry, Nicole A.; Gurevich, Vsevolod V.; Lee, Amy; Kuo, Bryan; Leapman, Richard D.; Matschinsky, Franz M.; Doliba, Nicolai M.; Urs, Nikhil M.; Caron, Marc G.; Jacobson, David A.; Caicedo, Alejandro; Wess, Jürgen

    2017-01-01

    β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function. PMID:28145434

  16. Working experiences of Iranian retired nurses: a content analysis study.

    PubMed

    Nobahar, Monir; Ahmadi, Fazlollah; Alhani, Fatemah; Fallahi Khoshknab, Masood

    2013-10-01

    Understanding the experiences of retired nurses can be useful in increasing self-confidence, motivation to work and work enthusiasm among nurses. The purpose of this study was to explore the work experiences of Iranian retired nurses. A qualitative design was conducted using a content analysis approach. Purposive sampling was used to choose the study participants. Semi-structured interviews were held to collect the perspectives of 20 retired nurses (10 female and 10 male). Two main themes emerged in the data analysis: 'work problems and unpleasant experiences in a sense' with subthemes 'exhausting work', 'insufficient salary', 'inappropriate relation' and 'unsuitable social position'; and 'job satisfaction and pleasant experiences in a sense' with subthemes 'divine satisfaction and religious belief', 'satisfaction of patients and their companions' and 'love of nursing profession and relaxation experience'. The findings indicate the challenges that nurses face after retirement. These experiences will help nurse managers to adopt appropriate measures to support nurses after retirement.

  17. Study of the detail content of Apollo orbital photography

    NASA Technical Reports Server (NTRS)

    Kinzly, R. E.

    1972-01-01

    The results achieved during a study of the Detail Content of Apollo Orbital Photography are reported. The effect of residual motion smear or image reproduction processes upon the detail content of lunar surface imagery obtained from the orbiting command module are assessed. Data and conclusions obtained from the Apollo 8, 12, 14 and 15 missions are included. For the Apollo 8, 12 and 14 missions, the bracket-mounted Hasselblad camera had no mechanism internal to the camera for motion compensation. If the motion of the command module were left totally uncompensated, these photographs would exhibit a ground smear varying from 12 to 27 meters depending upon the focal length of the lens and the exposure time. During the photographic sequences motion compensation was attempted by firing the attitude control system of the spacecraft at a rate to compensate for the motion relative to the lunar surface. The residual smear occurring in selected frames of imagery was assessed using edge analyses methods to obtain and achieved modulation transfer function (MTF) which was compared to a baseline MTF.

  18. G Protein-Coupled Receptor Kinase 3 and Protein Kinase C Phosphorylate the Distal C-Terminal Tail of the Chemokine Receptor CXCR4 and Mediate Recruitment of Beta-Arrestin.

    PubMed

    Luo, Jiansong; Busillo, John M; Stumm, Ralf; Benovic, Jeffrey L

    2017-03-22

    Phosphorylation of G protein-coupled receptors (GPCRs) is a key event for cell signaling and regulation of receptor function. Previously, using tandem mass spectrometry, we identified two phosphorylation sites at the distal C-terminal tail of the chemokine receptor CXCR4, but were unable to determine which specific residues were phosphorylated. Here, we demonstrate that serines 346 and/or 347 (Ser-346/7) of CXCR4 are phosphorylated upon stimulation with the agonist CXCL12 as well as a CXCR4 pepducin, ATI-2341. ATI-2341, a Gi-biased CXCR4 agonist, induced more robust phosphorylation of Ser-346/7 compared to CXCL12. Knockdown of GRK2, GRK3 or GRK6 reduced CXCL12-induced phosphorylation of Ser-346/7 with GRK3 knockdown having the strongest effect, while inhibition of the conventional PKC isoforms reduced phosphorylation of Ser-346/7 induced by either CXCL12 or ATI-2341. The loss of GRK3- or PKC-mediated phosphorylation of Ser-346/7 impaired the recruitment of β-arrestin to CXCR4. We also found that a pseudo-substrate peptide inhibitor for PKCζ effectively inhibited CXCR4 phosphorylation and signaling, most likely by functioning as a non-specific CXCR4 antagonist. Together, these studies demonstrate the role Ser-346/7 plays in arrestin recruitment and initiation of the process of receptor desensitization and provide insight into the dysregulation of CXCR4 observed in patients with various forms of WHIM syndrome.

  19. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    PubMed

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

  20. IRI related studies in Argentina: Topside profile and electron content

    NASA Astrophysics Data System (ADS)

    Ezquer, R. G.; Mosert, M.; Radicella, S. M.; Cabrera, M. A.

    This paper reviews and extends studies of the ability of the International Reference Ionosphere (IRI) to make predictions of the topside electron density (N) and the total electron content for low latitude locations. Members of the Argentine scientific community have performed the reported studies. Topside Profile: Measurements of N obtained with the Hinotori and Taiyo satellites were used to check the ability of the IRI to predict monthly average value of N at 600 km of altitude (N 600) in the low latitude region and, also, that corresponding to a particular day and time so-called "instanteneous N value". The comparison showed that the best agreement between IRI derived average N 600 values and measurements was obtained for a station near the magnetic equator and, in general, for the period of minimum ionisation for stations not near the magnetic equator. When ground ionosonde data obtained at Tucumán (26.9° S, 294.6°E; mag. latitude:-15.5) and Huancayo (12.0° S, 284.7° E; mag. latitude:-0.7) were used as input to the model the predicted instantaneous N 600 values were better than those obtained using either the CCIR or URSI options. Additional studies, covering different heights in the F region at low latitudes for low solar activity, showed that the IRI gives better N predictions than those obtained for high solar activity. Electron Content: Measurements of vertical total electron content (VTEC) over Tucumán, Havana (23.1° N, 277.5° E, mag. latitude: 34.2) and Arequipa (16.5° S, 289.0° E; geoma. Lat.:-5.1) obtained from geosynchronous and GPS satellites signals during high solar activity periods, have been used to study the IRI performance as predictor of TEC. Both versions, IRI-90 and IRI-95, overestimate VTEC at the southern crest of the equatorial anomaly for hours around the daily minimum, and underestimate it the rest of the day. This suggests that the main reason for the disagreement is the shape of the N profile assumed by the model. Good

  1. Arrestin-3 binds c-Jun N-terminal kinase 1 (JNK1) and JNK2 and facilitates the activation of these ubiquitous JNK isoforms in cells via scaffolding.

    PubMed

    Kook, Seunghyi; Zhan, Xuanzhi; Kaoud, Tamer S; Dalby, Kevin N; Gurevich, Vsevolod V; Gurevich, Eugenia V

    2013-12-27

    Non-visual arrestins scaffold mitogen-activated protein kinase (MAPK) cascades. The c-Jun N-terminal kinases (JNKs) are members of MAPK family. Arrestin-3 has been shown to enhance the activation of JNK3, which is expressed mainly in neurons, heart, and testes, in contrast to ubiquitous JNK1 and JNK2. Although all JNKs are activated by MKK4 and MKK7, both of which bind arrestin-3, the ability of arrestin-3 to facilitate the activation of JNK1 and JNK2 has never been reported. Using purified proteins we found that arrestin-3 directly binds JNK1α1 and JNK2α2, interacting with the latter comparably to JNK3α2. Phosphorylation of purified JNK1α1 and JNK2α2 by MKK4 or MKK7 is increased by arrestin-3. Endogenous arrestin-3 interacted with endogenous JNK1/2 in different cell types. Arrestin-3 also enhanced phosphorylation of endogenous JNK1/2 in intact cells upon expression of upstream kinases ASK1, MKK4, or MKK7. We observed a biphasic effect of arrestin-3 concentrations on phosphorylation of JNK1α1 and JNK2α2 both in vitro and in vivo. Thus, arrestin-3 acts as a scaffold, facilitating JNK1α1 and JNK2α2 phosphorylation by MKK4 and MKK7 via bringing JNKs and their activators together. The data suggest that arrestin-3 modulates the activity of ubiquitous JNK1 and JNK2 in non-neuronal cells, impacting the signaling pathway that regulates their proliferation and survival.

  2. Studying of tritium content in snowpack of Degelen mountain range.

    PubMed

    Turchenko, D V; Lukashenko, S N; Aidarkhanov, A O; Lyakhova, O N

    2014-06-01

    The paper presents the results of investigation of tritium content in the layers of snow located in the streambeds of the "Degelen" massif contaminated with tritium. The objects of investigation were selected watercourses Karabulak, Uzynbulak, Aktybai located beyond the "Degelen" site. We studied the spatial distribution of tritium relative to the streambed of watercourses and defined the borders of the snow cover contamination. In the centre of the creek watercourses the snow contamination in the surface layer is as high as 40 000 Bq/L. The values of the background levels of tritium in areas not related to the streambed, which range from 40 to 50 Bq/L. The results of snow cover measurements in different seasonal periods were compared. The main mechanisms causing tritium transfer in snow were examined and identified. The most important mechanism of tritium transfer in the streams is tritium emanation from ice or soil surface.

  3. β-arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism

    PubMed Central

    Fernández-Arenas, Elena; Calleja, Enrique; Martínez-Martín, Nadia; Gharbi, Severine I; Navajas, Rosana; García-Medel, Noel; Penela, Petronila; Alcamí, Antonio; Mayor, Federico; Albar, Juan P; Alarcón, Balbino

    2014-01-01

    T-cell receptors (TCR) recognize their antigen ligand at the interface between T cells and antigen-presenting cells, known as the immunological synapse (IS). The IS provides a means of sustaining the TCR signal which requires the continual supply of new TCRs. These are endocytosed and redirected from distal membrane locations to the IS. In our search for novel cytoplasmic effectors, we have identified β-arrestin-1 as a ligand of non-phosphorylated resting TCRs. Using dominant-negative and knockdown approaches we demonstrate that β-arrestin-1 is required for the internalization and downregulation of non-engaged bystander TCRs. Furthermore, TCR triggering provokes the β-arrestin-1-mediated downregulation of the G-protein coupled chemokine receptor CXCR4, but not of other control receptors. We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163. This mechanism allows the first triggered TCRs to deliver a stop migration signal, and to promote the internalization of distal TCRs and CXCR4 and their translocation to the IS. This receptor crosstalk mechanism is critical to sustain the TCR signal. PMID:24502978

  4. G-Protein/β-Arrestin-Linked Fluctuating Network of G-Protein-Coupled Receptors for Predicting Drug Efficacy and Bias Using Short-Term Molecular Dynamics Simulation

    PubMed Central

    Ichikawa, Osamu; Fujimoto, Kazushi; Yamada, Atsushi; Okazaki, Susumu; Yamazaki, Kazuto

    2016-01-01

    The efficacy and bias of signal transduction induced by a drug at a target protein are closely associated with the benefits and side effects of the drug. In particular, partial agonist activity and G-protein/β-arrestin-biased agonist activity for the G-protein-coupled receptor (GPCR) family, the family with the most target proteins of launched drugs, are key issues in drug discovery. However, designing GPCR drugs with appropriate efficacy and bias is challenging because the dynamic mechanism of signal transduction induced by ligand—receptor interactions is complicated. Here, we identified the G-protein/β-arrestin-linked fluctuating network, which initiates large-scale conformational changes, using sub-microsecond molecular dynamics (MD) simulations of the β2-adrenergic receptor (β2AR) with a diverse collection of ligands and correlation analysis of their G protein/β-arrestin efficacy. The G-protein-linked fluctuating network extends from the ligand-binding site to the G-protein-binding site through the connector region, and the β-arrestin-linked fluctuating network consists of the NPxxY motif and adjacent regions. We confirmed that the averaged values of fluctuation in the fluctuating network detected are good quantitative indexes for explaining G protein/β-arrestin efficacy. These results indicate that short-term MD simulation is a practical method to predict the efficacy and bias of any compound for GPCRs. PMID:27187591

  5. Functional competence of a partially engaged GPCR–β-arrestin complex

    PubMed Central

    Kumari, Punita; Srivastava, Ashish; Banerjee, Ramanuj; Ghosh, Eshan; Gupta, Pragya; Ranjan, Ravi; Chen, Xin; Gupta, Bhagyashri; Gupta, Charu; Jaiman, Deepika; Shukla, Arun K.

    2016-01-01

    G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors and drug targets. GPCR signalling and desensitization is critically regulated by β-arrestins (βarr). GPCR–βarr interaction is biphasic where the phosphorylated carboxyl terminus of GPCRs docks to the N-domain of βarr first and then seven transmembrane core of the receptor engages with βarr. It is currently unknown whether fully engaged GPCR–βarr complex is essential for functional outcomes or partially engaged complex can also be functionally competent. Here we assemble partially and fully engaged complexes of a chimeric β2V2R with βarr1, and discover that the core interaction is dispensable for receptor endocytosis, ERK MAP kinase binding and activation. Furthermore, we observe that carvedilol, a βarr biased ligand, does not promote detectable engagement between βarr1 and the receptor core. These findings uncover a previously unknown aspect of GPCR-βarr interaction and provide novel insights into GPCR signalling and regulatory paradigms. PMID:27827372

  6. Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs.

    PubMed

    Gurevich, Vsevolod V; Gurevich, Eugenia V

    2015-01-01

    Most proteins have multiple functions. Obviously, conventional methods of manipulating the level of the protein of interest in the cell, such as over-expression, knockout or knockdown, affect all of its functions simultaneously. The key advantage of these methods is that over-expression, knockout or knockdown does not require any knowledge of the molecular mechanisms of the function(s) of the protein of interest. The disadvantage is that these approaches are inadequate to elucidate the role of an individual function of the protein in a particular cellular process. An alternative is the use of re-engineered proteins, in which a single function is eliminated or enhanced. The use of mono-functional elements of a multi-functional protein can also yield cleaner answers. This approach requires detailed knowledge of the structural basis of each function of the protein in question. Thus, a lot of preliminary structure-function work is necessary to make it possible. However, when this information is available, replacing the protein of interest with a mutant in which individual functions are modified can shed light on the biological role of those particular functions. Here, we illustrate this point using the example of protein kinases, most of which have additional non-enzymatic functions, as well as arrestins, known multi-functional signaling regulators in the cell.

  7. G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics.

    PubMed

    Violin, Jonathan D; Dewire, Scott M; Barnes, William G; Lefkowitz, Robert J

    2006-11-24

    Receptor desensitization progressively limits responsiveness of cells to chronically applied stimuli. Desensitization in the continuous presence of agonist has been difficult to study with available assay methods. Here, we used a fluorescence resonance energy transfer-based live cell assay for the second messenger diacylglycerol to measure desensitization of a model seven-transmembrane receptor, the Gq-coupled angiotensin II type 1(A) receptor, expressed in human embryonic kidney 293 cells. In response to angiotensin II, we observed a transient diacylglycerol response reflecting activation and complete desensitization of the receptor within 2-5 min. By utilizing a variety of approaches including graded tetracycline-inducible receptor expression, mutated receptors, and overexpression or short interfering RNA-mediated silencing of putative components of the cellular desensitization machinery, we conclude that the rate and extent of receptor desensitization are critically determined by the following: receptor concentration in the plasma membrane; the presence of phosphorylation sites on the carboxyl terminus of the receptor; kinase activity of G protein-coupled receptor kinase 2, but not of G protein-coupled receptor kinases 3, 5, or 6; and stoichiometric expression of beta-arrestin. The findings introduce the use of the biosensor diacylglycerol reporter as a powerful means for studying Gq-coupled receptor desensitization and document that, at the levels of receptor overexpression commonly used in such studies, the properties of the desensitization process are markedly perturbed and do not reflect normal cellular physiology.

  8. Discovery and Characterization of a G Protein–Biased Agonist That Inhibits β-Arrestin Recruitment to the D2 Dopamine Receptor

    PubMed Central

    Chun, Lani S.; Moritz, Amy E.; Miller, Brittney N.; Doyle, Trevor B.; Conroy, Jennie L.; Padron, Adrian; Meade, Julie A.; Xiao, Jingbo; Hu, Xin; Dulcey, Andrés E.; Han, Yang; Duan, Lihua; Titus, Steve; Bryant-Genevier, Melanie; Barnaeva, Elena; Ferrer, Marc; Javitch, Jonathan A.; Beuming, Thijs; Shi, Lei; Southall, Noel T.; Marugan, Juan J.; Sibley, David R.

    2014-01-01

    A high-throughput screening campaign was conducted to interrogate a 380,000+ small-molecule library for novel D2 dopamine receptor modulators using a calcium mobilization assay. Active agonist compounds from the primary screen were examined for orthogonal D2 dopamine receptor signaling activities including cAMP modulation and β-arrestin recruitment. Although the majority of the subsequently confirmed hits activated all signaling pathways tested, several compounds showed a diminished ability to stimulate β-arrestin recruitment. One such compound (MLS1547; 5-chloro-7-[(4-pyridin-2-ylpiperazin-1-yl)methyl]quinolin-8-ol) is a highly efficacious agonist at D2 receptor–mediated G protein–linked signaling, but does not recruit β-arrestin as demonstrated using two different assays. This compound does, however, antagonize dopamine-stimulated β-arrestin recruitment to the D2 receptor. In an effort to investigate the chemical scaffold of MLS1547 further, we characterized a set of 24 analogs of MLS1547 with respect to their ability to inhibit cAMP accumulation or stimulate β-arrestin recruitment. A number of the analogs were similar to MLS1547 in that they displayed agonist activity for inhibiting cAMP accumulation, but did not stimulate β-arrestin recruitment (i.e., they were highly biased). In contrast, other analogs displayed various degrees of G protein signaling bias. These results provided the basis to use pharmacophore modeling and molecular docking analyses to build a preliminary structure-activity relationship of the functionally selective properties of this series of compounds. In summary, we have identified and characterized a novel G protein–biased agonist of the D2 dopamine receptor and identified structural features that may contribute to its biased signaling properties. PMID:24755247

  9. Dependence of seismoelectric amplitudes on water content - a field study

    NASA Astrophysics Data System (ADS)

    Strahser, M. H. P.; Matthey, P.-D.; Jouniaux, L.; Sailhac, P.

    2009-04-01

    In porous saturated media, seismic compressional waves can cause seismoelectric and seismoelectromagnetic signals through electrokinetic coupling. It has been observed that these measureable signals also occur in partially saturated media, but the theory is largely unknown for these circumstances. Seismoelectromagnetic tomography is expected to combine the sensitivity of electrical properties to water-content and permeability, to the high spatial resolution of seismic surveys. A better understanding of the physical processes and a reliable quantification of the conversion between seismic and electric energy are necessary and need to take into account the effect of water-content, especially for shallow subsurface investigations. In order to quantify seismoelectric signals with changing water content, we repeated seismoelectric and seismic measurements on the same profile in the Vosges Mountains during several months. The electrical resistivity was also monitored to take into account the water-content variations. We show that an exponential relation can be established between the seismoelectric amplitudes normalized with the seismic amplitudes and the resistivity which in turn is related to the saturation: Increasing resistivity (decreasing water content) leads to decreasing normalized seismoelectric amplitudes. These results imply that the electrokinetic coefficient should increase with water-saturation, as measured in laboratory, but not predicted by theory. This work was funded by CNRS and Université Louis Pasteur de Strasbourg.

  10. β-Arrestin 1’s Interaction with TC45 Attenuates Stat signaling by dephosphorylating Stat to inhibit antimicrobial peptide expression

    PubMed Central

    Sun, Jie-Jie; Yang, Hui-Ting; Niu, Guo-Juan; Feng, Xiao-Wu; Lan, Jiang-Feng; Zhao, Xiao-Fan; Wang, Jin-Xing

    2016-01-01

    Impaired phosphatase activity leads to the persistent activation of signal transducers and activators of transcription (Stat). In mammals, Stat family members are often phosphorylated or dephosphorylated by the same enzymes. To date, only one Stat similar to mammalian Stat5a/b has been found in crustaceans and there have been few studies in Stat signal regulation in crustaceans. Here, we report that β-arrestin1 interacts with TC45 (45-kDa form of T cell protein tyrosine phosphatase) in the nucleus to attenuate Stat signaling by promoting dephosphorylation of Stat. Initially, we showed that Stat translocates into the nucleus to induce antimicrobial peptide (AMP) expression after bacterial infection. βArr1 enters the nucleus of hemocytes and recruits TC45 to form the βarr1-TC45-Stat complex, which dephosphorylates Stat efficiently. The interaction of TC45 with Stat decreased and Stat phosphorylation increased in βarr1-silenced shrimp (Marsupenaeus japonicus) after challenge with Vibrio anguillarum. βArr1 directly interacts with Stat in nucleus and accelerates Stat dephosphorylation by recruiting TC45 after V. anguillarum challenge. Further study showed that βarr1 and TC45 also affect AMP expression, which is regulated by Stat. Therefore, βarr1 and TC45 are involved in the anti-V. anguillarum immune response by regulating Stat activity negatively to decrease AMP expression in shrimp. PMID:27782165

  11. Family Studies I. Course Objectives, Content Analysis, Supporting Objectives and Content Generalizations.

    ERIC Educational Resources Information Center

    McKenzie, Sharon, Comp.; Martin, Joan, Ed.

    Family Studies I represents the first part of a consumer and homemaking program focusing on individual and family development, parenting, and the daily tasks of living in a family setting. The course is designed to help students study the family as it exists in day-to-day living and to aid them in understanding themselves in relation to their…

  12. Optical sensing of vegetation water content: A synthesis study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetation Water Content (VWC) plays an important role in parameterizing the vegetation influence on microwave soil moisture retrieval. During the past decade, researchers have developed relationships between VWC and vegetation indices available from satellite optical sensors in order to create larg...

  13. Social Studies Content Teaching in Linguistically Diverse Classrooms.

    ERIC Educational Resources Information Center

    Olmedo, Irma M.

    The changing demographics of today's urban schools coupled with the corresponding shortage of bilingual teachers to provide an education for language minority students means that monolingual English teachers will have to carry out content area instruction for students with limited English proficiency (LEP) in the foreseeable future. This paper…

  14. β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.

    PubMed

    Rosanò, Laura; Bagnato, Anna

    2016-07-29

    The advent of targeted therapeutics in human cancer has begun to find novel druggable targets and, in this context, the endothelin-1 receptor (ET-1R), namely ETA receptor (ETAR) and ETB receptor, among the GPCR family represents a class of highly druggable molecules in cancer. ET-1R are aberrantly expressed in human malignancies, potentially representing prognostic factors. Their activation by ligand stimulation initiate signaling cascades activating different downstream effectors, allowing precise control over multiple signaling pathways. ET-1R regulates cell proliferation, survival, motility, cytoskeletal changes, angiogenesis, metastasis as well as drug resistance. The molecular events underlying these responses are the activation of transcriptional factors and coactivators, and downstream genes, acting as key players in tumor growth and progression. ET-1R represent crucial cancer targets that have been exploited for ET-1R therapeutics. Importantly, efforts to explore new information of ETAR in cancer have uncovered that their functions are crucially regulated by multifunctional scaffold protein β-arrestins (β-arrs) which orchestrate the multidimensionality of ETAR signaling into highly regulated and distinct signaling complexes, a property that is highly advantageous for tumor signaling. Moreover, the role of β-arr1 in ET-1 signaling in cancer highlights why the pleiotropic effects of ET-1 and its dynamic signaling are more complex than previously recognized. In order to improve therapeutic strategies that interfere with the widespread effects of ET-1R, it is important to consider antagonists able to turn the receptors "off" selectively controlling β-arr1-dependent signaling, highlighting the possibility that targeting ETAR/β-arr1 may display a large therapeutic window in cancer.

  15. Searching for Educational Content in the For-Profit Internet: Case Study and Analysis.

    ERIC Educational Resources Information Center

    Fabos, Bettina

    This case study investigates the commercialized nature of Internet content and the ways educators and students negotiate and talk about such content. In factoring in the economic and historical context of educational Internet content, this case study also addresses educators' evolving attitudes towards commercialism in the classroom. A survey was…

  16. Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5

    PubMed Central

    Becuwe, Michel; Léon, Sébastien

    2014-01-01

    After endocytosis, membrane proteins can recycle to the cell membrane or be degraded in lysosomes. Cargo ubiquitylation favors their lysosomal targeting and can be regulated by external signals, but the mechanism is ill-defined. Here, we studied the post-endocytic trafficking of Jen1, a yeast monocarboxylate transporter, using microfluidics-assisted live-cell imaging. We show that the ubiquitin ligase Rsp5 and the glucose-regulated arrestin-related trafficking adaptors (ART) protein Rod1, involved in the glucose-induced internalization of Jen1, are also required for the post-endocytic sorting of Jen1 to the yeast lysosome. This new step takes place at the trans-Golgi network (TGN), where Rod1 localizes dynamically upon triggering endocytosis. Indeed, transporter trafficking to the TGN after internalization is required for their degradation. Glucose removal promotes Rod1 relocalization to the cytosol and Jen1 deubiquitylation, allowing transporter recycling when the signal is only transient. Therefore, nutrient availability regulates transporter fate through the localization of the ART/Rsp5 ubiquitylation complex at the TGN. DOI: http://dx.doi.org/10.7554/eLife.03307.001 PMID:25380227

  17. KISS1R signaling promotes invadopodia formation in human breast cancer cell via β-arrestin2/ERK.

    PubMed

    Goertzen, Cameron G; Dragan, Magdalena; Turley, Eva; Babwah, Andy V; Bhattacharya, Moshmi

    2016-03-01

    Kisspeptins (KPs), peptide products of the KISS1 gene are endogenous ligands for the kisspeptin receptor (KISS1R), a G protein-coupled receptor. In numerous cancers, KISS1R signaling plays anti-metastatic roles. However, we have previously shown that in breast cancer cells lacking the estrogen receptor (ERα), kisspeptin-10 stimulates cell migration and invasion by cross-talking with the epidermal growth factor receptor (EGFR), via a β-arrestin-2-dependent mechanism. To further define the mechanisms by which KISS1R stimulates invasion, we determined the effect of down-regulating KISS1R expression in triple negative breast cancer cells. We found that depletion of KISS1R reduced their mesenchymal phenotype and invasiveness. We show for the first time that KISS1R signaling induces invadopodia formation and activation of key invadopodia proteins, cortactin, cofilin and membrane type I matrix metalloproteases (MT1-MMP). Moreover, KISS1R stimulated invadopodia formation occurs via a new pathway involving a β-arrestin2 and ERK1/2-dependent mechanism, independent of Src. Taken together, our findings suggest that targeting the KISS1R signaling axis might be a promising strategy to inhibit invasiveness and metastasis.

  18. Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner.

    PubMed

    Hong, Ling-juan; Jiang, Quan; Long, Sen; Wang, Huan; Zhang, Ling-di; Tian, Yun; Wang, Cheng-kun; Cao, Jing-jing; Tao, Rong-rong; Huang, Ji-yun; Liao, Mei-hua; Lu, Ying-mei; Fukunaga, Kohji; Zhou, Nai-ming; Han, Feng

    2016-03-01

    Valproate exposure is associated with increased risks of autism spectrum disorder. To date, the mechanistic details of disturbance of melatonin receptor subtype 1 (MTNR1A) internalization upon valproate exposure remain elusive. By expressing epitope-tagged receptors (MTNR1A-EGFP) in HEK-293 and Neuro-2a cells, we recorded the dynamic changes of MTNR1A intracellular trafficking after melatonin treatment. Using time-lapse confocal microscopy, we showed in living cells that valproic acid interfered with the internalization kinetics of MTNR1A in the presence of melatonin. This attenuating effect was associated with a decrease in the phosphorylation of PKA (Thr197) and ERK (Thr202/Tyr204). VPA treatment did not alter the whole-cell currents of cells with or without melatonin. Furthermore, fluorescence resonance energy transfer imaging data demonstrated that valproic acid reduced the melatonin-initiated association between YFP-labeled β-arrestin 2 and CFP-labeled MTNR1A. Together, we suggest that valproic acid influences MTNR1A intracellular trafficking and signaling in a β-arrestin 2-dependent manner.

  19. A Case Study of Two Groups of Elementary Prospective Teachers' Experiences in Distinct Mathematics Content Courses

    ERIC Educational Resources Information Center

    Auslander, Susan Swars; Smith, Stephanie Z.; Smith, Marvin E.; Hart, Lynn C.; Carothers, Jody

    2016-01-01

    This multiple case study examined two groups of elementary prospective teachers (n=12) completing distinct mathematics content courses. Data were collected via two belief surveys, one content knowledge assessment, and individual interviews. The findings revealed differences in specialized content knowledge and mathematical beliefs between the two…

  20. Evaluation of the Bilingual Curriculum Content (BCC) Pilot Project: A Three Year Study. Final Report.

    ERIC Educational Resources Information Center

    Rothfarb, Sylvia H.; And Others

    A three-year longitudinal study of bilingual curriculum content (BCC) was initiated in the 1983-84 school year to assess alternative strategies for teaching curriculum content to Limited English Proficient (LEP) students in Dade County (Florida) Public Schools. The BCC strategy (in which content subjects are taught bilingually) was contrasted with…

  1. Content Metadata Standards for Marine Science: A Case Study

    USGS Publications Warehouse

    Riall, Rebecca L.; Marincioni, Fausto; Lightsom, Frances L.

    2004-01-01

    The U.S. Geological Survey developed a content metadata standard to meet the demands of organizing electronic resources in the marine sciences for a broad, heterogeneous audience. These metadata standards are used by the Marine Realms Information Bank project, a Web-based public distributed library of marine science from academic institutions and government agencies. The development and deployment of this metadata standard serve as a model, complete with lessons about mistakes, for the creation of similarly specialized metadata standards for digital libraries.

  2. Multi-Core Processor Memory Contention Benchmark Analysis Case Study

    NASA Technical Reports Server (NTRS)

    Simon, Tyler; McGalliard, James

    2009-01-01

    Multi-core processors dominate current mainframe, server, and high performance computing (HPC) systems. This paper provides synthetic kernel and natural benchmark results from an HPC system at the NASA Goddard Space Flight Center that illustrate the performance impacts of multi-core (dual- and quad-core) vs. single core processor systems. Analysis of processor design, application source code, and synthetic and natural test results all indicate that multi-core processors can suffer from significant memory subsystem contention compared to similar single-core processors.

  3. A study of thematic content in hospital mission statements: a question of values.

    PubMed

    Williams, Jaime; Smythe, William; Hadjistavropoulos, Thomas; Malloy, David C; Martin, Ronald

    2005-01-01

    We examined the content of Canadian hospital mission statements using thematic content analysis. The mission statements that we studied varied in terms of both content and length. Although there was some content related to goals designed to ensure organizational visibility, survival, and competitiveness, the domain of values predominated over our entire coding structure. The primary value-related theme that emerged concerned the importance of patient care.

  4. β-Arrestin1/miR-326 Transcription Unit Is Epigenetically Regulated in Neural Stem Cells Where It Controls Stemness and Growth Arrest

    PubMed Central

    Begalli, Federica; Abballe, Luana; Catanzaro, Giuseppina; Vacca, Alessandra; Napolitano, Maddalena; Tafani, Marco; Giangaspero, Felice; Locatelli, Franco

    2017-01-01

    Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host gene β-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells. Such a regulation is mediated by CpG islands methylation of the common promoter. Epigenetic derepression of β-arrestin1/miR-326 by differentiation signals or demethylating agents leads to suppression of stemness features and cell growth and promotes cell differentiation. β-Arrestin1 inhibits cell proliferation by enhancing the nuclear expression of the cyclin-dependent kinase inhibitor p27. Therefore, we propose a new mechanism for the control of cerebellar NSCs where a coordinated epigenetic mechanism finely regulates β-arrestin1/miR-326 expression and consequently NSCs stemness and cell growth. PMID:28298929

  5. 42 CFR 456.143 - Content of medical care evaluation studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Content of medical care evaluation studies. 456.143...: Medical Care Evaluation Studies § 456.143 Content of medical care evaluation studies. Each medical care evaluation study must— (a) Identify and analyze medical or administrative factors related to the...

  6. 42 CFR 456.243 - Content of medical care evaluation studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Content of medical care evaluation studies. 456.243... Ur Plan: Medical Care Evaluation Studies § 456.243 Content of medical care evaluation studies. Each medical care evaluation study must— (a) Identify and analyze medical or administrative factors related...

  7. Strategic and Organisational Considerations in Planning Content and Language Integrated Learning: A Study on the Coordination between Content and Language Teachers

    ERIC Educational Resources Information Center

    Pavón Vázquez, Víctor; Ávila López, Javier; Gallego Segador, Arturo; Espejo Mohedano, Roberto

    2015-01-01

    Content and language integrated learning (CLIL) is generally recognised as a fruitful example of bilingual education. However, success in CLIL may not be straightforward and may require the establishment of coordination between content and language teachers. The aim of this study is to investigate if content and language teachers are able to plan…

  8. I, Pronoun: A Study of Formality in Online Content

    ERIC Educational Resources Information Center

    Thayer, Alexander; Evans, Mary B.; McBride, Alicia A.; Queen, Matt; Spyridakis, Jan H.

    2010-01-01

    This article presents the results of a study that investigated readers' perceptions of tone formality in online text passages. The study found that readers perceived text passages to be less formal when they contained personal pronouns, active voice verbs, informal punctuation, or verb contractions. The study reveals that professional…

  9. Awakening and Elaborating: Differentiation in Social Studies Content and Instruction.

    ERIC Educational Resources Information Center

    Kaplan, Sandra N.

    2002-01-01

    This article discusses differentiating social studies curricula and instruction for gifted students. It explains the following variables of differentiation: open-ended structure, development and presentation of separate lessons rather than units, the teaching of universal social studies concepts, motivational segments, and use of appropriate…

  10. Content Analysis of Turkish Studies about the Multiple Intelligences Theory

    ERIC Educational Resources Information Center

    Saban, Ahmet

    2009-01-01

    Recently, there has been a significant increase in the number of multiple intelligences (MI) studies in Turkey. Consequently, a systematic analysis of these studies is crucial in order to be able to see the present situation and future trends in the field of education. By this way, it is also hoped that the current analysis will offer an avenue…

  11. ICT Student Teachers' Pedagogical Content Knowledge: A Case Study

    ERIC Educational Resources Information Center

    Yilmaz, Nuray Parlak

    2016-01-01

    This study aimed to identify the difficulties that information technology student teachers have in teaching concepts. This qualitative study was carried out with 12 student teachers. The student teachers were fourth-year students enrolled in the Special Teaching Methods II course in the spring semester of the 2010-2011 academic year. The research…

  12. A Comparative Study of Six Decades of General Science Textbooks: Evaluating the Evolution of Science Content

    ERIC Educational Resources Information Center

    Lewis, Anna

    2008-01-01

    This study examined science textbooks over time to better understand the "science content" expectations that the U.S. educational system deems appropriate for 8th and 9th grade science students. The study attempted to answer the questions: (1) What specific science content has been presented via the textbook from 1952 to 2008? (2) Within…

  13. A National Study of Training Content and Activities for Faculty Development for Online Teaching

    ERIC Educational Resources Information Center

    Meyer, Katrina A.; Murrell, Vicki S.

    2014-01-01

    This article presents the results of a national study of 39 higher education institutions that collected information about their practices for faculty development for online teaching and particularly the content and training activities used during 2011-2012. This study found that the most frequently offered training content (97% of the…

  14. Connecting Content, Context, and Communication in a Sixth-Grade Social Studies Class through Political Cartoons

    ERIC Educational Resources Information Center

    Gallavan, Nancy P.; Webster-Smith, Angela; Dean, Sheila S.

    2012-01-01

    Sixth-grade students are challenged in understanding social studies content relevant to particular contexts, then connecting the content and context to their contemporary lives while communicating new knowledge to peers and teachers. Using political cartoons published after September 11, 2001, one sixth-grade social studies teacher designed…

  15. Preliminary assestment of lint cotton water content in gin-drying temperature studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prior studies to measure total water (free and bound) in lint cotton by Karl Fischer Titration showed the method is more accurate and precise than moisture content by standard oven drying. The objective of the current study was to compare the moisture and total water contents from five cultivars de...

  16. R&D Needs for Assessment in the Content Areas. Testing Study Group: Content Assessment. Report on Research Needs.

    ERIC Educational Resources Information Center

    Aschbacher, Pamela R.; Herman, Joan

    This paper surveys the status of current state and district level practice in content assessment, highlights related research efforts currently underway, and identifies high priority areas for subsequent research in content assessment. A needs assessment for research in content area assessment was conducted during 1986 by the Center for Research…

  17. Studying the information content of TMDs using Monte Carlo generators

    SciTech Connect

    Avakian, H.; Matevosyan, H.; Pasquini, B.; Schweitzer, P.

    2015-02-05

    Theoretical advances in studies of the nucleon structure have been spurred by recent measurements of spin and/or azimuthal asymmetries worldwide. One of the main challenges still remaining is the extraction of the parton distribution functions, generalized to describe transverse momentum and spatial distributions of partons from these observables with no or minimal model dependence. In this topical review we present the latest developments in the field with emphasis on requirements for Monte Carlo event generators, indispensable for studies of the complex 3D nucleon structure, and discuss examples of possible applications.

  18. Integration of Basic Skills into Social Studies Content.

    ERIC Educational Resources Information Center

    Lunstrum, John P.; Irvin, Judith L.

    1981-01-01

    A basic skills model is presented which stresses the skills of writing, reading, study, and research for elementary school pupils. The model focuses on lesson background, the purpose of the reading, independent reading, follow-up discussion, developing related skills, and extending and applying ideas. A lesson about the 1910 British expedition to…

  19. Technical Guide for Implementing Content Standards: Social Studies, June 1999.

    ERIC Educational Resources Information Center

    South Dakota State Dept. of Education and Cultural Affairs, Pierre.

    This technical guide is a resource to help educators implement the adopted social studies standards for South Dakota. The guide to the standards includes the goals, indicators, benchmarks, and grade level standards. It is organized in grade level clusters according to benchmark levels: K-2, 3-5, 6-8, and 9-12. This format is provided as a…

  20. Secondary Social Studies: Arkansas Public School Course Content Guide.

    ERIC Educational Resources Information Center

    Arkansas State Dept. of Education, Little Rock.

    This guide is offered as a framework on which a comprehensive curriculum can be built. Within each subject area and grade level, skills have been identified at three instructional levels: basic, developmental, and extension. The study of political and economic systems, citizenship rights and responsibilities, and the foundations of the U.S.…

  1. A Quantitative Study of High School Yearbook Content.

    ERIC Educational Resources Information Center

    Krepel, Wayne J.; DuVall, Charles R.

    The purpose of this study was to analyze high school yearbooks, relative to quantitative page allotments, when classified by the size of the community, the type of socioeconomic environment of the school, and the size of the graduating class. A normative survey was conducted using a questionnaire requesting the respondent to furnish a copy of the…

  2. Structural and Dynamic Studies of Materials Possessing High Energy Content.

    DTIC Science & Technology

    1980-10-31

    Diazabicyclo[2.2.2] Octene ," N.J. Turro and M.-M Liu H.-D. Martin and M. Kunze, Tetrahedron Lett., 21, 1299 (1980). "Quenching of Chemiexcited Acetone...Derivatives by Electron-Rich and Electron-Poor Ethylenes ," N.J. Turro and G. Farrington, J.Am. Chem. Soc.,102 6051 (1980). "Photoinduced Oxetane Formation...Between 2-Norbornanone and Derivatives with Electron Poor Ethylenes ", N.J. lurro and G. Farrington, J. Am. Chem. Soc., 102, 6056 (1980). "Studies of the

  3. Perspectives: Technology as Content in Social Studies Curricula for Young Learners.

    ERIC Educational Resources Information Center

    Gooler, Dennis D., Ed.

    1995-01-01

    Maintains that elementary social studies teachers who wish to engage students in the social studies must see educational technology as both instructional tools and as content. Concludes that technological literacy will become as important as science or civic literacy. (ACM)

  4. Content-Based Instruction in Primary and Secondary School Settings. Case Studies in TESOL Practice Series

    ERIC Educational Resources Information Center

    Kaufman, Dorit, Ed.; Crandall, JoAnn, Ed.

    2005-01-01

    Content-based instruction (CBI) challenges English language educators to teach English using materials that learners encounter in their regular subject-area classes. This volume helps ESL and EFL teachers meet that challenge by providing them with creative ways to integrate English language learning with the content that students study at primary…

  5. New Histories for a New State: A Study of History Textbook Content in Northern Ireland

    ERIC Educational Resources Information Center

    Terra, Luke

    2014-01-01

    This study examined the changing content of history textbooks in Northern Ireland, drawing on a sample of 15 textbooks published from 1968 to 2010. Findings from the content and narrative analysis indicated that following the introduction of the Northern Ireland Curriculum in 1991, history textbooks shifted from a narrative to source-driven…

  6. Evaluation of the Use of Team Teaching for Delivering Sensitive Content: A Pilot Study

    ERIC Educational Resources Information Center

    Kerridge, Joanna; Kyle, Gaye; Marks-Maran, Diane

    2009-01-01

    Many programmes in further and higher education contain sensitive areas of content, such as diversity, racism, power and privilege, breaking bad news, counselling, sex education and ethical decision making. Team teaching may be a useful method for delivering sensitive areas of course content. This article presents a pilot study that was undertaken…

  7. Every Day Successes: Powerful Integration of Social Studies Content and English-Language Arts

    ERIC Educational Resources Information Center

    Field, Sherry L.; Bauml, Michelle; Ledbetter, Mary

    2011-01-01

    Instructional time for social studies has been reduced nationwide, particularly in the elementary grades. Yet states continue to promote content standards in history, economics, civics, and geography for young learners. Purposeful integrative content that is appropriate for grades K-6, while sometimes difficult to find, seems to many elementary…

  8. A Trend Study of Advertising Content Used by Banks Before, During and After a Banking Collapse.

    ERIC Educational Resources Information Center

    De Riemer, Cynthia; Baxter, Richard L.

    To examine the content of newspaper advertisements used by banks before, during, and after a major bank collapse, issues of the Knoxville (Tennessee) "News Sentinel" from 1982, 1983, and 1984 were analyzed for bank sponsored product and nonproduct advertisements. These advertisements were studied for type, size, and content relating to…

  9. Synergistic regulation of m2 muscarinic acetylcholine receptor desensitization and sequestration by G protein-coupled receptor kinase-2 and beta-arrestin-1.

    PubMed

    Schlador, M L; Nathanson, N M

    1997-07-25

    The m2 muscarinic acetylcholine receptor (m2 mAChR) belongs to the superfamily of G protein-coupled receptors and is regulated by many processes that attenuate signaling following prolonged stimulation by agonist. We used a heterologous expression system to examine the ability of G protein-coupled receptor kinase-2 (GRK2) and beta-arrestin-1 to regulate the phosphorylation state and to promote desensitization and sequestration of the m2 mAChR. Treatment of JEG-3 cells transiently expressing the m2 mAChR with a muscarinic agonist induced an approximately 4- or 8-fold increase in receptor phosphorylation in the absence or presence of cotransfected GRK2, respectively, compared with untreated cells transfected with receptor alone. Using the expression of a cAMP-regulated reporter gene to measure receptor function, we found that transiently transfected m2 mAChRs underwent functional desensitization following exposure to agonist. Transfected GRK2 enhanced agonist-induced functional desensitization in a manner that was synergistically enhanced by cotransfection of beta-arrestin-1, which had no effect on m2 mAChR function when coexpressed in the absence of GRK2. Finally, GRK2 and beta-arrestin-1 synergistically enhanced both the rate and extent of agonist-induced m2 mAChR sequestration. These results are the first to demonstrate that agonist-induced desensitization and sequestration of the m2 mAChR in the intact cell can be enhanced by the presence of GRK2 and beta-arrestin-1 and show that these molecules have multiple actions on the m2 mAChR.

  10. Teachers' Professional Development: A Content Analysis about the Tendencies in Studies

    ERIC Educational Resources Information Center

    Yurtseven, Nihal; Bademcioglu, Mehtap

    2016-01-01

    The purpose of this study is to carry out a content analysis about the studies on teachers' professional development and to determine the tendencies in these studies. Within this scope, 60 studies that were registered to Turkish National Thesis Centre and ProQuest database between the years 2005-2015 were examined. Of the 60 studies, 37 of them…

  11. Studying protein-reconstituted proteoliposome fusion with content indicators in vitro

    PubMed Central

    Diao, Jiajie; Zhao, Minglei; Zhang, Yunxiang; Kyoung, Minjoung; Brunger, Axel T.

    2015-01-01

    In vitro reconstitution assays are commonly used to study biological membrane fusion. However, to date, most ensemble and single-vesicle experiments involving SNARE proteins have been performed only with lipid-mixing, but not content-mixing indicators. Through simultaneous detection of lipid and small content-mixing indicators, we found that lipid mixing often occurs seconds prior to content mixing, or without any content mixing at all, during a 50-sec observation period, for Ca2+-triggered fusion with SNAREs, full-length synaptotagmin-1, and complexin. Our results illustrate the caveats of commonly used bulk lipid-mixing fusion experiments. We recommend that proteoliposome fusion experiments should always employ content-mixing indicators in addition to, or in place of, lipid-mixing indicators. PMID:23625805

  12. 78 FR 42085 - Draft Guidance for Industry on Pediatric Study Plans: Content of and Process for Submitting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ...: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Pediatric Study Plans... Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Pediatric Study... draft guidance for industry entitled ``Pediatric Study Plans: Content of and Process for...

  13. A study of the metal content of municipal solid waste. Final report

    SciTech Connect

    Churney, K.L.; Domalski, E.S.

    1998-01-01

    Knowledge of the content of toxic components, so called pollutant precursors, in the municipal solid waste (MSW) stream is essential to development of the strategies for source reduction and reuse, recycling, composting and disposal. Data are scarce; trends in composition for any locality even more so. In a previous study the total and water soluble chlorine content of the components of municipal solid waste were determined from sampling studies at two sites, Baltimore County, MD, and Brooklyn, NY, each for a five day period. The total sulfur content of the combined combustible components was also determined. Because of the scarcity of data and synergistic effects, it seemed appropriate to determine the heavy metal content of the preceding material prior to its disposal. The metals chosen were the so-called priority pollutant metals (PPM): antimony, arsenic, beryllium, cadmium, chromium, copper, lead, mercury, nickel, selenium, silver, thallium, and zinc.

  14. Feasibility study for the quantification of total protein content by multiple prompt gamma-ray analysis.

    PubMed

    Toh, Y; Murakami, Y; Furutaka, K; Kimura, A; Koizumi, M; Hara, K; Kin, T; Nakamura, S; Harada, H

    2012-06-01

    Protein is an important nutrient in foods. The classical nitrogen analysis method is the Kjeldahl technique, which is time-consuming and inconvenient. As a convenient method to quantify protein content in biological samples, the feasibility of application of multiple prompt gamma-ray analysis (MPGA) to the quantification was studied. Results for protein content are reported for several reference materials and prove the method to be reliable.

  15. The Relationship Between Sexual Content on Mass Media and Social Media: A Longitudinal Study.

    PubMed

    Vandenbosch, Laura; van Oosten, Johanna M F; Peter, Jochen

    2015-12-01

    The goal of this study was to investigate whether exposure to sexual reality television content and Internet pornography (IP) is related to sexual self-presentation on social media. Based on a two-wave panel survey among 1,765 adolescents aged 13-17 years, we found that watching sexual reality television content stimulated adolescents to produce and distribute sexual images of themselves on social media. In turn, sexual self-presentation on social media led adolescents to watch sexual reality television content more frequently. These relationships were similar among boys and girls. No reciprocal relationship between exposure to IP and boys' and girls' sexual self-presentation on social media was found. The results suggest that sexual content in mainstream mass media may predict adolescents' sexually oriented behavior on social media and vice versa. Moreover, adolescents seem to differentiate between types of sexual content (i.e., mainstream versus more explicit sexual content) when incorporating sexual media content in their sexual behavior online.

  16. Mitochondrial DNA content contributes to healthy aging in Chinese: a study from nonagenarians and centenarians.

    PubMed

    He, Yong-Han; Lu, Xiang; Wu, Huan; Cai, Wang-Wei; Yang, Li-Qin; Xu, Liang-You; Sun, Hong-Peng; Kong, Qing-Peng

    2014-07-01

    Mitochondrial DNA (mtDNA) content plays an important role in energy production and sustaining normal physiological function. A decline in the mtDNA content and subsequent dysfunction cause various senile diseases, with decreasing mtDNA content observed in the elderly individuals with age-related diseases. In contrast, the oldest old individuals, for example, centenarians, have a delayed or reduced prevalence of these diseases, suggesting centenarians may have a different pattern of the mtDNA content, enabling them to keep normal mitochondrial functions to help delay or escape senile diseases. To test this hypothesis, a total of 961 subjects, consisting of 424 longevity subjects and 537 younger control subjects from Hainan and Sichuan provinces of China, were recruited for this study. The mtDNA content was found to be inversely associated with age among the age of group 40-70 years. Surprisingly, no reduction of mtDNA content was observed in nonagenarians and centenarians; instead, these oldest old showed a significant increase than the elderly people aged between 50 and 70 years. The results suggest the higher mtDNA content may convey a beneficial effect to the longevity of people through assuring sufficient energy supply.

  17. Preliminary study: fibre content in pet rabbit diets, crude fibre versus total dietary fibre.

    PubMed

    Molina, J; Martorell, J; Hervera, M; Pérez-Accino, J; Fragua, V; Villaverde, C

    2015-04-01

    Fibre is an important nutrient for rabbit health, and, on commercial pet rabbit packaging, it is labelled as crude fibre (CF). In several species, it is considered that CF is not an accurate representation of the fibre content in feedstuffs. The objective of this study was to compare the CF stated on the label (CFL) with laboratory analysis of CF (CFA) and the analysed content of total dietary fibre (TDF) in different commercial pet rabbit feeds. We selected 15 commercial diets and analysed CF and TDF. A mixed model was used to evaluate differences between CFL, CFA and TDF, and linear regression was performed to study the correlation between CFL and CFA with TDF. CFA and CFL were not significantly different (p = 0.836) in the feeds studied, and both were lower than TDF (p < 0.001). The correlations between TDF and both CFA and CFL were significant (p < 0.001 and p = 0.02, respectively), but the correlation was better with CFA (R = 0.86) than with CFL (R = 0.53). As expected, TDF content was higher than CF content, an average of two times. These results suggest that the CF content in rabbit diets reported on the label is not an appropriate indicator of their total fibre content, although further work with a larger sample size is required to confirm these results.

  18. Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis.

    PubMed

    Wang, W-Y; Wu, X-M; Jia, L-J; Zhang, H-H; Cai, F; Mao, H; Xu, W-C; Chen, L; Zhang, J; Hu, S-F

    2016-01-28

    Beta-arrestins (β-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that β-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. In the present study, we showed that activation of mGluR7 with a group III mGluRs orthosteric agonist LAP4 or an atypical mGluR7 allosteric agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) significantly attenuated sevoflurane-induced neuronal apoptosis. Interestingly, this neuroprotective role of LAP4 could be partially reduced by β-arr1 small interfering RNA (siRNA) or β-arr2 siRNA transfection. In contrast, β-arr2 siRNA transfection alone abolished the effects of AMN082 on sevoflurane neurotoxicity. In addition, administration of LAP4 or AMN082 significantly enhanced Phospho-ERK1/2 in sevoflurane neurotoxicity, which could be abrogated by β-arr2 siRNA transfection, but not by β-arr1 siRNA transfection. Increased β-arr2-dependent Phospho-ERK1/2 signaling alleviated sevoflurane neurotoxicity by inhibiting bad phosphorylation. We also found that the neuroprotective role of AMN082 was completely reversed by ERK1/2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126). Alternatively, treatment with U0126 partially suppressed the neuroprotective of LAP4, suggesting that other mechanisms may be implicated in this process. Further investigation indicated that, in the scenario of sevoflurane neurotoxicity, application of LAP4 (but not AMN082) increased the interaction of β-arrs with transcriptional factors CREB binding protein (CBP) and p300. LAP4 also enhanced the β-arr1-dependent H3 and H4 acetylation in

  19. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    SciTech Connect

    Mingshi Wang; Dangyu Song; Baoshan Zheng; R.B. Finkelman

    2008-10-15

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong.

  20. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    USGS Publications Warehouse

    Wang, M.; Song, D.; Zheng, B.; Finkelman, R.B.; ,

    2008-01-01

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong. ?? 2008 New York Academy of Sciences.

  1. G protein-coupled receptor kinase 6/β-arrestin 2 system in a rat model of dopamine supersensitivity psychosis.

    PubMed

    Oda, Yasunori; Tadokoro, Shigenori; Takase, Masayuki; Kanahara, Nobuhisa; Watanabe, Hiroyuki; Shirayama, Yukihiko; Hashimoto, Kenji; Iyo, Masaomi

    2015-12-01

    In humans, long-term antipsychotic treatment is known to induce movement disorders and a psychosis, called dopamine supersensitivity psychosis (DSP). The mechanism by which chronic administration of antipsychotic(s) causes DSP may be the treatment-induced up-regulation of dopamine D2 receptors (DRD2). G protein-coupled receptor kinase 6 (GRK6) and beta-arrestin 2 (ARRB2) play important roles in the trafficking of DRD2 by phosphorylation and internalization. We investigated the effects of chronic continuous treatment with mini-pump-administered haloperidol (HAL) on the sensitivity of Wistar rats to dopamine, as measured by the locomotor response to methamphetamine (MAP) and the density of striatal DRD2. Chronic continuous treatment with HAL resulted in significantly higher locomotor response to MAP and significantly higher striatal DRD2 density compared with those in rats administered vehicle (VEH). Enzyme-linked immunosorbent assays revealed that striatal ARRB2 in DSP model rats tended to decrease in comparison with that in the VEH group. In addition, the ratio of GRK6/ARRB2 in DSP model rats was significantly higher than that in controls. Our results suggest that alterations of the GRK6 and ARRB2 system could induce both DRD2 up-regulation and impairment of the dopamine signaling pathway, resulting potentially in the development of DSP.

  2. Muscarinic Acetylcholine Receptor M3 Modulates Odorant Receptor Activity via Inhibition of β-Arrestin-2 Recruitment

    PubMed Central

    Jiang, Yue; Li, Yun Rose; Tian, Huikai; Ma, Minghong; Matsunami, Hiroaki

    2015-01-01

    The olfactory system in rodents serves a critical function in social, reproductive, and survival behaviors. Processing of chemosensory signals in the brain is dynamically regulated in part by an animal's physiological state. We previously reported that type 3 muscarinic acetylcholine receptors (M3-Rs) physically interact with odorant receptors (ORs) to promote odor-induced responses in a heterologous expression system. However, it is not known how M3-Rs affect the ability of olfactory sensory neurons (OSNs) to respond to odors. Here, we show that an M3-R antagonist attenuates odor-induced responses in OSNs from wild-type, but not M3-R-null mice. Using a novel molecular assay, we demonstrate that the activation of M3-Rs inhibits the recruitment of β-arrestin-2 to ORs, resulting in a potentiation of odor-induced response in OSNs. These results suggest a role for acetylcholine in modulating olfactory processing at the initial stages of signal transduction in the olfactory system. PMID:25800153

  3. Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).

    PubMed

    Qi, Shiqian; O'Hayre, Morgan; Gutkind, J Silvio; Hurley, James H

    2014-02-21

    After protracted stimulation, the β2-adrenergic receptor and many other G-protein-coupled receptors are ubiquitinated and down-regulated. Arrestin-related domain-containing protein-3 (ARRDC3) has been proposed to recruit the ubiquitin ligase Nedd4 to the β2-adrenergic receptor. ARRDC3 contains two PPXY motifs that could potentially interact with any of the four WW domains of Nedd4. Here we dissect the interaction determinants. ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1 and 1.7 Å resolution. The structures revealed conformational changes upon binding and the hydrogen bonding network in exquisite detail. Tight packing of ARRDC3 Val-352', part of a 310 helix at the C terminus of PPXY1, is important for high affinity binding to WW3. Although no single WW domain is strictly essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations, with Kd values as low as 300 nM.

  4. Recruitment of β-Arrestin 1 and 2 to the β2-Adrenoceptor: Analysis of 65 Ligands

    PubMed Central

    Littmann, Timo; Göttle, Martin; Reinartz, Michael T.; Kälble, Solveig; Wainer, Irving W.; Ozawa, Takeaki

    2015-01-01

    Beyond canonical signaling via Gαs and cAMP, the concept of functional selectivity at β2-adrenoceptors (β2ARs) describes the ability of adrenergic drugs to stabilize ligand-specific receptor conformations to initiate further signaling cascades comprising additional G-protein classes or β-arrestins (βarr). A set of 65 adrenergic ligands including 40 agonists and 25 antagonists in either racemic or enantiopure forms was used for βarr recruitment experiments based on a split-luciferase assay in a cellular system expressing β2AR. Many agonists showed only (weak) partial agonism regarding βarr recruitment. Potencies and/or efficacies increased depending on the number of chirality centers in (R) configuration; no (S)-configured distomer was more effective at inducing βarr recruitment other than the eutomer. βarr2 was recruited more effectively than βarr1. The analysis of antagonists revealed no significant effects on βarr recruitment. Several agonists showed preference for activation of Gαs GTPase relative to βarr recruitment, and no βarr-biased ligand was identified. In conclusion: 1) agonists show strong bias for Gαs activation relative to βarr recruitment; 2) agonists recruit βarr1 and βarr2 with subtle differences; and 3) there is no evidence for βarr recruitment by antagonists. PMID:26306764

  5. Is Pedagogical Content Knowledge (PCK) Necessary for Reformed Science Teaching?: Evidence from an Empirical Study

    ERIC Educational Resources Information Center

    Park, Soonhye; Jang, Jeong-Yoon; Chen, Ying-Chih; Jung, Jinhong

    2011-01-01

    This study tested a hypothesis that focused on whether or not teachers' pedagogical content knowledge (PCK) is a necessary body of knowledge for reformed science teaching. This study utilized a quantitative research method to investigate the correlation between a teacher's PCK level as measured by the PCK rubric (Park et al. 2008) and the degree…

  6. Comparative Study of Teaching Content in Teacher Education Programmes in Canada, Denmark, Finland and Singapore

    ERIC Educational Resources Information Center

    Rasmussen, Jens; Bayer, Martin

    2014-01-01

    This article presents the results of a comparative study of the content in selected teacher education programmes for primary and lower secondary teachers in Canada, Denmark, Finland and Singapore. First and foremost, the study is a comparison between teacher education programmes in, on the one hand, Canada, Finland and Singapore, all of which…

  7. The Six Remaining Facts: Social Studies Content Knowledge and Elementary Preservice Teachers

    ERIC Educational Resources Information Center

    Sanchez, Rebecca M.

    2010-01-01

    This article explores and examines the social studies content knowledge that preservice teachers have about commonly studies historical figures. The data indicate that preservice teachers often have shallow and decontextualized understandings of historical individuals such as Christopher Columbus and Helen Keller, despite their being repeatedly…

  8. Implementation of a Text-Based Content Intervention in Secondary Social Studies Classes

    ERIC Educational Resources Information Center

    Wanzek, Jeanne; Vaughn, Sharon

    2016-01-01

    We describe teacher fidelity (adherence to the components of the treatment as specified by the research team) based on a series of studies of a multicomponent intervention, Promoting Acceleration of Comprehension and Content Through Text (PACT), with middle and high school social studies teachers and their students. Findings reveal that even with…

  9. Singapore Pre-Service Secondary Mathematics Teachers' Content Knowledge: Findings from an International Comparative Study

    ERIC Educational Resources Information Center

    Toh, Tin Lam; Kaur, Berinderjeet; Koay, Phong Lee

    2013-01-01

    In this article, we explore the mathematical content knowledge of one entire cohort of pre-service teachers (N = 107) through analysing their performance in a Secondary Mathematics Audit that was developed for the International Comparative Studies in Mathematics Teacher Training that was initiated by the University of Plymouth. We study how their…

  10. Promoting Acceleration of Comprehension and Content through Text in High School Social Studies Classes

    ERIC Educational Resources Information Center

    Wanzek, Jeanne; Swanson, Elizabeth A.; Roberts, Greg; Vaughn, Sharon; Kent, Shawn C.

    2015-01-01

    The purpose of this study was to evaluate the efficacy of Promoting Acceleration of Comprehension and Content Through Text intervention implemented with 11th-grade students enrolled in U.S. History classes. Using a within-teacher randomized design, the study was conducted in 41 classes (23 treatment classes) with 14 teachers providing the…

  11. The Content of Electronic Mentoring: A Study of Special Educators Participating in an Online Mentoring Program

    ERIC Educational Resources Information Center

    Gentry, Roberta

    2011-01-01

    The purpose of this study was to describe the content and frequency of interactions that occurred in an electronic mentoring program involving beginning special educators and their mentors. In addition, the characteristics of mentors' and mentees' and perceived outcomes of mentees' were provided. This study sought to address questions about the…

  12. A Study to Determine the Impact of Professional Development on Teachers' Knowledge of Literacy Content

    ERIC Educational Resources Information Center

    Bradley, Rosaline Teresita

    2012-01-01

    Scope and Method of Study: This quantitative study investigated the impact of professional development on Belizean teachers' knowledge of literacy content needed to effectively develop early literacy skills of primary school children between the ages of five to eight. The specific focus of the research was to survey teachers' knowledge level…

  13. Seven Principles of Instructional Content Design for a Remote Laboratory: A Case Study on ERRL

    ERIC Educational Resources Information Center

    Cagiltay, N. E.; Aydin, E.; Aydin, C. C.; Kara, A.; Alexandru, M.

    2011-01-01

    This paper discusses the results of a study of the requirements for developing a remote radio frequency (RF) laboratory for electrical engineering students. It investigates students' preferred usage of the technical content of a state-of-the-art RF laboratory. The results of this study are compared to previous findings, which dealt with other user…

  14. Links between Content Knowledge and Practice in a Mathematics Teacher Education Course: A Case Study

    ERIC Educational Resources Information Center

    Brijlall, D.; Isaac, V.

    2011-01-01

    This qualitative study examined the link between content knowledge and classroom practice from the perceptions of two university lecturers. The study was contextualized at a higher education institution in South Africa where the two university lecturers were lecturing to a second year undergraduate teacher trainee class (n = 78). The research was…

  15. Content Analysis of Primary and Secondary School Textbooks Regarding Malaria Control: A Multi-Country Study

    PubMed Central

    Nonaka, Daisuke; Jimba, Masamine; Mizoue, Tetsuya; Kobayashi, Jun; Yasuoka, Junko; Ayi, Irene; Jayatilleke, Achini C.; Shrestha, Sabina; Kikuchi, Kimiyo; Haque, Syed E.; Yi, Siyan

    2012-01-01

    Background In tropical settings, malaria education at school is potentially useful, but textbook content related to malaria education has so far received little attention. This study aimed to examine whether school textbooks contain sufficient knowledge and skills to help children in primary and lower secondary schools and their family members to cope with malaria. Methodology/Principal Findings This was a descriptive, cross-country study. We collected textbooks that were used by children in grades one to nine from nine countries endemic for malaria: Laos, Cambodia, Nepal, Bangladesh, Sri Lanka, Zambia, Niger, Benin, and Ghana. Two reviewers per country identified descriptions about malaria by seeking the term “malaria” or a local word that corresponds to malaria in languages other than English. The authors categorized the identified descriptions according to the content of the descriptions. Additionally, the authors examined whether the identified contents addressed life skill messages. Of a total of 474 textbooks collected, 35 contained descriptions about malaria. The most commonly included content was transmission mode/vector (77.1%), followed by preventive measures (60.0%), epidemiology (57.1%), cause/agent (54.3%), signs/symptoms (37.1%) and treatment (22.9%). Treatment-related content was not included in any textbooks from four countries and textbooks failed to recommend the use of insecticide-treated bed nets in five countries. Very few textbooks included content that facilitated prompt treatment, protection of risk groups, and use of recommended therapy. Conclusion/Significance Textbooks rarely included knowledge and skills that are crucial to protect schoolchildren and their families from malaria. This study identified the need for improvement to textbook contents regarding malaria. PMID:22574203

  16. Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

    PubMed

    Coletta, Marina; Gates, Fred K; Marciani, Luca; Shiwani, Henna; Major, Giles; Hoad, Caroline L; Chaddock, Gemma; Gowland, Penny A; Spiller, Robin C

    2016-01-14

    Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

  17. Consumers’ estimation of calorie content at fast food restaurants: cross sectional observational study

    PubMed Central

    Condon, Suzanne K; Kleinman, Ken; Mullen, Jewel; Linakis, Stephanie; Rifas-Shiman, Sheryl; Gillman, Matthew W

    2013-01-01

    Objective To investigate estimation of calorie (energy) content of meals from fast food restaurants in adults, adolescents, and school age children. Design Cross sectional study of repeated visits to fast food restaurant chains. Setting 89 fast food restaurants in four cities in New England, United States: McDonald’s, Burger King, Subway, Wendy’s, KFC, Dunkin’ Donuts. Participants 1877 adults and 330 school age children visiting restaurants at dinnertime (evening meal) in 2010 and 2011; 1178 adolescents visiting restaurants after school or at lunchtime in 2010 and 2011. Main outcome measure Estimated calorie content of purchased meals. Results Among adults, adolescents, and school age children, the mean actual calorie content of meals was 836 calories (SD 465), 756 calories (SD 455), and 733 calories (SD 359), respectively. A calorie is equivalent to 4.18 kJ. Compared with the actual figures, participants underestimated calorie content by means of 175 calories (95% confidence interval 145 to 205), 259 calories (227 to 291), and 175 calories (108 to 242), respectively. In multivariable linear regression models, underestimation of calorie content increased substantially as the actual meal calorie content increased. Adults and adolescents eating at Subway estimated 20% and 25% lower calorie content than McDonald’s diners (relative change 0.80, 95% confidence interval 0.66 to 0.96; 0.75, 0.57 to 0.99). Conclusions People eating at fast food restaurants underestimate the calorie content of meals, especially large meals. Education of consumers through calorie menu labeling and other outreach efforts might reduce the large degree of underestimation. PMID:23704170

  18. Implementation of a Text-Based Content Intervention in Secondary Social Studies Classes.

    PubMed

    Wanzek, Jeanne; Vaughn, Sharon

    2016-12-01

    We describe teacher fidelity (adherence to the components of the treatment as specified by the research team) based on a series of studies of a multicomponent intervention, Promoting Acceleration of Comprehension and Content Through Text (PACT), with middle and high school social studies teachers and their students. Findings reveal that even with highly specified materials and implementing practices that are aligned with effective reading comprehension and content instruction, teachers' fidelity was consistently low for some components and high for others. Teachers demonstrated consistently high implementation fidelity and quality for the instructional components of building background knowledge (comprehension canopy) and teaching key content vocabulary (essential words), whereas we recorded consistently lower fidelity and quality of implementation for the instructional components of critical reading and knowledge application.

  19. A comparative study of six decades of general science textbooks: Evaluating the evolution of science content

    NASA Astrophysics Data System (ADS)

    Lewis, Anna

    This study examined science textbooks over time to better understand the science content expectations that the U.S. educational system deems appropriate for 8th and 9th grade science students. The study attempted to answer the questions: (1) What specific science content has been presented via the textbook from 1952 to 2008? (2) Within which areas and in what way does the science content change? (3) Are new scientific findings reflected in 8th and 9th grade U.S. general science textbooks? Twenty-six themes were identified which reflect five areas in science: Chemistry, Physics, Earth Science, Biology, and Process of Science. Trends in science content in U.S. 8th and 9th grade general science textbooks, as revealed by this data sample, indicated no statistically significant change in depth of coverage in Physics and Process of Science over the past 60 years, no significant change in depth of coverage in Earth Science and Biology in the last 40 years, and no significant change in coverage in Chemistry over the last 30 years. Additionally, a total of sixteen new discoveries were found in the textbook sample. For classroom teachers this information may alert them to the necessity of going beyond the textbook in preparing students for life in a global society. In educational practice, this research supports and reinforces the need for inquiry learning and socioscientific curricula. It may also influence educators to challenge assumptions regarding the value and selection of the traditional classic science content.

  20. Systematic Study of the Content of Phytochemicals in Fresh and Fresh-Cut Vegetables

    PubMed Central

    Alarcón-Flores, María Isabel; Romero-González, Roberto; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2015-01-01

    Vegetables and fruits have beneficial properties for human health, because of the presence of phytochemicals, but their concentration can fluctuate throughout the year. A systematic study of the phytochemical content in tomato, eggplant, carrot, broccoli and grape (fresh and fresh-cut) has been performed at different seasons, using liquid chromatography coupled to triple quadrupole mass spectrometry. It was observed that phenolic acids (the predominant group in carrot, eggplant and tomato) were found at higher concentrations in fresh carrot than in fresh-cut carrot. However, in the case of eggplant, they were detected at a higher content in fresh-cut than in fresh samples. Regarding tomato, the differences in the content of phenolic acids between fresh and fresh-cut were lower than in other matrices, except in winter sampling, where this family was detected at the highest concentration in fresh tomato. In grape, the flavonols content (predominant group) was higher in fresh grape than in fresh-cut during all samplings. The content of glucosinolates was lower in fresh-cut broccoli than in fresh samples in winter and spring sampling, although this trend changes in summer and autumn. In summary, phytochemical concentration did show significant differences during one-year monitoring, and the families of phytochemicals presented different behaviors depending on the matrix studied. PMID:26783709

  1. Socialization Content in Schools and Education for Sustainable Development--I. A Study of Teachers' Selective Traditions

    ERIC Educational Resources Information Center

    Sund, Per; Wickman, Per-Olof

    2011-01-01

    This article studies content issues by examining teachers' communicated socialization content. The value-laden socialization content constitutes the educational context for the teaching of integrated subject matter and has not yet been thoroughly studied empirically in environmental education research. The implications of the results can be…

  2. Analysis of Pedagogical Content Knowledge Studies in the Context of Mathematics Education in Turkey: A Meta-Synthesis Study

    ERIC Educational Resources Information Center

    Simsek, Nurullah; Boz, Nihat

    2016-01-01

    Studies that explore pedagogical content knowledge (PCK) in the field of mathematics education date back to the turn of the century in Turkey. In recent years, studies on PCK have gained momentum. Master's theses and doctoral dissertations have been written on PCK. In this context, there is a need to analyze the studies on PCK in Turkey to…

  3. Content Analysis of Meta-Analytic Studies from I/O Psychology.

    ERIC Educational Resources Information Center

    Cornwell, John M.

    The use of meta-analysis in industrial and organizational psychology has become quite common. Unfortunately, the understanding and research necessary to ensure appropriate application of the technique have not been as widespread. As part of a larger study, a content analysis of meta-analyses from the industrial and organizational psychological…

  4. The Structure of Mixed Method Studies in Educational Research: A Content Analysis

    ERIC Educational Resources Information Center

    Bryant, Lauren H.

    2011-01-01

    Educational researchers are beginning to use mixed methods designs to answer complex research questions. This content analysis investigates the structure and use of mixed methods in educational research in order to work toward a more standardized presentation. I used a concurrent mixed methods approach to analyze 30 studies from three prominent…

  5. Programme Content Orientation in Vocational Education and Training and Life Chances--A Comparative Study

    ERIC Educational Resources Information Center

    Kap, Hrvoje

    2014-01-01

    Comparative studies of vocational education and training systems rarely conduct systematic comparisons of the content of educational programmes, partly because of methodological difficulties. Yet, comparing the organisation of curricula can increase our understanding of how programme design reflects orientation towards various life chances in…

  6. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our aim in carrying out this analysis, was to assess the predictive value of plasma phosphatidylcholine (PC) DHA content, DHA intake, and fish intake for the risk of developing dementia in the Framingham Heart Study. A cohort of 899 subjects free of dementia was followed to assess the onset of incid...

  7. A Study of the Structure and Content of Principal Selection Interviews in Pennsylvania

    ERIC Educational Resources Information Center

    Weber, Elizabeth A.

    2012-01-01

    The principal plays a key role in student success. The employment interview is a critical element in the principal selection process. This study examined the interview structure and the content of the interview questions that districts used in their principal search for the 2011-2012 school year. The research-based practices for interview…

  8. Teaching Science with Technology: Case Studies of Science Teachers' Development of Technology, Pedagogy, and Content Knowledge

    ERIC Educational Resources Information Center

    Guzey, S. Selcen; Roehrig, Gillian H.

    2009-01-01

    This study examines the development of technology, pedagogy, and content knowledge (TPACK) in four in-service secondary science teachers as they participated in a professional development program focusing on technology integration into K-12 classrooms to support science as inquiry teaching. In the program, probeware, mind-mapping tools (CMaps),…

  9. Developing Pedagogical Technology Integration Content Knowledge in Preservice Teachers: A Case Study Approach

    ERIC Educational Resources Information Center

    Brantley-Dias, Laurie; Kinuthia, Wanjira; Shoffner, Mary B.; de Castro, Christopher; Rigole, Neil J.

    2007-01-01

    This research examined the effects of case-based instructional strategies on the development of Pedagogical Technology Integration Content Knowledge (PTICK) in alternative teacher preparation students. The study was part of the Crossroads Project funded by the Preparing Tomorrow's Teachers for Using Technology (PT3) grant from the United States…

  10. Developing Storypath Units for Integrating Social Studies and the Michigan Content Standards.

    ERIC Educational Resources Information Center

    Scott, Renay

    2000-01-01

    Describes "Storypath," a lesson plan framework that integrates social studies curriculum with the basic elements of a story. Outlines a three-week history unit, "The Coming of the American Revolution," created with "Storypath." Discusses the correlation between Storypath and the Michigan content standards and…

  11. Family Peer Advocates: A Pilot Study of the Content and Process of Service Provision

    ERIC Educational Resources Information Center

    Wisdom, Jennifer P.; Olin, Serene; Shorter, Priscilla; Burton, Geraldine; Hoagwood, Kimberly

    2011-01-01

    Professional family peer advocates are increasingly employed by public mental health systems to deliver family-to-family support that reduces barriers families face in accessing children's mental health care. These services, however, are neither uniformly available nor standardized. This pilot study describes the process, content and context of…

  12. Technology-Based Content through Virtual and Physical Modeling: A National Research Study

    ERIC Educational Resources Information Center

    Ernst, Jeremy V.; Clark, Aaron C.

    2009-01-01

    Visualization is becoming more prevalent as an application in science, engineering, and technology related professions. The analysis of static and dynamic graphical visualization provides data solutions and understandings that go beyond traditional forms of communication. The study of technology-based content and the application of conceptual…

  13. Studying the News on Public Health: How Content Analysis Supports Media Advocacy

    ERIC Educational Resources Information Center

    Dorfman, Lori

    2003-01-01

    Objective: To describe how content analysis of the news assists media advocates. Methods: A description of how findings from the Berkeley Media Studies Group's research on how 2 public health issues have been portrayed in the news has informed media advocacy. Results: For media advocates, the research suggests they make themselves available to…

  14. Temporal stability of soil water contents as affected by weather patterns: a simulation study.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Temporal stability of soil water content (TS SWC) is a natural phenomenon that recently attracts attention and finds multiple applications. Large variations in the interannual and interseasonal TS SWC have been encountered among locations studied by various authors. The objective of this work was ...

  15. A Content Study of Selected American Newspapers on the Fall of China in 1949.

    ERIC Educational Resources Information Center

    Chao, Edward Yi

    A study examined the treatment of Chinese affairs in four American newspapers during December 1949, when China fell to Communism. Content analyses were conducted on issues of the "New York Times,""The Christian Science Monitor,""The Chicago Tribune," and "The St. Louis Post-Dispatch." Each of the 416…

  16. Developing Fair Tests for Mathematics Curriculum Comparison Studies: The Role of Content Analyses

    ERIC Educational Resources Information Center

    Chavez, Oscar; Papick, Ira; Ross, Daniel J.; Grouws, Douglas A.

    2011-01-01

    This article describes the process of development of assessment instruments for a three-year longitudinal comparative study that focused on evaluating American high school students' mathematics learning from two distinct approaches to content organization: curriculum built around a sequence of three full-year courses (Algebra 1, Geometry, and…

  17. A Content Validity Study of the Children's Version of The Family Environment Scale.

    ERIC Educational Resources Information Center

    Pino, Christopher J.

    1985-01-01

    Investigated the structural pictorial properties of a children's version of The Family Environment Scale as a content validity study of the scale. Age differences in results between third- and seventh-grade children were confirmed, and social comprehension levels increased with age. Implications for present use and future research are discussed.…

  18. Extracellular α-synuclein induces sphingosine 1-phosphate receptor subtype 1 uncoupled from inhibitory G-protein leaving β-arrestin signal intact

    PubMed Central

    Zhang, Lifang; Okada, Taro; Badawy, Shaymaa Mohamed Mohamed; Hirai, Chihoko; Kajimoto, Taketoshi; Nakamura, Shun-ichi

    2017-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling. Treatment of human neuroblastoma cells with recombinant α-Syn caused S1P type 1 (S1P1) receptor-selective uncoupling from inhibitory G-protein (Gi) as determined by both functional and fluorescence resonance energy transfer (FRET)-based structural analyses. By contrast, α-Syn caused little or no effect on S1P2 receptor-mediated signalling. Both wild-type and α-Syn(A53T), a mutant found in familiar PD, caused uncoupling of S1P1 receptor, although α-Syn(A53T) showed stronger potency in uncoupling. Moreover, S1P1 receptor-mediated β-arrestin signal was unaltered by α-Syn(A53T). These results suggest that exogenous α-Syn modulates S1P1 receptor-mediated signalling from both Gi and β-arrestin signals into β-arrestin-biased signal. These findings uncovered a novel function of exogenous α-Syn in the cells. PMID:28300069

  19. Comparative study of goal contents and goal characteristics between medical and business students

    PubMed Central

    Park, Soowon; Kim, Ji Eun; Lee, Jun-Young; Shin, Jongho

    2016-01-01

    Purpose: Medical and business are one of the most popular majors among students, and both fields require intensive training to reach certain level of expertise. During the development of professionalism, goal can become a crucial role in psychological impetus. The purpose of this study is to compare goal contents, goal characteristics, and effect of goal characteristics on student’s major satisfaction between medical and business. Methods: A total of 193 undergraduate students (97 medical students, 96 business students) answered survey questions including goal contents, goal characteristics (goal autonomy, goal attainability, social value of goal) and satisfaction on their majors. Qualitative analysis of goal contents and quantitative analysis of goal characteristics, and their effects on student major satisfaction were performed. Results: Goal content analysis showed percentage of social concern goal was higher in medical students (25.8%) than business students (6.3%), whereas percentage of wealth goal was higher business students (24.0%) than medical students (3.1%). Among goal characteristics, goal attainability and social value of goal were higher in medical students than business students. In both groups, social value of goal was significantly predict major satisfaction. Conclusion: Goal contents and goal characteristics are different between medical and business students. Curriculum and educational interventions that concerning students’ goal and developing programs to enhance students’ social value of goal is necessary. PMID:26838564

  20. Reading in the Social Studies and Natural Science Content Area: A Phenomenological Study of the Beliefs, Attitudes, and Strategies Sixth and Seventh Grade Content Area Teachers Use to Teach below Grade Level Readers

    ERIC Educational Resources Information Center

    Clark, Lisa A.

    2011-01-01

    The purposes of this study were to identify the attitudes and beliefs content teachers have concerning teaching reading in the content area to below level readers and to identify specific instructional strategies that are used to teach students who are below grade level the content area material. Twelve participants were selected, using maximum…

  1. Study of Polyphenol Content and Antioxidant Capacity of Myrianthus Arboreus (Cecropiaceae) Root Bark Extracts

    PubMed Central

    Kasangana, Pierre Betu; Haddad, Pierre Selim; Stevanovic, Tatjana

    2015-01-01

    In order to evaluate the therapeutic potential of polyphenolic extracts from root bark of M. arboreus, we have determined the content of various polyphenols in aqueous and ethanol (EtOH) extract as well as two sub-fractions of the latter: ethyl acetate (EAc) and hexane (Hex). The total phenols, flavonoids, hydroxycinnamic acids and proanthocyanidins have been determined for all studied extracts/fractions by spectrophotometric methods. Both TP content (331.5 ± 2.5 mg GAE/g) and HCA content (201 ± 1.5 mg CAE/g) were determined to be the highest in EAc fraction of EtOH extract. All studied extracts were however determined to have a low content in flavonoids. The determination of antioxidant capacities of the studied extracts has also been performed by the following in vitro antioxidant tests: DPPH scavenging, phosphomolybdenum method and oxygen radical absorbance (ORACFl and ORACPRG) assay. The results of the DPPH free radical and ORACFl assays showed that there is no significant difference between the EAc fraction and Oligopin®, but the EAc fraction exhibited the highest antioxidant capacity as determined by the phosphomolybdenium method. In addition, the EtOH extract was determined to have the same antioxidant efficiency as the synthetic antioxidant BHT or commercial extract Oligopin® by phosphomolybdenum method. On the other hand, a positive correlation (r < 0.6) was found between different classes of polyphenols and the results of the phosphomolybdenum method, ORACFl as well as ORACPRG, except for the DPPH assay, for which a negative correlation was indicated (r < 0.62). Interestingly, it seems that the content in hydroxycinnamic acids played a big role in all assays with r < 0.9. According to the present study, EAc fraction and EtOH extract should be further studied for the potential use in the pharmaceutical and food industry. PMID:26783713

  2. Contextual and conceptual content analysis in the study of foreign policy decision making

    SciTech Connect

    Schlagheck, D.M.

    1985-01-01

    This dissertation focuses upon two related questions in the study of foreign policy decision making at the individual level: (1) How does a decision maker define the situation he/she confronts. and, (2) How can the research reliably establish that definition. The problem of context and how a decision maker defines it is shown to be a common thread running throughout the foreign policy literature, brought together in a manageable form by the operational code. The operational code is used to guide the application of a new, contextual and conceptual content analysis program in a case study of Henry A. Kissinger's definition of the situations he faced in the Vietnam and arms control negotiations. Kissinger's verbal behavior is examined, including his academic writing; speeches and interviews he gave while in office; his memoirs; and, addresses he has made since leaving public service. The content analysis program (Minnesota Contextural Content Analysis, MCCA) analyzes an individual's understanding of context based on her/his choice of language, and scores verbal behavior in four context categories: pragmatic (rational), analytical, emotional, and traditional. Results of the content analysis of Kissinger's definition of the Vietnam War and arms control talks are analyzed in terms of COPDAB events data to determine whether Kissinger's verbal behavior was events dependent; results are also evaluated in terms of other psycho-biographical and operational studies of Kissinger, as well.

  3. Framing deductive reasoning with emotional content: an fMRI study.

    PubMed

    Brunetti, M; Perrucci, M G; Di Naccio, M R; Ferretti, A; Del Gratta, C; Casadio, C; Romani, G L

    2014-06-01

    In the literature concerning the study of emotional effect on cognition, several researches highlight the mechanisms of reasoning ability and the influence of emotions on this ability. However, up to now, no neuroimaging study was specifically devised to directly compare the influence on reasoning performance of visual task-unrelated with semantic task-related emotional information. In the present functional fMRI study, we devised a novel paradigm in which emotionally negative vs. neutral visual stimuli (context) were used as primes, followed by syllogisms composed of propositions with emotionally negative vs. neutral contents respectively. Participants, in the MR scanner, were asked to assess the logical validity of the syllogisms. We have therefore manipulated the emotional state and arousal induced by the visual prime as well as the emotional interference exerted by the syllogism content. fMRI data indicated a medial prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex activation in conditions with negative context. Furthermore, a lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was observed. Finally, behavioral data confirmed the influence of emotional task-related stimuli on reasoning ability, since the performance was worse in conditions with syllogisms involving negative emotions. Therefore, on the basis of these data, we conclude that emotional states can impair the performance in reasoning tasks by means of the delayed general reactivity, whereas the emotional content of the target may require a larger amount of top-down resources to be processed.

  4. Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

    PubMed Central

    Lymperopoulos, Anastasios; Aukszi, Beatrix

    2017-01-01

    Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers (ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes (G protein-, and βarr1-dependent) at the AngII-activated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by AngII and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-“biased” blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan (and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.

  5. A case study: The original intentions of the designers of the science content standards

    NASA Astrophysics Data System (ADS)

    Eucker, Penelope Hudson

    This case study research examined the original intentions of the designers of the science content standards in the historical context of educational reforms and legislation. The content standards are the keystone of standards-based education. Originally, national science content standards were part of a cohesive program to increase the occurrence of quality science K--12. Through assessment policies set into motion by state and federal legislation, science curriculum is increasingly fixed and standardized. Scripting teachers is becoming more common. Unintended outcomes of standards-based education are prevalent in all classrooms. Recording the original intentions of the designers of the science content standards in a historical context is significant to document their beliefs and purposes. The shared beliefs of the six scholars included: (a) science had become overstuffed curriculum with students learning very few concepts; (b) science teachers required assistance to decide which concepts are most important for students to learn; (c) standards-based education will most likely endure for a very long time; (d) science is a specific way of knowing and inquiry must be part of science instruction; (e) few teachers teach to the science content standards. The scholars disagreed about whether the power to decide what to teach had moved from the classroom to the legislators and if standards-based education has preferentially helped some groups of students while diminishing the science education of others. Implications from the findings reveal the tension between a defined science content and the resultant assessment template that further trims the instructional range offered. Foreshadowing of increasing trend toward profits made from testing companies as state and federal legislation increase mandated assessments. Significantly, the educational research that clearly demonstrate many pathways lead to educated students such as the Eight-Year Study were suppressed in favor of

  6. The Social Studies Basic Skills Connection: Practical Strategies for Teaching Basic Skills in Conjunction with Social Studies Content.

    ERIC Educational Resources Information Center

    Missouri State Dept. of Education, Jefferson City.

    Arranged in two parts, this guide introduces elementary and secondary social studies teachers to a variety of methods for integrating social studies content and basic skills instruction. Chapter I defines basic skills as the skills an individual needs to become a self-directed learner, communicate clearly, and make reasoned decisions, and presents…

  7. Study on the effect of polydimethylsiloxane from the viewpoint of oxygen content in oil.

    PubMed

    Yawata, Miho; Iwahashi, Maiko; Hori, Ryuji; Shiramasa, Hiroshi; Totani, Nagao

    2014-01-01

    It has been reported that polydimethylsiloxane (PDMS) inhibits oxygen dissolution into oil by forming a monolayer on the surface of the oil, thereby reducing thermal oxidation. In the present study, the distribution of PDMS was determined by the inductively coupled plasma atomic emission spectroscopy in standing PDMS-containing canola oil. PDMS did not disperse in the oil uniformly, but there was a tendency that the PDMS concentration decreased as the depth of oil increased, and the concentration of the bottom part was the lowest. When canola oil was covered with PDMS by dropping it gently on the surface of the oil and kept at 60°C, the oxygen content and oxidation of the oil were lower than those of the control canola oil. PDMS-containing canola oil and canola oil were heated with stirring from room temperature to 180°C, and then allowed to stand while cooling. Oxygen contents of both oils increased up to 120°C then dropped abruptly. While cooling, oxygen contents sharply increased at 100°C and approached the saturation content, although the increase for PDMS-containing canola oil was a little slow. Likewise, the thermal treatment of PDMS-containing canola oil and canola oil at 180°C for 1 h under stirring was repeated 5 times with standing intervals for 2-3 days at room temperature. Oxidation of the former was less than that of the latter in spite of its high oxygen content. In conclusion, the oxygen content of oil with/without PDMS addition increased, but oxidation of PDMS-containing canola oil was inhibited both during heating and standing with intermittent heating. It was suggested that PDMS exerted its antioxidative effect regardless of whether it covered the oil or was dispersed in it.

  8. Content-based versus semantic-based retrieval: an LIDC case study

    NASA Astrophysics Data System (ADS)

    Jabon, Sarah A.; Raicu, Daniela S.; Furst, Jacob D.

    2009-02-01

    Content based image retrieval is an active area of medical imaging research. One use of content based image retrieval (CBIR) is presentation of known, reference images similar to an unknown case. These comparison images may reduce the radiologist's uncertainty in interpreting that case. It is, therefore, important to present radiologists with systems whose computed-similarity results correspond to human perceived-similarity. In our previous work, we developed an open-source CBIR system that inputs a computed tomography (CT) image of a lung nodule as a query and retrieves similar lung nodule images based on content-based image features. In this paper, we extend our previous work by studying the relationships between the two types of retrieval, content-based and semantic-based, with the final goal of integrating them into a system that will take advantage of both retrieval approaches. Our preliminary results on the Lung Image Database Consortium (LIDC) dataset using four types of image features, seven radiologists' rated semantic characteristics and two simple similarity measures show that a substantial number of nodules identified as similar based on image features are also identified as similar based on semantic characteristics. Furthermore, by integrating the two types of features, the similarity retrieval improves with respect to certain nodule characteristics.

  9. Study on the water content measurement of tomatoes by near infrared technique

    NASA Astrophysics Data System (ADS)

    Jiang, Huanyu; Ying, Yibin; Bao, Yingshi

    2005-11-01

    Near infrared (NIR) spectroscopy is a promising technique for nondestructive measurement of farm products quality measurement and information acquisition. The objective of this research was to study the potential of NIR diffuse reflectance spectroscopy as a way for nondestructive measurement of the water content of tomato leaves. A total of 120 leaves were collected as experimental materials, 80 of them were used to form a calibration data set. In order to set up a calibration model, NIR spectral data were collected in the spectral region between 800 nm and 2500 nm by NIR spectrometer of Nicolet Corporation, and water content of tomato leaves by a drying chest, four different mathematical treatments were used in spectrums processing: different wavelength range, baseline correction, smoothing, first and second derivative. Depending on data preprocessing and PLS analysis, we can get best prediction model when we select original spectra by baseline correction at full wavelength range (800-2500nm), the best model of water content has a root mean square error of prediction (RMSEP) of 1.91, a root mean square error of calibration (RMSEC) of 0.731 and a calibration correlation coefficient (R) value of 0.96265. It is conclude that the FTNIR method with Smart Near-IR UpDRIFT accessory can accurate estimate the water content in tomato leaves.

  10. Content analysis and thematic analysis: Implications for conducting a qualitative descriptive study.

    PubMed

    Vaismoradi, Mojtaba; Turunen, Hannele; Bondas, Terese

    2013-09-01

    Qualitative content analysis and thematic analysis are two commonly used approaches in data analysis of nursing research, but boundaries between the two have not been clearly specified. In other words, they are being used interchangeably and it seems difficult for the researcher to choose between them. In this respect, this paper describes and discusses the boundaries between qualitative content analysis and thematic analysis and presents implications to improve the consistency between the purpose of related studies and the method of data analyses. This is a discussion paper, comprising an analytical overview and discussion of the definitions, aims, philosophical background, data gathering, and analysis of content analysis and thematic analysis, and addressing their methodological subtleties. It is concluded that in spite of many similarities between the approaches, including cutting across data and searching for patterns and themes, their main difference lies in the opportunity for quantification of data. It means that measuring the frequency of different categories and themes is possible in content analysis with caution as a proxy for significance.

  11. High Water Contents in the Siberian Cratonic Mantle: An FTIR Study of Udachnaya Peridotite Xenoliths

    NASA Technical Reports Server (NTRS)

    Doucet, Luc S.; Peslier, Anne H.; Ionov, Dimitri A.; Brandon, Alan D.; Golovin, Alexander V.; Ashchepkov, Igor V.

    2013-01-01

    Water is believed to be a key factor controlling the long-term stability of cratonic lithosphere, but mechanisms responsible for the water content distribution in the mantle remain poorly constrained. Water contents were obtained by FTIR in olivine, pyroxene and garnet for 20 well-characterized peridotite xenoliths from the Udachnaya kimberlite (central Siberian craton) and equilibrated at 2-7 GPa. Water contents in minerals do not appear to be related to interaction with the host kimberlite. Diffusion modeling indicates that the core of olivines preserved their original water contents. The Udachnaya peridotites show a broad range of water contents in olivine (6.5 +/- 1.1 to 323 +- 65 ppm H2O (2 sigma)), and garnet (0 - 23 +/- 6 ppm H2O). The water contents of olivine and garnet are positively correlated with modal clinopyroxene, garnet and FeO in olivine. Water-rich garnets are also rich in middle rare earth elements. This is interpreted as the result of interaction between residual peridotites and water rich-melts, consistent with modal and cryptic metasomatism evidenced in the Siberian cratonic mantle. The most water-rich Udachnaya minerals contain 2 to 3 times more water than those from the Kaapvaal craton, the only craton with an intact mantle root for which water data is available. The highest water contents in olivine and orthopyroxene in this study (>= 300 ppm) are found at the bottom of the lithosphere (> 6.5 GPa). This is in contrast with the Kaapvaal craton where the olivines of peridotites equilibrated at > 6.4 GPa have < 1 ppm H2O. The latter "dry" olivine may make the base of the Kaapvaal cratonic root strong and thus protects it from erosion by the convective mantle The calculated viscosity for water-rich Udachnaya peridotites at > 6 GPa is lower or similar (8.4× 10(exp 16) to 8.0× 10(exp 18) Pa./s) to that of the asthenosphere (<= 3.7x10(exp 18) Pa./s ). Such lithologies would not be able to resist delamination by the convecting asthenosphere

  12. When Educational Material Is Delivered: A Mixed Methods Content Validation Study of the Information Assessment Method

    PubMed Central

    2017-01-01

    Background The Information Assessment Method (IAM) allows clinicians to report the cognitive impact, clinical relevance, intention to use, and expected patient health benefits associated with clinical information received by email. More than 15,000 Canadian physicians and pharmacists use the IAM in continuing education programs. In addition, information providers can use IAM ratings and feedback comments from clinicians to improve their products. Objective Our general objective was to validate the IAM questionnaire for the delivery of educational material (ecological and logical content validity). Our specific objectives were to measure the relevance and evaluate the representativeness of IAM items for assessing information received by email. Methods A 3-part mixed methods study was conducted (convergent design). In part 1 (quantitative longitudinal study), the relevance of IAM items was measured. Participants were 5596 physician members of the Canadian Medical Association who used the IAM. A total of 234,196 ratings were collected in 2012. The relevance of IAM items with respect to their main construct was calculated using descriptive statistics (relevance ratio R). In part 2 (qualitative descriptive study), the representativeness of IAM items was evaluated. A total of 15 family physicians completed semistructured face-to-face interviews. For each construct, we evaluated the representativeness of IAM items using a deductive-inductive thematic qualitative data analysis. In part 3 (mixing quantitative and qualitative parts), results from quantitative and qualitative analyses were reviewed, juxtaposed in a table, discussed with experts, and integrated. Thus, our final results are derived from the views of users (ecological content validation) and experts (logical content validation). Results Of the 23 IAM items, 21 were validated for content, while 2 were removed. In part 1 (quantitative results), 21 items were deemed relevant, while 2 items were deemed not relevant

  13. Content Area Reading Instruction for Secondary Teacher Candidates: A Case Study of a State-Required Online Content Area Reading Course

    ERIC Educational Resources Information Center

    Biggs, Brad

    2014-01-01

    This dissertation examined in a state-required, online preservice teacher course in content area reading instruction (CARI) at a large land-grant university in Minnesota. Few studies have been published to date on revitalized literacy teacher preparation efforts in CARI (See Vagle, Dillon, Davison-Jenkins, & LaDuca, 2005; Dillon, O'Brien,…

  14. Middle school students' earthquake content and preparedness knowledge - A mixed method study

    NASA Astrophysics Data System (ADS)

    Henson, Harvey, Jr.

    The purpose of this study was to assess the effect of earthquake instruction on students' earthquake content and preparedness for earthquakes. This study used an innovative direct instruction on earthquake science content and concepts with an inquiry-based group activity on earthquake safety followed by an earthquake simulation and preparedness video to help middle school students understand and prepare for the regional seismic threat. A convenience sample of 384 sixth and seventh grade students at two small middle schools in southern Illinois was used in this study. Qualitative information was gathered using open-ended survey questions, classroom observations, and semi-structured interviews. Quantitative data were collected using a 21 item content questionnaire administered to test students' General Earthquake Knowledge, Local Earthquake Knowledge, and Earthquake Preparedness Knowledge before and after instruction. A pre-test and post-test survey Likert scale with 21 items was used to collect students' perceptions and attitudes. Qualitative data analysis included quantification of student responses to the open-ended questions and thematic analysis of observation notes and interview transcripts. Quantitative datasets were analyzed using descriptive and inferential statistical methods, including t tests to evaluate the differences in means scores between paired groups before and after interventions and one-way analysis of variance (ANOVA) to test for differences between mean scores of the comparison groups. Significant mean differences between groups were further examined using a Dunnett's C post hoc statistical analysis. Integration and interpretation of the qualitative and quantitative results of the study revealed a significant increase in general, local and preparedness earthquake knowledge among middle school students after the interventions. The findings specifically indicated that these students felt most aware and prepared for an earthquake after an

  15. βArrestins in cardiac G protein-coupled receptor signaling and function: partners in crime or "good cop, bad cop"?

    PubMed

    Lymperopoulos, Anastasios; Negussie, Shmuel

    2013-12-18

    βArrestin (βarr)-1 and -2 (βarrs) (or Arrestin-2 and -3, respectively) are universal G protein-coupled receptor (GPCR) adapter proteins expressed abundantly in extra-retinal tissues, including the myocardium. Both were discovered in the lab of the 2012 Nobel Prize in Chemistry co-laureate Robert Lefkowitz, initially as terminators of signaling from the β-adrenergic receptor (βAR), a process known as functional desensitization. They are now known to switch GPCR signaling from G protein-dependent to G protein-independent, which, in the case of βARs and angiotensin II type 1 receptor (AT1R), might be beneficial, e.g., anti-apoptotic, for the heart. However, the specific role(s) of each βarr isoform in cardiac GPCR signaling and function (or dysfunction in disease), remain unknown. The current consensus is that, whereas both βarr isoforms can desensitize and internalize cardiac GPCRs, they play quite different (even opposing in certain instances) roles in the G protein-independent signaling pathways they initiate in the cardiovascular system, including in the myocardium. The present review will discuss the current knowledge in the field of βarrs and their roles in GPCR signaling and function in the heart, focusing on the three most important, for cardiac physiology, GPCR types (β1AR, β2AR & AT1R), and will also highlight important questions that currently remain unanswered.

  16. Marker-trait association study for protein content in chickpea (Cicer arietinum L.).

    PubMed

    Jadhav, A A; Rayate, S J; Mhase, L B; Thudi, M; Chitikineni, A; Harer, P N; Jadhav, A S; Varshney, R K; Kulwal, P L

    2015-06-01

    Chickpea (Cicer arietinum L.) is the second most important cool season food legume cultivated in arid and semiarid regions of the world. The objective of the present study was to study variation for protein content in chickpea germplasm, and to find markers associated with it. A set of 187 genotypes comprising both international and exotic collections, and representing both desi and kabuli types with protein content ranging from 13.25% to 26.77% was used. Twenty-three SSR markers representing all eight linkage groups (LG) amplifying 153 loci were used for the analysis. Population structure analysis identified three subpopulations, and corresponding Q values of principal components were used to take care of population structure in the analysis which was performed using general linear and mixed linear models. Marker-trait association (MTA) analysis identified nine significant associations representing four QTLs in the entire population. Subpopulation analyses identified ten significant MTAs representing five QTLs, four of which were common with that of the entire population. Two most significant QTLs linked with markers TR26.205 and CaM1068.195 were present on LG3 and LG5. Gene ontology search identified 29 candidate genes in the region of significant MTAs on LG3. The present study will be helpful in concentrating on LG3 and LG5 for identification of closely linked markers for protein content in chickpea and for their use in molecular breeding programme for nutritional quality improvement.

  17. A content validity study of signs, symptoms and diseases/health problems expressed in LIBRAS1

    PubMed Central

    Aragão, Jamilly da Silva; de França, Inacia Sátiro Xavier; Coura, Alexsandro Silva; de Sousa, Francisco Stélio; Batista, Joana D'arc Lyra; Magalhães, Isabella Medeiros de Oliveira

    2015-01-01

    Objectives: to validate the content of signs, symptoms and diseases/health problems expressed in LIBRAS for people with deafness Method: methodological development study, which involved 36 people with deafness and three LIBRAS specialists. The study was conducted in three stages: investigation of the signs, symptoms and diseases/health problems, referred to by people with deafness, reported in a questionnaire; video recordings of how people with deafness express, through LIBRA, the signs, symptoms and diseases/health problems; and validation of the contents of the recordings of the expressions by LIBRAS specialists. Data were processed in a spreadsheet and analyzed using univariate tables, with absolute frequencies and percentages. The validation results were analyzed using the Content Validity Index (CVI). Results: 33 expressions in LIBRAS, of signs, symptoms and diseases/health problems were evaluated, and 28 expressions obtained a satisfactory CVI (1.00). Conclusions: the signs, symptoms and diseases/health problems expressed in LIBRAS presented validity, in the study region, for health professionals, especially nurses, for use in the clinical anamnesis of the nursing consultation for people with deafness. PMID:26625991

  18. Injection Drug User Quality of Life Scale (IDUQOL): Findings from a content validation study

    PubMed Central

    Hubley, Anita M; Palepu, Anita

    2007-01-01

    Background Quality of life studies among injection drug users have primarily focused on health-related measures. The chaotic life-style of many injection drug users (IDUs), however, extends far beyond their health, and impacts upon social relationships, employment opportunities, housing, and day to day survival. Most current quality of life instruments do not capture the realities of people living with addictions. The Injection Drug Users' Quality of Life Scale (IDUQOL) was developed to reflect the life areas of relevance to IDUs. The present study examined the content validity of the IDUQOL using judgmental methods based on subject matter experts' (SMEs) ratings of various elements of this measure (e.g., appropriateness of life areas or items, names and descriptions of life areas, instructions for administration and scoring). Methods Six SMEs were provided with a copy of the IDUQOL and its administration and scoring manual and a detailed content validation questionnaire. Two commonly used judgmental measures of inter-rater agreement, the Content Validity Index (CVI) and the Average Deviation Mean Index (ADM), were used to evaluate SMEs' agreement on ratings of IDUQOL elements. Results A total of 75 elements of the IDUQOL were examined. The CVI results showed that all elements were endorsed by the required number of SMEs or more. The ADM results showed that acceptable agreement (i.e., practical significance) was obtained for all elements but statistically significant agreement was missed for nine elements. For these elements, SMEs' feedback was examined for ways to improve the elements. Open-ended feedback also provided suggestions for other revisions to the IDUQOL. Conclusion The results of the study provided strong evidence in support of the content validity of the IDUQOL and direction for the revision of some IDUQOL elements. PMID:17663783

  19. Alterations of Myelin Content in Parkinson’s Disease: A Cross-Sectional Neuroimaging Study

    PubMed Central

    Sojkova, Jitka; Hurley, Samuel; Kecskemeti, Steven; Okonkwo, Ozioma; Bendlin, Barbara B.; Theisen, Frances; Johnson, Sterling C.; Alexander, Andrew L.; Gallagher, Catherine L.

    2016-01-01

    Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain’s myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson’s disease. PMID:27706215

  20. Qualitative study of ethanol content in tequilas by Raman spectroscopy and principal component analysis

    NASA Astrophysics Data System (ADS)

    Frausto-Reyes, C.; Medina-Gutiérrez, C.; Sato-Berrú, R.; Sahagún, L. R.

    2005-09-01

    Using Raman spectroscopy, with an excitation radiation source of 514.5 nm, and principal component analysis (PCA) was elaborated a method to study qualitatively the ethanol content in tequila samples. This method is based in the OH region profile (water) of the Raman spectra. Also, this method, using the fluorescence background of the Raman spectra, can be used to distinguish silver tequila from aged tequilas. The first three PCs of the Raman spectra, that provide the 99% of the total variance of the data set, were used for the samples classification. The PCA1 and PCA2 are related with the water (or ethanol) content of the sample, whereas the PCA3 is related with the fluorescence background of the Raman spectra.

  1. Qualitative study of ethanol content in tequilas by Raman spectroscopy and principal component analysis.

    PubMed

    Frausto-Reyes, C; Medina-Gutiérrez, C; Sato-Berrú, R; Sahagún, L R

    2005-09-01

    Using Raman spectroscopy, with an excitation radiation source of 514.5 nm, and principal component analysis (PCA) was elaborated a method to study qualitatively the ethanol content in tequila samples. This method is based in the OH region profile (water) of the Raman spectra. Also, this method, using the fluorescence background of the Raman spectra, can be used to distinguish silver tequila from aged tequilas. The first three PCs of the Raman spectra, that provide the 99% of the total variance of the data set, were used for the samples classification. The PCA1 and PCA2 are related with the water (or ethanol) content of the sample, whereas the PCA3 is related with the fluorescence background of the Raman spectra.

  2. An Experimental Study to the Seismoelectric Responses of Unfrozen Water Content

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Yuan, L.; Song, L.

    2014-12-01

    For many sections of the Qing-Cang railway line located in the permafrost regions, the monitoring of freeze-thaw cycling is a main mean for the railway operation as the seasons of the permafrost are the main factors that weaken the railway bed. The unfrozen water content is one of the most important parameters in the field monitoring and laboratory research of the freeze-thaw cycling of the permafrost. It has been already shown that the propagation of seismic waves inside a homogeneous porous medium induces a localized seismoelectric conversion field that moves along with the seismic waves, because of relative fluid motion in the pores. As the field is water saturation related, we initially conducted an experiment to study the seismoelectric responses varying with unfrozen water content. In the experiment, a cylinder frozen soil model which is heated gradually from bottom is set up to model a decrease temperature field, corresponding to that the unfrozen water content, from bottom to top. Then a seismic wave field is excited by a ultra acoustic transducer located on the top of the model and seismoelectric conversion responses are measured with a set of electrodes layout along the axis direction of the model with 1cm depth inside the model. At the same time, the temperature at each electrode is measured by a heat sensitive resistance near the electrode. Keeping the heating from bottom of the model, the measurement is performed at a fixed time period until the temperature of each electrode is increasing over zero degree centigrade. The experiment observations show: 1) The travel velocity of the seismoelectric signals is decreasing with increasing of temperature, or that of unfrozen water content, which also verify the flexibility of the experiment. 2) The amplitudes of the seismoelectric signals generally increase with that of temperature, corresponding to that of unfrozen water content increasing. 3) As the seimoelectric responses are measured with point

  3. Low-field nuclear magnetic resonance for the in vivo study of water content in trees.

    PubMed

    Yoder, Jacob; Malone, Michael W; Espy, Michelle A; Sevanto, Sanna

    2014-09-01

    Nuclear magnetic resonance (NMR) and magnetic resonance imaging have long been used to study water content in plants. Approaches have been primarily based on systems using large magnetic fields (~1 T) to obtain NMR signals with good signal-to-noise. This is because the NMR signal scales approximately with the magnetic field strength squared. However, there are also limits to this approach in terms of realistic physiological configuration or those imposed by the size and cost of the magnet. Here we have taken a different approach--keeping the magnetic field low to produce a very light and inexpensive system, suitable for bulk water measurements on trees less than 5 cm in diameter, which could easily be duplicated to measure on many trees or from multiple parts of the same tree. Using this system we have shown sensitivity to water content in trees and their cuttings and observed a diurnal signal variation in tree water content in a greenhouse. We also demonstrate that, with calibration and modeling of the thermal polarization, the system is reliable under significant temperature variation.

  4. Low-field nuclear magnetic resonance for the in vivo study of water content in trees

    SciTech Connect

    Yoder, Jacob; Malone, Michael W.; Espy, Michelle A.; Sevanto, Sanna

    2014-09-15

    Nuclear magnetic resonance (NMR) and magnetic resonance imaging have long been used to study water content in plants. Approaches have been primarily based on systems using large magnetic fields (∼1 T) to obtain NMR signals with good signal-to-noise. This is because the NMR signal scales approximately with the magnetic field strength squared. However, there are also limits to this approach in terms of realistic physiological configuration or those imposed by the size and cost of the magnet. Here we have taken a different approach – keeping the magnetic field low to produce a very light and inexpensive system, suitable for bulk water measurements on trees less than 5 cm in diameter, which could easily be duplicated to measure on many trees or from multiple parts of the same tree. Using this system we have shown sensitivity to water content in trees and their cuttings and observed a diurnal signal variation in tree water content in a greenhouse. We also demonstrate that, with calibration and modeling of the thermal polarization, the system is reliable under significant temperature variation.

  5. Luminescence studies in InxGa1-xN epitaxial layers with different indium contents

    NASA Astrophysics Data System (ADS)

    Wu, T. Y.; Chang, C. C.; Tiong, K. K.; Lee, Y. C.; Hu, S. Y.; Lin, L. Y.; Lin, T. Y.; Feng, Z. C.

    2013-08-01

    The optical properties of InxGa1-xN epitaxial layers (x = 0.02, 0.04, 0.11, 0.15, 0.30 and 0.33) grown by metalorganic chemical vapor deposition (MOCVD) have been investigated by temperature-dependent photoluminescence (PL) measurement. The surface morphologies of InGaN samples are studied by scanning electron microscopy (SEM) images. The PL feature at 12 K has shown an increase in full-width at half-maximum (FWHM) with increasing In content. An anomalous S-shaped temperature dependence of the PL peak energy exhibited by InGaN films with higher In content enabled the evaluation of the exciton localization energy. The broadened FWHM and S-shaped emission shift are attributed to larger compositional fluctuation due to compositional inhomogeneity of In. Additionally, the luminescence mechanism relating to the phase separation has to be considered for the much larger FWHM value and the pronounced S-shaped behavior for the InGaN samples with In content of 0.30 and 0.33.

  6. Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases.

    PubMed Central

    Roggli, V L; Pratt, P C; Brody, A R

    1986-01-01

    Diseases associated with asbestos exposure include asbestosis, malignant mesothelioma, carcinoma of the lung, and parietal pleural plaques. In this study the asbestos content of lung tissue was examined in groups of cases representing each of these diseases and in several cases with non-occupational idiopathic pulmonary fibrosis. Asbestos bodies (AB), which are the hallmark of asbestos exposure, were present in the lungs of virtually everyone in the general population and present at increased levels in individuals with asbestos associated diseases. The highest numbers of AB occurred in individuals with asbestosis, all of whom had levels greater than or equal to 2000 ABs/g wet lung tissue. Every case with a content of 100,000 ABs/g or higher had asbestosis. Intermediate levels occurred in individuals with malignant mesothelioma and the lowest levels in patients with parietal pleural plaques. There was no overlap between the asbestos content of lung tissue from patients with asbestosis and those with idiopathic pulmonary fibrosis. Lung cancer was present in half the patients with asbestosis, and the distribution of histological patterns did not differ from that in patients with lung cancer without asbestosis. The asbestos body content in patients with lung cancer was highly variable. Control cases had values within our previously established normal range (0-20 ABs/g). There was a significant correlation (p less than 0.001) between AB counted by light microscope and AB and uncoated fibres counted by scanning electron microscopy. The previous observation that the vast majority of asbestos bodies isolated from human tissues have an amphibole core was confirmed. Images PMID:3947558

  7. A Candidate Gene-Based Association Study of Tocopherol Content and Composition in Rapeseed (Brassica napus)

    PubMed Central

    Fritsche, Steffi; Wang, Xingxing; Li, Jinquan; Stich, Benjamin; Kopisch-Obuch, Friedrich J.; Endrigkeit, Jessica; Leckband, Gunhild; Dreyer, Felix; Friedt, Wolfgang; Meng, Jinling; Jung, Christian

    2012-01-01

    Rapeseed (Brassica napus L.) is the most important oil crop of temperate climates. Rapeseed oil contains tocopherols, also known as vitamin E, which is an indispensable nutrient for humans and animals due to its antioxidant and radical scavenging abilities. Moreover, tocopherols are also important for the oxidative stability of vegetable oils. Therefore, seed oil with increased tocopherol content or altered tocopherol composition is a target for breeding. We investigated the role of nucleotide variations within candidate genes from the tocopherol biosynthesis pathway. Field trials were carried out with 229 accessions from a worldwide B. napus collection which was divided into two panels of 96 and 133 accessions. Seed tocopherol content and composition were measured by HPLC. High heritabilities were found for both traits, ranging from 0.62 to 0.94. We identified polymorphisms by sequencing selected regions of the tocopherol genes from the 96 accession panel. Subsequently, we determined the population structure (Q) and relative kinship (K) as detected by genotyping with genome-wide distributed SSR markers. Association studies were performed using two models, the structure-based GLM + Q and the PK-mixed model. Between 26 and 12 polymorphisms within two genes (BnaX.VTE3.a, BnaA.PDS1.c) were significantly associated with tocopherol traits. The SNPs explained up to 16.93% of the genetic variance for tocopherol composition and up to 10.48% for total tocopherol content. Based on the sequence information we designed CAPS markers for genotyping the 133 accessions from the second panel. Significant associations with various tocopherol traits confirmed the results from the first experiment. We demonstrate that the polymorphisms within the tocopherol genes clearly impact tocopherol content and composition in B. napus seeds. We suggest that these nucleotide variations may be used as selectable markers for breeding rapeseed with enhanced tocopherol quality. PMID:22740840

  8. A candidate gene-based association study of tocopherol content and composition in rapeseed (Brassica napus).

    PubMed

    Fritsche, Steffi; Wang, Xingxing; Li, Jinquan; Stich, Benjamin; Kopisch-Obuch, Friedrich J; Endrigkeit, Jessica; Leckband, Gunhild; Dreyer, Felix; Friedt, Wolfgang; Meng, Jinling; Jung, Christian

    2012-01-01

    Rapeseed (Brassica napus L.) is the most important oil crop of temperate climates. Rapeseed oil contains tocopherols, also known as vitamin E, which is an indispensable nutrient for humans and animals due to its antioxidant and radical scavenging abilities. Moreover, tocopherols are also important for the oxidative stability of vegetable oils. Therefore, seed oil with increased tocopherol content or altered tocopherol composition is a target for breeding. We investigated the role of nucleotide variations within candidate genes from the tocopherol biosynthesis pathway. Field trials were carried out with 229 accessions from a worldwide B. napus collection which was divided into two panels of 96 and 133 accessions. Seed tocopherol content and composition were measured by HPLC. High heritabilities were found for both traits, ranging from 0.62 to 0.94. We identified polymorphisms by sequencing selected regions of the tocopherol genes from the 96 accession panel. Subsequently, we determined the population structure (Q) and relative kinship (K) as detected by genotyping with genome-wide distributed SSR markers. Association studies were performed using two models, the structure-based GLM + Q and the PK-mixed model. Between 26 and 12 polymorphisms within two genes (BnaX.VTE3.a, BnaA.PDS1.c) were significantly associated with tocopherol traits. The SNPs explained up to 16.93% of the genetic variance for tocopherol composition and up to 10.48% for total tocopherol content. Based on the sequence information we designed CAPS markers for genotyping the 133 accessions from the second panel. Significant associations with various tocopherol traits confirmed the results from the first experiment. We demonstrate that the polymorphisms within the tocopherol genes clearly impact tocopherol content and composition in B. napus seeds. We suggest that these nucleotide variations may be used as selectable markers for breeding rapeseed with enhanced tocopherol quality.

  9. Accuracy of a self-collection kit for the microbiological study of the vaginal content.

    PubMed

    Passos, Mauro Romero L; Varella, Renata Q; Barreto, Nero A; Garcia, Maria Luiza; Giraldo, Paulo C

    2007-04-01

    Diagnosis of vaginal discharge is frequently performed in an empirical way, leading to inadequate treatment. This study tested the accuracy of a self-collection kit for microbiological study of the vaginal content. One hundred and forty-two women of Family Health Program units in Niterói and Piraí cities were enrolled in order to have their vaginal content studied. A brief explanation and a self-collection kit were provided in order to sample the vaginal content. The self-collection kit was composed of one empty plastic tube, two glass slides, a long handle cytobrush, an identification card and guideline notes. The vaginal sample was applied on the glass slides by the women and stained by Gram technique. A second sampling was done by the medical personnel. The microbiological diagnosis in a blinded analysis was made under optical microscopy. A validation diagnosis test was done taking the medical collection results as a gold standard. A total of 106 women had followed the protocol and were included in the study. Microbiological analysis was unsatisfactory in 12 cases (6 cases of self-collection material and 6 cases of medical collection). The microbiological analyses in the self-collection and in the medical collection material were respectively: bacterial vaginosis in 21.7% and 17.9%, non bacillar flora in 10.3% and 11.3%, vaginal trichomoniasis in 5.66% and 5.6%, candidiasis in 3.78% and 2.8% and a normal microbiota in 52.8% and 56.6%. The Kappa coefficient suggested a "very good correlation" of the microbiological results between the two methods of collection (K=0.7945). The self-collection kit provides samples for microbiological analysis of the vaginal microbiota as good as medical collection.

  10. Textbooks Content Analysis of Social Studies and Natural Sciences of Secondary School Based on Emotional Intelligence Components

    ERIC Educational Resources Information Center

    Babaei, Bahare; Abdi, Ali

    2014-01-01

    The aim of this study is to analyze the content of social studies and natural sciences textbooks of the secondary school on the basis of the emotional intelligence components. In order to determine and inspect the emotional intelligence components all of the textbooks content (including texts, exercises, and illustrations) was examined based on…

  11. A case study of alternatively trained science teachers: Attainment of pedagogical content knowledge

    NASA Astrophysics Data System (ADS)

    Duncan, Benjamin R.

    Elements essential to effective teaching are closely aligned with the domains of a teacher's pedagogical content knowledge (PCK) (Park & Oliver, 2008). Often, alternatively trained teachers enter the teaching profession lacking exposure to pedagogical events that allow these educators opportunities to reflect on their practice and construction of their PCK (Friedrichsen et al., 2007); yet little is known about the knowledge of experienced alternatively trained educators and the complexities associated with their PCK development. The purpose of this study was to describe the nature and sources of alternatively trained secondary school science teachers' PCK after gaining classroom experience. The Park and Oliver (2008) hexagon PCK model was used as the theoretical framework. A case study of two experienced secondary science teachers at a school in the southeastern region of the United States was conducted. Data were collected from multiple sources, such as interviews, classroom observations, participant field journals, lesson plans, classroom assignments, classroom assessments, and researcher's field notes. Data analysis was conducted using the constant comparative method, qualitative deductive analysis, and a content representation. The results showed that experienced alternatively trained science teachers' PCK development was heavily influenced by each teacher's orientation to science teaching. Alternatively trained science teachers compensated for their lack of pedagogical training by relying heavily upon their content knowledge, their knowledge of students, and past experiences. Even after gaining years of experience in a school setting, alternatively trained teachers still lacked familiarity with traditional educational terminology and practices, rather relying upon instructional approaches and techniques independently acquired while each teacher was in "survival" mode. This study provides several implications for teacher preparation, research, and policy.

  12. Multi-technique study of a ceramic archaeological artifact and its content.

    PubMed

    Legnaioli, S; Garcia, F Anabitarte; Andreotti, A; Bramanti, E; Pace, D Díaz; Formola, S; Lorenzetti, G; Martini, M; Pardini, L; Ribechini, E; Sibilia, E; Spiniello, R; Palleschi, V

    2013-01-01

    In this paper we report the results of a study performed with different physical and chemical methods on a ceramic vase originally attributed to the I century CE. The joint use of infrared spectroscopic analysis and laser techniques, as well as pyrolysis-gas chromatography coupled with mass spectrometry and thermoluminescence, allowed us to characterize the vase material and its content. The chemical data were combined with morphological and stylistic examinations of the object and helped in defining its actual geographical and chronological pertinence.

  13. Multi-technique study of a ceramic archaeological artifact and its content

    NASA Astrophysics Data System (ADS)

    Legnaioli, S.; Garcia, F. Anabitarte; Andreotti, A.; Bramanti, E.; Pace, D. Díaz; Formola, S.; Lorenzetti, G.; Martini, M.; Pardini, L.; Ribechini, E.; Sibilia, E.; Spiniello, R.; Palleschi, V.

    In this paper we report the results of a study performed with different physical and chemical methods on a ceramic vase originally attributed to the I century CE. The joint use of infrared spectroscopic analysis and laser techniques, as well as pyrolysis-gas chromatography coupled with mass spectrometry and thermoluminescence, allowed us to characterize the vase material and its content. The chemical data were combined with morphological and stylistic examinations of the object and helped in defining its actual geographical and chronological pertinence.

  14. The Use of Lesson Study Combined with Content Representation in the Planning of Physics Lessons During Field Practice to Develop Pedagogical Content Knowledge

    NASA Astrophysics Data System (ADS)

    Juhler, Martin Vogt

    2016-08-01

    Recent research, both internationally and in Norway, has clearly expressed concerns about missing connections between subject-matter knowledge, pedagogical competence and real-life practice in schools. This study addresses this problem within the domain of field practice in teacher education, studying pre-service teachers' planning of a Physics lesson. Two means of intervention were introduced. The first was lesson study, which is a method for planning, carrying out and reflecting on a research lesson in detail with a learner and content-centered focus. This was used in combination with a second means, content representations, which is a systematic tool that connects overall teaching aims with pedagogical prompts. Changes in teaching were assessed through the construct of pedagogical content knowledge (PCK). A deductive coding analysis was carried out for this purpose. Transcripts of pre-service teachers' planning of a Physics lesson were coded into four main PCK categories, which were thereafter divided into 16 PCK sub-categories. The results showed that the intervention affected the pre-service teachers' potential to start developing PCK. First, they focused much more on categories concerning the learners. Second, they focused far more uniformly in all of the four main categories comprising PCK. Consequently, these differences could affect their potential to start developing PCK.

  15. [Study on estimation of deserts soil total phosphorus content from thermal-infrared emissivity].

    PubMed

    Hou, Yan-jun; Tiyip, Tashpolat; Zhang, Fei; Sawut, Mamat; Nurmemet, Ilyas

    2015-02-01

    Soil phosphorus provides nutrient elements for plants, is one of important parameters for evaluating soil quality. The traditional method for soil total phosphorus content (STPC) measurement is not effective and time-consuming. However, remote sensing (RS) enables us to determine STPC in a fast and efficient way. Studies on the estimation of STPC in near-infrared spectroscopy have been developed by scholars, but model accuracy is still poor due to the low absorption coefficient and unclear absorption peak of soil phosphorus in near-infrared. In order to solve the deficiency which thermal-infrared emissivity estimate desert soil total phosphorus content, and could improve precision of estimation deserts soil total phosphorus. In this paper, characteristics of soil thermal-infrared emissivity are analyzed on the basis of laboratory processing and spectral measurement of deserts soil samples from the eastern Junggar Basin. Furthermore, thermal-infrared emissivity based RS models for STPC estimation are established and accuracy assessed. Results show that: when STPC is higher than 0.200 g x kg(-1), the thermal-infrared emissivity increases with the increase of STPC on the wavelength between 8.00 microm and 13 microm, and the emissivity is more sensitive to STPC on the wavelength between 9.00 and 9.6 microm; the estimate mode based on multiple stepwise regression was could not to estimate deserts soil total phosphorus content from thermal-infrared emissivity because the estimation effects of them were poor. The estimation accuracy of model based on partial least squares regression is higher than the model based on multiple stepwise regression. However, the accuracy of second-order differential estimation model based on partial least square regression is higher than based on multiple stepwise regression; The first differential of continuous remove estimation model based on partial least squares regression is the best model with R2 of correction and verification are up to

  16. [Study on quantificational analysis method for the non-crystalline content in blast furnace slag].

    PubMed

    Yan, Ding-Liu; Guo, Pei-Min; Qi, Yuan-Hong; Zhang, Chun-Xia; Wang, Hai-Feng; Dai, Xiao-Tian

    2008-02-01

    Quantificational analysis method for the non-crystalline and crystalline contents in blast furnace slag was studied by means of X-ray diffraction. The process of quantificational analysis method includes standard samples preparation, samples preparation, X-ray diffraction measurement and data treatment. The data treatment includes integration areas of non-crystalline curve and crystalline peaks in certain diffraction angle range, linear fitting and quantificational coefficient determination. The preparation methods of standard samples for X-ray diffraction of blast furnace slag were proposed, including 100% crystalline sample and 100% non-crystalline sample. The 100% crystalline sample can be obtained by heating blast furnace slag for 12 h at 1 000-1 200 degrees C, and the 100% non-crystalline sample can be obtained by quenching the molten slag with enough water. The X-ray diffraction method of quantificational analysis of non-crystalline content in blast furnace slag was proposed with the 100% non-crystalline and 100% crystalline standard samples, and the quantificational coefficient can be obtained by linear regression on the integration areas of non-crystalline curve and crystalline peaks of X-ray diffraction in the 2-theta range 20 degrees-40 degrees. This method is suitable for the blast furnace slag with the non-crystalline content over 80%. The non-crystalline and crystalline contents of original blast furnace slag are obtained by combining the X-ray diffraction results and mathematical treatment, and this method is suitable for the blast furnace slag with the non-crystalline content over 90%, whose process includes preparing the 100% crystalline standard sample by heating blast furnace slag for 12 h at 1000-1200 degrees C, samples preparation with the 0.02 interval in the 0-0.1 mass ratio range of 100% crystalline to original slag, X-ray diffraction measurement of the samples prepared and data treatment using iterative linear regression. The

  17. The Role of CXCR4 and Arrestins in Breast Cancer Signaling and Apoptosis

    DTIC Science & Technology

    2007-02-01

    better understand and treat diseases caused by defects in GPCR trafficking and signaling. 7 BODY Task 1. Adaptor Protein-2 interaction with... treat countless patients affected by diseases that involve dysregulation of GPCR trafficking and signaling. 125 REFERENCES 1. P. Penela et al...latter has not been as thoroughly studied. To better understand the process of GPCR post-endocytic trafficking, we focused on the N-formyl peptide

  18. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content

    PubMed Central

    Smith, Zachary J.; Lee, Changwon; Rojalin, Tatu; Carney, Randy P.; Hazari, Sidhartha; Knudson, Alisha; Lam, Kit; Saari, Heikki; Ibañez, Elisa Lazaro; Viitala, Tapani; Laaksonen, Timo; Yliperttula, Marjo; Wachsmann-Hogiu, Sebastian

    2015-01-01

    Current analysis of exosomes focuses primarily on bulk analysis, where exosome-to-exosome variability cannot be assessed. In this study, we used Raman spectroscopy to study the chemical composition of single exosomes. We measured spectra of individual exosomes from 8 cell lines. Cell-line-averaged spectra varied considerably, reflecting the variation in total exosomal protein, lipid, genetic, and cytosolic content. Unexpectedly, single exosomes isolated from the same cell type also exhibited high spectral variability. Subsequent spectral analysis revealed clustering of single exosomes into 4 distinct groups that were not cell-line specific. Each group contained exosomes from multiple cell lines, and most cell lines had exosomes in multiple groups. The differences between these groups are related to chemical differences primarily due to differing membrane composition. Through a principal components analysis, we identified that the major sources of spectral variation among the exosomes were in cholesterol content, relative expression of phospholipids to cholesterol, and surface protein expression. For example, exosomes derived from cancerous versus non-cancerous cell lines can be largely separated based on their relative expression of cholesterol and phospholipids. We are the first to indicate that exosome subpopulations are shared among cell types, suggesting distributed exosome functionality. The origins of these differences are likely related to the specific role of extracellular vesicle subpopulations in both normal cell function and carcinogenesis, and they may provide diagnostic potential at the single exosome level. PMID:26649679

  19. Some recent studies on groundwater radon content as an earthquake precursor

    SciTech Connect

    Teng, T.

    1980-06-10

    Some recent studies of groundwater radon content in relation to seismic activities are reviewed. Results from China and Japan are presented, including laboratory experients and the development of continuous groundwater radon monitoring systems. In addition, groundwater radon monitoring studies conducted at the University of Southern California (USC) since 1974 are presented in some detail. The USC project includes a groundwater radon monitoring network of 14 sampling sites at cold springs, hot springs, deep irrigation wells, and artesian wells that are distributed along a 'locked' stretch of the San Andreas fault from Gorman to San Bernardino in California. Radon contents in weekly samples from these sites are analyzed to the precision of a few percent. No moderate-to-large earthquake has yet occurred in the vicinity, and the results show no clear association of radon anomalies with small (Mapprox.3) earthquakes to provide better test conditions. In contrast to earlier reports from Russia showing a long-term buildup of radon emission before earthquake occurrence, several recent reports from China and Japan show that groundwater radon anomalies can be short in duration and occur only within a few days before the main shocks. Observation of such effects are made possible with the use of continuous monitoring systems. In general, available data suggest that groundwater radon monitoring could sometimes yield precursor information. However, criteria have yet to be established by which sampling sites and sampling frequencies are selected.

  20. Regional mapping of forest canopy water content and biomass using AIRSAR images over BOREAS study area

    NASA Technical Reports Server (NTRS)

    Saatchi, Sasan; Rignot, Eric; Vanzyl, Jakob

    1995-01-01

    In recent years, monitoring vegetation biomass over various climate zones has become the primary focus of several studies interested in assessing the role of the ecosystem responses to climate change and human activities. Airborne and spaceborne Synthetic Aperture Radar (SAR) systems provide a useful tool to directly estimate biomass due to its sensitivity to structural and moisture characteristics of vegetation canopies. Even though the sensitivity of SAR data to total aboveground biomass has been successfully demonstrated in many controlled experiments over boreal forests and forest plantations, so far, no biomass estimation algorithm has been developed. This is mainly due to the fact that the SAR data, even at lowest frequency (P-band) saturates at biomass levels of about 200 tons/ha, and the structure and moisture information in the SAR signal forces the estimation algorithm to be forest type dependent. In this paper, we discuss the development of a hybrid forest biomass algorithm which uses a SAR derived land cover map in conjunction with a forest backscatter model and an inversion algorithm to estimate forest canopy water content. It is shown that unlike the direct biomass estimation from SAR data, the estimation of water content does not depend on the seasonal and/or environmental conditions. The total aboveground biomass can then be derived from canopy water content for each type of forest by incorporating other ecological information. Preliminary results from this technique over several boreal forest stands indicate that (1) the forest biomass can be estimated with reasonable accuracy, and (2) the saturation level of the SAR signal can be enhanced by separating the crown and trunk biomass in the inversion algorithm. We have used the JPL AIRSAR data over BOREAS southern study area to test the algorithm and to generate regional scale water content and biomass maps. The results are compared with ground data and the sources of errors are discussed. Several SAR

  1. A Candidate-Gene Association Study for Berry Colour and Anthocyanin Content in Vitis vinifera L.

    PubMed Central

    Cardoso, Silvana; Lau, Winston; Eiras Dias, José; Fevereiro, Pedro; Maniatis, Nikolas

    2012-01-01

    Anthocyanin content is a trait of major interest in Vitis vinifera L. These compounds affect grape and wine quality, and have beneficial effects on human health. A candidate-gene approach was used to identify genetic variants associated with anthocyanin content in grape berries. A total of 445 polymorphisms were identified in 5 genes encoding transcription factors and 10 genes involved in either the biosynthetic pathway or transport of anthocyanins. A total of 124 SNPs were selected to examine association with a wide range of phenotypes based on RP-HPLC analysis and visual characterization. The phenotypes were total skin anthocyanin (TSA) concentration but also specific types of anthocyanins and relative abundance. The visual assessment was based on OIV (Organisation Internationale de la Vigne et du Vin) descriptors for berry and skin colour. The genes encoding the transcription factors MYB11, MYBCC and MYCB were significantly associated with TSA concentration. UFGT and MRP were associated with several different types of anthocyanins. Skin and pulp colour were associated with nine genes (MYB11, MYBCC, MYCB, UFGT, MRP, DFR, LDOX, CHI and GST). Pulp colour was associated with a similar group of 11 genes (MYB11, MYBCC, MYCB, MYCA, UFGT, MRP, GST, DFR, LDOX, CHI and CHSA). Statistical interactions were observed between SNPs within the transcription factors MYB11, MYBCC and MYCB. SNPs within LDOX interacted with MYB11 and MYCB, while SNPs within CHI interacted with MYB11 only. Together, these findings suggest the involvement of these genes in anthocyanin content and on the regulation of anthocyanin biosynthesis. This work forms a benchmark for replication and functional studies. PMID:23029369

  2. Outcome Reporting Bias in Government-Sponsored Policy Evaluations: A Qualitative Content Analysis of 13 Studies

    PubMed Central

    2016-01-01

    The reporting of evaluation outcomes can be a point of contention between evaluators and policy-makers when a given reform fails to fulfil its promises. Whereas evaluators are required to report outcomes in full, policy-makers have a vested interest in framing these outcomes in a positive light–especially when they previously expressed a commitment to the reform. The current evidence base is limited to a survey of policy evaluators, a study on reporting bias in education research and several studies investigating the influence of industry sponsorship on the reporting of clinical trials. The objective of this study was twofold. Firstly, it aimed to assess the risk of outcome reporting bias (ORB or ‘spin’) in pilot evaluation reports, using seven indicators developed by clinicians. Secondly, it sought to examine how the government’s commitment to a given reform may affect the level of ORB found in the corresponding evaluation report. To answer these questions, 13 evaluation reports were content-analysed, all of which found a non-significant effect of the intervention on its stated primary outcome. These reports were systematically selected from a dataset of 233 pilot and experimental evaluations spanning three policy areas and 13 years of government-commissioned research in the UK. The results show that the risk of ORB is real. Indeed, all studies reviewed here resorted to at least one of the presentational strategies associated with a risk of spin. This study also found a small, negative association between the seniority of the reform’s champion and the risk of ORB in the evaluation of that reform. The publication of protocols and the use of reporting guidelines are recommended. PMID:27690131

  3. Outcome Reporting Bias in Government-Sponsored Policy Evaluations: A Qualitative Content Analysis of 13 Studies.

    PubMed

    Vaganay, Arnaud

    The reporting of evaluation outcomes can be a point of contention between evaluators and policy-makers when a given reform fails to fulfil its promises. Whereas evaluators are required to report outcomes in full, policy-makers have a vested interest in framing these outcomes in a positive light-especially when they previously expressed a commitment to the reform. The current evidence base is limited to a survey of policy evaluators, a study on reporting bias in education research and several studies investigating the influence of industry sponsorship on the reporting of clinical trials. The objective of this study was twofold. Firstly, it aimed to assess the risk of outcome reporting bias (ORB or 'spin') in pilot evaluation reports, using seven indicators developed by clinicians. Secondly, it sought to examine how the government's commitment to a given reform may affect the level of ORB found in the corresponding evaluation report. To answer these questions, 13 evaluation reports were content-analysed, all of which found a non-significant effect of the intervention on its stated primary outcome. These reports were systematically selected from a dataset of 233 pilot and experimental evaluations spanning three policy areas and 13 years of government-commissioned research in the UK. The results show that the risk of ORB is real. Indeed, all studies reviewed here resorted to at least one of the presentational strategies associated with a risk of spin. This study also found a small, negative association between the seniority of the reform's champion and the risk of ORB in the evaluation of that reform. The publication of protocols and the use of reporting guidelines are recommended.

  4. An Analysis of Social Studies Teachers' Perception Levels Regarding Web Pedagogical Content Knowledge

    ERIC Educational Resources Information Center

    Yesiltas, Erkan

    2016-01-01

    Web pedagogical content knowledge generally takes pedagogical knowledge, content knowledge, and Web knowledge as basis. It is a structure emerging through the interaction of these three components. Content knowledge refers to knowledge of subjects to be taught. Pedagogical knowledge involves knowledge of process, implementation, learning methods,…

  5. Content of Bachelors' in Tourism Informative Training in Ukrainian and Polish Experience: Comparative Study

    ERIC Educational Resources Information Center

    Zubekhina, Tetiana

    2015-01-01

    This article provides a comparative analysis of the content of Bachelors' in Tourism informative training in Ukrainian and Polish experience. The content of Bachelors' in Tourism informative training in Ukraine and Poland has been analyzed. The content of subjects, namely, "Information Technologies in Tourism" and "The Foundations…

  6. The Common Core Writing Standards: A Descriptive Study of Content and Alignment with a Sample of Former State Standards

    ERIC Educational Resources Information Center

    Troia, Gary A.; Olinghouse, Natalie G.; Wilson, Joshua; Stewart, Kelly A.; Mo, Ya; Hawkins, Lisa; Kopke, Rachel A.

    2016-01-01

    Many students do not meet expected standards of writing performance, despite the need for writing competence in and out of school. As policy instruments, writing content standards have an impact on what is taught and how students perform. This study reports findings from an evaluation of the content of a sample of seven diverse states' current…

  7. High pressure experimental study of eclogite with varying H2O contents

    NASA Astrophysics Data System (ADS)

    Rosenthal, A.; Frost, D. J.; Petitgirard, S.; Yaxley, G. M.; Berry, A.; Woodland, A. B.; Pinter, Z.; Vasilyev, P.; Ionov, D. A.; Jacob, D. E.; Pearson, G. D.; Kovacs, I.; Padron-Navarta, A.

    2014-12-01

    Given the strong influence of volatiles on mantle melting processes, it is critical to understand the behaviour of volatiles (such as H2O) in subducted oceanic crustal material (eclogite) during subduction and subsequent recycling and mantle melting processes, and their impacts on volcanism. As natural samples from subduction zones from the deep Earth's interior are largely inaccessible, the only way to determine the H2O content of eclogite is to simulate high pressure (P) and temperature (T) conditions equivalent to conditions of the Earth's interior using high-P experimental facilities. A particular interest is to determine the H2O content of eclogitic nominally anhydrous minerals (NAMs; such as garnet, clinopyroxene) at the conditions where hydrous phases (such as phengite) are breaking down to release H2O that would then leave the slab. As a starting material, we use average oceanic basalt (GA1, representative of recycled oceanic crust [1]) with varying bulk %H2O (≤7 wt.%). We conducted experiments using GA1 at different P's (6-10 GPa), T's (850-1500°C) and bulk %H2O (up to 7 wt.%) using multi anvil apparatuses. The run products at each P, T, and bulk H2O contents show well-equilibrated eclogitic phase assemblages of garnet ± clinopyroxene ± coesite/stishovite ± rutile ± phengite ± melt ± vapour. Runs (>0.5 wt.% H2O) at 6 GPa and up to ~950°C, and at 8-9 GPa and up to ~1050°C are subsolidus, while towards higher T small melt fractions appear. Similar to previous studies [e.g. 2-6], the stability of phengite varies as a function of P, T, buffering mineral paragenesis and bulk H2O concentration. Phengite breaks down >9 GPa. Eclogitic NAMs and phengite also break down at subsolidus conditions in the presence of excess of hydrous fluids. For instance, K2O in phengite and clinopyroxene decrease with increasing bulk H2O content at subsolidus conditions at given P, T, suggesting a leaching role of K2O by a vapour-rich fluid. [1] Yaxley, G. M. & Green, D. H

  8. Studying calcium triggered vesicle fusion in a single vesicle-vesicle content/lipid mixing system

    PubMed Central

    Kyoung, Minjoung; Zhang, Yunxiang; Diao, Jiajie; Chu, Steven; Brunger, Axel T.

    2013-01-01

    This Protocol describes a single vesicle-vesicle microscopy system to study Ca2+-triggered vesicle fusion. Donor vesicles contain reconstituted synaptobrevin and synaptotagmin-1. Acceptor vesicles contain reconstituted syntaxin and SNAP-25, and are tethered to a PEG-coated glass surface. Donor vesicles are mixed with the tethered acceptor vesicles and incubated for several minutes at zero Ca2+-concentration, resulting in a collection of single interacting vesicle pairs. The donor vesicles also contain two spectrally distinct fluorophores that allow simultaneous monitoring of temporal changes of the content and membrane. Upon Ca2+-injection into the sample chamber, our system therefore differentiates between hemifusion and complete fusion of interacting vesicle pairs and determines the temporal sequence of these events on a sub-hundred millisecond timescale. Other factors, such as complexin, can be easily added. Our system is unique by monitoring both content and lipid mixing, and by starting from a metastable state of interacting vesicle pairs prior to Ca2+-injection. PMID:23222454

  9. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality.

  10. Ludic content in multisensory stimulation environments: an exploratory study about practice in Portugal.

    PubMed

    Castelhano, Nuno; Silva, Fabiana; Rezende, Márcia; Roque, Licínio; Magalhães, Lívia

    2013-09-01

    This article aims to document the use of multisensory stimulation environments and its related perceptions, concerning ludic content, play and the computer-mediated ludic activity, from the perspective of professionals organizing and delivering therapeutic activities in these spaces with children with developmental disabilities, in Portugal. Face-to-face open interviews with 12 professionals working in multisensory stimulation environments, selected by convenience criteria, were individually recorded, transcribed and submitted to content analysis. Three main themes emerged from the data: multisensory stimulation environments offer multiple possibilities for intervention, play is part of the intervention in multisensory environments and the computer-mediated ludic experience is perceived as useful for intervention. Data suggest that multisensory stimulation environments are used as versatile spaces, both considered and explored by the interviewed professionals in its ludic potential. This fact can renew the interest in multisensory environments, in particular for the area of play in Occupational Therapy, in which the use of the computer-mediated ludic experience is a recognized possibility. Limitations of this study are associated to the level of representativeness of the interviews in relation to the diverse universe of professionals using multisensory environments. The method for collecting data is also highly sensitive to the influence of the interviewer.

  11. Specific α-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2.

    PubMed

    Alvaro, Christopher G; O'Donnell, Allyson F; Prosser, Derek C; Augustine, Andrew A; Goldman, Aaron; Brodsky, Jeffrey L; Cyert, Martha S; Wendland, Beverly; Thorner, Jeremy

    2014-07-01

    G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate responses to extracellular stimuli by mediating ligand-dependent activation of cognate heterotrimeric G proteins. In yeast, occupancy of GPCR Ste2 by peptide pheromone α-factor initiates signaling by releasing a stimulatory Gβγ complex (Ste4-Ste18) from its inhibitory Gα subunit (Gpa1). Prolonged pathway stimulation is detrimental, and feedback mechanisms have evolved that act at the receptor level to limit the duration of signaling and stimulate recovery from pheromone-induced G1 arrest, including upregulation of the expression of an α-factor-degrading protease (Bar1), a regulator of G-protein signaling protein (Sst2) that stimulates Gpa1-GTP hydrolysis, and Gpa1 itself. Ste2 is also downregulated by endocytosis, both constitutive and ligand induced. Ste2 internalization requires its phosphorylation and subsequent ubiquitinylation by membrane-localized protein kinases (Yck1 and Yck2) and a ubiquitin ligase (Rsp5). Here, we demonstrate that three different members of the α-arrestin family (Ldb19/Art1, Rod1/Art4, and Rog3/Art7) contribute to Ste2 desensitization and internalization, and they do so by discrete mechanisms. We provide genetic and biochemical evidence that Ldb19 and Rod1 recruit Rsp5 to Ste2 via PPXY motifs in their C-terminal regions; in contrast, the arrestin fold domain at the N terminus of Rog3 is sufficient to promote adaptation. Finally, we show that Rod1 function requires calcineurin-dependent dephosphorylation.

  12. Assessment study of insight ARTHRO VR (®) arthroscopy virtual training simulator: face, content, and construct validities.

    PubMed

    Bayona, Sofía; Fernández-Arroyo, José Manuel; Martín, Isaac; Bayona, Pilar

    2008-09-01

    The aims of this study were to test the face, content, and construct validities of a virtual-reality haptic arthroscopy simulator and to validate four assessment hypothesis. The participants in our study were 94 arthroscopists attending an international conference on arthroscopy. The interviewed surgeons had been performing arthroscopies for a mean of 8.71 years (σ = 6.94 years). We explained the operation, functionality, instructions for use, and the exercises provided by the simulator. They performed a trial exercise and then an exercise in which performance was recorded. After having using it, the arthroscopists answered a questionnaire. The simulator was classified as one of the best training methods (over phantoms), and obtained a mark of 7.10 out of 10 as an evaluation tool. The simulator was considered more useful for inexperienced surgeons than for surgeons with experience (mean difference 1.88 out of 10, P value < 0.001). The participants valued the simulator at 8.24 as a tool for learning skills, its fidelity at 7.41, the quality of the platform at 7.54, and the content of the exercises at 7.09. It obtained a global score of 7.82. Of the subjects, 30.8% said they would practise with the simulator more than 6 h per week. Of the surgeons, 89.4% affirmed that they would recommend the simulator to their colleagues. The data gathered support the first three hypotheses, as well as face and content validities. Results show statistically significant differences between experts and novices, thus supporting the construct validity, but studies with a larger sample must be carried out to verify this. We propose concrete solutions and an equation to calculate economy of movement. Analogously, we analyze competence measurements and propose an equation to provide a single measurement that contains them all and that, according to the surgeons' criteria, is as reliable as the judgment of experts observing the performance of an apprentice.

  13. How have researchers studied multiracial populations: A content and methodological review of 20 years of research

    PubMed Central

    Charmaraman, Linda; Woo, Meghan; Quach, Ashley; Erkut, Sumru

    2014-01-01

    The U. S. Census shows that the racial-ethnic make-up of over 9 million people (2.9% of the total population) who self-identified as multiracial is extremely diverse. Each multiracial subgroup has unique social and political histories that may lead to distinct societal perceptions, economic situations, and health outcomes. Despite the increasing academic and media interest in multiracial individuals, there are methodological and definitional challenges in studying the population resulting in conflicting representations in the literature. This content and methods review of articles on multiracial populations provides a comprehensive understanding of which multiracial populations have been included in research and how they have been studied both to recognize the emerging research and to identify gaps for guiding future research on this complex but increasingly visible population. We examine 125 U.S.-based peer-reviewed journal articles published over the past 20 years (1990–2009) containing 133 separate studies focused on multiracial individuals from primarily the fields of psychology, sociology, social work, education, and public health. Findings include (a) descriptive data regarding the sampling strategies, methodologies, and demographic characteristics of studies, including which multiracial subgroups are most studied, gender, age range, region of country, socioeconomic status; (b) major thematic trends in research topics concerning multiracial populations; (c) implications and recommendations for future studies. PMID:25045946

  14. Study on reflection coefficient of clayey material focusing on smectite content and partial density

    NASA Astrophysics Data System (ADS)

    Miyoshi, S.; Tokunaga, T.; Mogi, K.

    2009-12-01

    1.Introduction Geologic clayey material can work as semipermeable membrane because migration of anion in pore solution is restricted by the clay surface charge (Ingebritsen et al., 2006). Kemper and Evans (1963) showed that the flow rate of chemically-driven flow is proportional to the gradient of chemical potential and that the proportionality constant is the product of permeability and reflection coefficient. Bresler (1973) delivered a reflection coefficient function of the conductive film thickness (2b) and the concentration of outer solution (C), which is called Bresler's Curve. In the study, the reflection coefficient calculated by using the apparent value of b based on the observed permeability was consistent with the value obtained by the laboratory experiments using the clay pastes with high water content, while the reflection coefficient calculated by using averaged b was not. Bresler described the reason that there were macro-pores in the clay pastes with high water content. In this study, chemical osmosis of highly-compacted bentonite was observed by using laboratory apparatus. The reason for the use of compacted bentonite is that monmorillonite content and partial density is obvious. Then numerical simulation of the experiment was done considering the effect of monmorillonite content and partial density. 2. Results and discussion Kunigeru V1 (Kunimine Co. Ltd.) is a bentonite product involving approximately fifty percent weight Na-type monmorillonite. In the compacted Kunigeru V1 whose dry density is 1.2Mg/m3, monmorillonite partial density is 0.78Mg/m3. According to Torigai (1996), in the compacted almost pure Na-type monmorillonite whose dry density is 0.80Mg/m3, monmorillonite has homogeneously three water molecule swelling layers and the interval of its platelet is approximately 1.9nm. According to Bresler's Curve, reflection coefficient is 1.0 when 2b is equal to 1.9nm and the concentration of outer sodium chloride solution is equal to or less than

  15. Study on fast measurement of sugar content of yogurt using Vis/NIR spectroscopy techniques

    NASA Astrophysics Data System (ADS)

    He, Yong; Feng, Shuijuan; Wu, Di; Li, Xiaoli

    2006-09-01

    In order to measuring the sugar content of yogurt rapidly, a fast measurement of sugar content of yogurt using Vis/NIR-spectroscopy techniques was established. 25 samples selected separately from five different brands of yogurt were measured by Vis/NIR-spectroscopy. The sugar content of yogurt on positions scanned by spectrum were measured by a sugar content meter. The mathematical model between sugar content and Vis/NIR spectral measurements was established and developed based on partial least squares (PLS). The correlation coefficient of sugar content based on PLS model is more than 0.894, and standard error of calibration (SEC) is 0.356, standard error of prediction (SEP) is 0.389. Through predicting the sugar content quantitatively of 35 samples of yogurt from 5 different brands, the correlation coefficient between predictive value and measured value of those samples is more than 0.934. The results show the good to excellent prediction performance. The Vis/NIR spectroscopy technique had significantly greater accuracy for determining the sugar content. It was concluded that the Vis/NIRS measurement technique seems reliable to assess the fast measurement of sugar content of yogurt, and a new method for the measurement of sugar content of yogurt was established.

  16. Pressure ulcer prevention algorithm content validation: a mixed-methods, quantitative study.

    PubMed

    van Rijswijk, Lia; Beitz, Janice M

    2015-04-01

    Translating pressure ulcer prevention (PUP) evidence-based recommendations into practice remains challenging for a variety of reasons, including the perceived quality, validity, and usability of the research or the guideline itself. Following the development and face validation testing of an evidence-based PUP algorithm, additional stakeholder input and testing were needed. Using convenience sampling methods, wound care experts attending a national wound care conference and a regional wound ostomy continence nursing (WOCN) conference and/or graduates of a WOCN program were invited to participate in an Internal Review Board-approved, mixed-methods quantitative survey with qualitative components to examine algorithm content validity. After participants provided written informed consent, demographic variables were collected and participants were asked to comment on and rate the relevance and appropriateness of each of the 26 algorithm decision points/steps using standard content validation study procedures. All responses were anonymous. Descriptive summary statistics, mean relevance/appropriateness scores, and the content validity index (CVI) were calculated. Qualitative comments were transcribed and thematically analyzed. Of the 553 wound care experts invited, 79 (average age 52.9 years, SD 10.1; range 23-73) consented to participate and completed the study (a response rate of 14%). Most (67, 85%) were female, registered (49, 62%) or advanced practice (12, 15%) nurses, and had > 10 years of health care experience (88, 92%). Other health disciplines included medical doctors, physical therapists, nurse practitioners, and certified nurse specialists. Almost all had received formal wound care education (75, 95%). On a Likert-type scale of 1 (not relevant/appropriate) to 4 (very relevant and appropriate), the average score for the entire algorithm/all decision points (N = 1,912) was 3.72 with an overall CVI of 0.94 (out of 1). The only decision point/step recommendation

  17. A new high-content model system for studies of gastrointestinal transit: the zebrafish.

    PubMed

    Rich, A

    2009-03-01

    The zebrafish gastrointestinal (GI) tract displays an anatomy and cellular architecture that is similar to the human GI tract, with concentric layers of inner epithelia, connective tissue, circular muscle and outer longitudinal muscle layers. Propulsion of luminal content results from the integrated activity of smooth muscle cells, enteric neurons and the interstitial cells of Cajal (ICC). Zebrafish larvae are transparent and propagating contractions in the entire GI tract are easily visualized. A new moderate-throughput zebrafish-based GI transit assay is described in this issue of Neurogastroenterology and Motility. This assay utilizes intact zebrafish larvae which contain essential regulatory elements (ICC and enteric neurons). Forward genetic analysis, which identifies genes underlying specific phenotypes, is possible using the zebrafish system. The zebrafish model system compliments existing models for studies of GI motility and will contribute to the understanding of the regulation of GI motility, and to identification of novel drug targets.

  18. Studies of Genetic Variation of Essential Oil and Alkaloid Content in Boldo (Peumus boldus).

    PubMed

    Vogel, H; Razmilic, I; Muñoz, M; Doll, U; Martin, J S

    1999-02-01

    Boldo is a tree or shrub with medicinal properties native to Chile. The leaves contain alkaloids and essential oils. Variation of total alkaloid concentration, of the alkaloid boldine, and essential oil components were studied in different populations from northern, central, and southern parts of its geographic range and in their progenies (half-sib families). Total alkaloid concentration showed genetic variation between progenies of the central population but not between populations. Boldine content found in concentrations of 0.007 to 0.009% did not differ significantly between populations. Principal components of the essential oil were determined genetically, with highest values for ascaridole in the population of the north and for P-cymene in the south. Between half-sib families genetic variation was found in the central and northern populations for these components. The high heritability coefficients found indicate considerable potential for successful selection of individuals for these characters.

  19. Content management systems and E-commerce: a comparative case study

    NASA Astrophysics Data System (ADS)

    Al Rasheed, Amal A.; El-Masri, Samir D.

    2011-12-01

    The need for CMS's to create and edit e-commerce websites has increased with the growing importance of e-commerce. In this paper, the various features essential for e-commerce CMS's are explored. The aim of the paper was to find the best CMS solution for e-commerce which includes the best of both CMS and store management. Accordingly, we conducted a study on three popular open source CMS's for e-commerce: VirtueMart from Joomla!, Ubercart from Drupal, and Magento. We took into account features like hosting and installation, performance, support/community, content management, add on modules and functional features. We concluded with improvements that could be made in order to alleviate problems.

  20. Study of the heavy flavor content of jets produced in W events at the Tevatron collider

    SciTech Connect

    G. Apollinari

    2002-08-01

    We present a detailed study of the heavy flavor content in the W + jet data sample collected with the CDF detector during the 1992-1995 collider run at Fermilab. Rates of heavy flavor jets, identified via the observation of secondary vertices or semileptonic decays of b and c quarks, are in good agreement with a standard model simulation including production of the top quark. An exception is the number of events in which a single jet has both a secondary vertex and a semileptonic decay tag. In the W + 2,3 jet data, we expect 4.4 {+-} 0.6 and we find 13 such events. The kinematic properties of this small sample of events are statistically difficult to reconcile with the simulation of standard model processes.

  1. Studies on the pH value of abomasal contents in dairy cows during the first 3 weeks after calving.

    PubMed

    Van Winden, S C L; Müller, K E; Kuiper, R; Noordhuizen, J P T M

    2002-04-01

    The pH value of the abomasal contents in adult cattle is normally constant and has a value of 2. Abomasal contents with pH values of 5.5 and higher could give rise to bacterial fermentation with subsequent gas production. The accumulation of gas is thought to form a key event in the pathogenesis of abomasal displacement. The aim of the present study was to determine the pH values of abomasal contents of dairy cows in the first 3 weeks after calving. The pH of the abomasal contents was, over several days. higher than the pH value of the abomasal juice in mid-lactation cows. The highest pH values were measured on day 14 after calving, thereafter the pH declined. Possible explanations for the rise in the pH value of the abomasal contents are discussed.

  2. Socialization Content in Schools and Education for Sustainable Development--II. A Study of Students' Apprehension of Teachers' Companion Meanings in ESD

    ERIC Educational Resources Information Center

    Sund, Per; Wickman, Per-Olof

    2011-01-01

    Subject content is always studied within an educational context. This context is constituted by the socialization content, which can be regarded as an educational content beyond the subject content. This is the third article of three studies (this article; Sund and Wickman 2011; Sund 2008) that together form a triangulation of possible…

  3. Instructional Developer as Content Specialist: Three Case Studies Utilizing the Instructional Development-Operations Research Model.

    ERIC Educational Resources Information Center

    Faust, Stephen M.

    1980-01-01

    Presents a 3-phase model (content research, specification, delivery) for instructional development-operations research and describes its application in developing courses in zoology, geology, and paleontology. (MER)

  4. Using measured soil water contents to estimate evapotranspiration and root water uptake profiles - a comparative study

    NASA Astrophysics Data System (ADS)

    Guderle, M.; Hildebrandt, A.

    2015-01-01

    Understanding the role of plants in soil water relations, and thus ecosystem functioning, requires information about root water uptake. We evaluated four different complex water balance methods to estimate sink term patterns and evapotranspiration directly from soil moisture measurements. We tested four methods. The first two take the difference between two measurement intervals as evapotranspiration, thus neglecting vertical flow. The third uses regression on the soil water content time series and differences between day and night to account for vertical flow. The fourth accounts for vertical flow using a numerical model and iteratively solves for the sink term. None of these methods requires any a priori information of root distribution parameters or evapotranspiration, which is an advantage compared to common root water uptake models. To test the methods, a synthetic experiment with numerical simulations for a grassland ecosystem was conducted. Additionally, the time series were perturbed to simulate common sensor errors, like those due to measurement precision and inaccurate sensor calibration. We tested each method for a range of measurement frequencies and applied performance criteria to evaluate the suitability of each method. In general, we show that methods accounting for vertical flow predict evapotranspiration and the sink term distribution more accurately than the simpler approaches. Under consideration of possible measurement uncertainties, the method based on regression and differentiating between day and night cycles leads to the best and most robust estimation of sink term patterns. It is thus an alternative to more complex inverse numerical methods. This study demonstrates that highly resolved (temporally and spatially) soil water content measurements may be used to estimate the sink term profiles when the appropriate approach is used.

  5. Informing Estimates of Program Effects for Studies of Mathematics Professional Development Using Teacher Content Knowledge Outcomes.

    PubMed

    Phelps, Geoffrey; Kelcey, Benjamin; Jones, Nathan; Liu, Shuangshuang

    2016-10-03

    Mathematics professional development is widely offered, typically with the goal of improving teachers' content knowledge, the quality of teaching, and ultimately students' achievement. Recently, new assessments focused on mathematical knowledge for teaching (MKT) have been developed to assist in the evaluation and improvement of mathematics professional development. This study presents empirical estimates of average program change in MKT and its variation with the goal of supporting the design of experimental trials that are adequately powered to detect a specified program effect. The study drew on a large database representing five different assessments of MKT and collectively 326 professional development programs and 9,365 teachers. Results from cross-classified hierarchical growth models found that standardized average change estimates across the five assessments ranged from a low of 0.16 standard deviations (SDs) to a high of 0.26 SDs. Power analyses using the estimated pre- and posttest change estimates indicated that hundreds of teachers are needed to detect changes in knowledge at the lower end of the distribution. Even studies powered to detect effects at the higher end of the distribution will require substantial resources to conduct rigorous experimental trials. Empirical benchmarks that describe average program change and its variation provide a useful preliminary resource for interpreting the relative magnitude of effect sizes associated with professional development programs and for designing adequately powered trials.

  6. Technical Communications in OSS Content Management Systems: An Academic Institutional Case Study

    ERIC Educational Resources Information Center

    Cripps, Michael J.

    2011-01-01

    Single sourcing through a content management system (CMS) is altering technical communication practices in many organizations, including institutions of higher education. Open source software (OSS) solutions are currently among the most popular content management platforms adopted by colleges and universities in the United States and abroad. The…

  7. Pedagogical Content Knowledge and the Gas Laws: A Multiple Case Study

    ERIC Educational Resources Information Center

    Sande, Mary Elizabeth

    2010-01-01

    Pedagogical content knowledge (PCK) has been described as an assemblage of the most powerful analogies, demonstrations, examples and illustrations that make content knowledge understandable to students, together with an understanding of the preconceptions and alternate conceptions that students bring with them to the classroom (Shulman, 1986). In…

  8. Moral Dilemmas/Value Sheets: Writing for Content-Centered Social Studies Classrooms.

    ERIC Educational Resources Information Center

    Stahl, Robert J.; And Others

    The purpose of the paper is to stress the development of content-centered classroom activities useful for attaining values clarification and/or moral development goals. The objective is to help teachers understand the formulation of content-centered learning activities so that they will be able to plan and produce their own value sheets or moral…

  9. Investigating Correspondence between Language Proficiency Standards and Academic Content Standards: A Generalizability Theory Study

    ERIC Educational Resources Information Center

    Lin, Chih-Kai; Zhang, Jinming

    2014-01-01

    Research on the relationship between English language proficiency standards and academic content standards serves to provide information about the extent to which English language learners (ELLs) are expected to encounter academic language use that facilitates their content learning, such as in mathematics and science. Standards-to-standards…

  10. An Experimental Study on the Iso-Content-Based Angle Similarity Measure.

    ERIC Educational Resources Information Center

    Zhang, Jin; Rasmussen, Edie M.

    2002-01-01

    Retrieval performance of the iso-content-based angle similarity measure within the angle, distance, conjunction, disjunction, and ellipse retrieval models is compared with retrieval performance of the distance similarity measure and the angle similarity measure. Results show the iso-content-based angle similarity measure achieves satisfactory…

  11. Sharing Time in Kindergarten: A Study of the Relationship between Structure and Content.

    ERIC Educational Resources Information Center

    Lazarus, Peggy; Homer, Susan L.

    Two sessions of a kindergarten show and tell (spaced 18 days apart) were observed to compare the participant structure and the content of this shared time. Participant structure was examined in terms of turn taking, spatial arrangement, and teacher management of the event. Content was analyzed in terms of topic and cognitive level. The changes in…

  12. A Learning Content Authoring Approach Based on Semantic Technologies and Social Networking: An Empirical Study

    ERIC Educational Resources Information Center

    Nesic, Sasa; Gasevic, Dragan; Jazayeri, Mehdi; Landoni, Monica

    2011-01-01

    Semantic web technologies have been applied to many aspects of learning content authoring including semantic annotation, semantic search, dynamic assembly, and personalization of learning content. At the same time, social networking services have started to play an important role in the authoring process by supporting authors' collaborative…

  13. Fathers’ Representation in Observational Studies on Parenting and Childhood Obesity: A Systematic Review and Content Analysis

    PubMed Central

    Gicevic, Selma; Aftosmes-Tobio, Alyssa; Ganter, Claudia; Simon, Christine L.; Newlan, Sami; Manganello, Jennifer A.

    2016-01-01

    Background. The involvement of fathers in caregiving has increased substantially over the past 30 years. Yet in child and adolescent psychopathology, few studies include fathers as research participants and few present results for fathers separate from those for mothers. We test for the first time whether a similar pattern exists in research on parenting and childhood obesity. Objectives. To conduct a systematic review and quantitative content analysis of observational studies on parenting and childhood obesity to (1) document the inclusion of fathers, relative to mothers, as research participants and (2) examine characteristics of studies that did and did not include fathers. This study presents new data on the number and gender of parent research participants. Search methods. We searched title, abstract, and Medical Subject Headings term fields in 5 research databases (PubMed, EMBASE, Academic Search Premier, PsycINFO, and CINAHL) using terms combining parents or parenting (e.g., mother, father, caregiver, parenting style, food parenting) and obesity (e.g., obesity, body weight, overweight) or obesity-related lifestyle behaviors (e.g., diet, snacking, physical activity, outdoor play, exercise, media use). Selection criteria. We identified and screened studies as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) published between January 2009 and December 2015, examining links between parenting and childhood obesity, including parents or caregivers as research participants, and written in English. We excluded interventions, nonhuman studies, dissertations, conference abstracts, and studies on youths with specific medical conditions. Of 5557 unique studies, 667 studies were eligible. Data collection and analysis. For each of the 667 studies, 4 coders were trained to code characteristics of the study (e.g., publication year, geographic region, journal, study focus) and parent research participants (e.g., parent gender, demographic

  14. An electrophysiological study on the interaction between emotional content and spatial frequency of visual stimuli.

    PubMed

    Carretié, Luis; Hinojosa, José A; López-Martín, Sara; Tapia, Manuel

    2007-03-25

    Previous studies suggest that the magnocellular pathway, a visual processing system that rapidly provides low spatial frequency information to fast-responding structures such as the amygdala, is more involved in the processing of emotional facial expressions than the parvocellular pathway (which conveys all spatial frequencies). The present experiment explored the spatio-temporal characteristics of the spatial frequency modulation of affect-related neural processing, as well as its generalizability to non-facial stimuli. To that aim, the event-related potentials (ERPs) elicited by low-pass filtered (i.e., high spatial frequencies are eliminated) and intact non-facial emotional images were recorded from 31 participants using a 60-electrode array. The earliest significant effect of spatial frequency was observed at 135 ms from stimulus onset: N135 component of the ERPs. In line with previous studies, the origin of N135 was localized at secondary visual areas for low-pass filtered stimuli and at primary areas for intact stimuli. Importantly, this component showed an interaction between spatial frequency and emotional content: within low-pass filtered pictures, negative stimuli elicited the highest N135 amplitudes. By contrast, within intact stimuli, neutral pictures were those eliciting the highest amplitudes. These results suggest that high spatial frequencies are not essential for the initial affect-related processing of visual stimuli, which would mainly rely on low spatial frequency visual information. According to present data, high spatial frequencies would come into play later on.

  15. Measurement of moisture content in photovoltaic panel encapsulants using spectroscopic optical coherence tomography: a feasibility study

    NASA Astrophysics Data System (ADS)

    Rashtchi, Shabnam; Ruiz, Pablo D.; Wildman, Ricky; Ashcroft, Ian

    2012-10-01

    EVA, a copolymer of ethylene and vinyl acetate, is a common encapsulant material used in silicon-based PV modules. It contributes to the structural integrity of the modules, provides electrical insulation and also acts as an environmental barrier. However, water can diffuse through EVA into the modules, leading to swelling and chemical degradation, which can impact interfacial bonds, leading to delamination and allowing more ingress to occur that can eventually end up in accelerated corrosion and device failure. Fourier Transform infrared spectroscopy (FTIR) and gravimetric techniques have been used to quantify water concentration and the diffusion coefficient in free standing EVA films. However, these techniques cannot be applied to measure water content in PV modules deployed in the field, as the encapsulant is usually between a glass front sheet and a back sheet made of glass or multilayered films. In this paper we study the feasibility of combining FTIR and spectroscopic optical coherence tomography (SOCT) to measure water concentration of the EVA layer inside the modules. SOCT provides depth resolved spectral information and thus has the potential of measuring water absorption at different layers in the PV module. These depth-resolved measurements are necessary to inform predictive models developed to study the structural integrity, stability and durability of PV modules. The fundamental principle of the technique is explained, the optimum spectral ranges are identified and the feasibility of a SOCT system is discussed based on light source and detector characteristics. Other strategies are also considered.

  16. Comparative studies on the immunoregulatory effects of three polysaccharides using high content imaging system.

    PubMed

    Lv, Xiaocheng; Chen, Dandan; Yang, Liecheng; Zhu, Ning; Li, Jingling; Zhao, Jian; Hu, Zhibi; Wang, Fu-Jun; Zhang, Leshuai W

    2016-05-01

    In this study, polysaccharides were isolated from Astragalus membranaceus, Ganoderma lucidum and Radix ophiopogonis and named APSII, GLPII and OGPII for comparison of their immunoactivities. MTT assay indicated that these polysaccharides increased the metabolic activity of Raw264.7 macrophages and induced cell differentiation to dendritic like cells. High content screening and mathematical modeling were used to quantify the cell irregularity, a hallmark of cell differentiation by polysaccharides. The results showed that GLPII increased cell irregularity, but APSII and OGPII had slightly less effects. Imaging analysis also revealed that polysaccharides inhibited cell proliferation while inducing the cell differentiation. In addition, APSII and GLPII but not OGPII induced NO production and enhanced cell phagocytic ability. Interestingly, inducible nitric oxide synthase inhibitor blocked polysaccharide-enhanced phagocytosis, indicating NO production is crucial for macrophages to acquire phagocytic ability, which was further confirmed by correlation studies. APSII and GLPII significantly promoted the maturation of macrophages by the increase in the expression of MHCII, CD40, CD80 and CD86, while OGPII had less effects. In summary, we have suggested a practical and economical method to quantify macrophage differentiation (irregularity) induced by polysaccharides for quality assurance and have found the role of NO production on macrophage phagocytic ability.

  17. Developing Content Knowledge for Teaching Assessments for the Measures of Effective Teaching Study. Research Report. ETS RR-14-33

    ERIC Educational Resources Information Center

    Phelps, Geoffrey; Weren, Barbara; Croft, Andrew; Gitomer, Drew

    2014-01-01

    This report documents the development of assessments of content knowledge for teaching (CKT) as part of the Measures of Effective Teaching (MET) study, funded by the Bill and Melinda Gates Foundation.The MET study was designed to develop a set of measures that together serve as an accurate indicator of teaching effectiveness. The study was…

  18. Trends in Studies on Virtual Learning Environments in Turkey between 1996-2014 Years: A Content Analysis

    ERIC Educational Resources Information Center

    Demirer, Veysel; Erbas, Cagdas

    2016-01-01

    This study aims to review studies on virtual learning environments in Turkey through the content analysis method. 63 studies consisting of thesis, articles and proceedings published in Turkish and English between 1996-2014 years were analyzed. It was observed that "Second Life" was mostly preferred as the virtual learning environment.…

  19. [Study of contents of nitrates, fluorides, aluminium in dialysis water in Tunisia].

    PubMed

    Jennen, Faycal; Gorbel, Hayette; Hmida, Jalel; Cherni, Noureddine; Abderrazek, Hedhili

    2005-12-01

    Nitrates, fluorides and aluminum have often been incriminated in cases of poisoning sometimes life threatening such as methaemoglobinaemia, dental and skeletal fluorosis, and myoclonal encephalopathy in patients undergoing haemodialysis. The three elements mentioned have something in common: their water origin (drinking water and dialysis water). To study the situation in Tunisia in this respect we propose to determinate the contents of nitrates, fluorides, and aluminum in drinking water and dialysis water supplied by the water board (SONEDE). 540 samples of drinking water and dialysis water were taken from 95 centers of haemodialysis scattered all over the country, between January 2000 and December 2001. These samples are divided in three parts (drinking water, soften water, and dialysis water ). Results show levels of fluorides < 1.5 ppm in most areas with the exception of zones rich in phosphate where the mean level is 1.61 +/- 1.22. the levels of nitrates are in most regions < 50mg/l and those of aluminum < 100microg/l. The levels of fluorides, nitrates and aluminum in dialysis water were within acceptable national and international limits excepting a few centers where the levels of the these contaminants are high, exposing patients on haemodialysis to acute and chronic intoxication. This contamination is caused in majority of cases by a dysfunction of water dialysis treatment chain, therefore caution is necessary and strict measures of control should be introduced.

  20. Health disparities and advertising content of women's magazines: a cross-sectional study

    PubMed Central

    Duerksen, Susan C; Mikail, Amy; Tom, Laura; Patton, Annie; Lopez, Janina; Amador, Xavier; Vargas, Reynaldo; Victorio, Maria; Kustin, Brenda; Sadler, Georgia Robins

    2005-01-01

    Background Disparities in health status among ethnic groups favor the Caucasian population in the United States on almost all major indicators. Disparities in exposure to health-related mass media messages may be among the environmental factors contributing to the racial and ethnic imbalance in health outcomes. This study evaluated whether variations exist in health-related advertisements and health promotion cues among lay magazines catering to Hispanic, African American and Caucasian women. Methods Relative and absolute assessments of all health-related advertising in 12 women's magazines over a three-month period were compared. The four highest circulating, general interest magazines oriented to Black women and to Hispanic women were compared to the four highest-circulating magazines aimed at a mainstream, predominantly White readership. Data were collected and analyzed in 2002 and 2003. Results Compared to readers of mainstream magazines, readers of African American and Hispanic magazines were exposed to proportionally fewer health-promoting advertisements and more health-diminishing advertisements. Photographs of African American role models were more often used to advertise products with negative health impact than positive health impact, while the reverse was true of Caucasian role models in the mainstream magazines. Conclusion To the extent that individual levels of health education and awareness can be influenced by advertising, variations in the quantity and content of health-related information among magazines read by different ethnic groups may contribute to racial disparities in health behaviors and health status. PMID:16109157

  1. Iranian nurses’ perception of spirituality and spiritual care: a qualitative content analysis study

    PubMed Central

    Mahmoodishan, Gholamreza; Alhani, Fatemeh; Ahmadi, Fazlollah; Kazemnejad, Anoshirvan

    2010-01-01

    The purpose of the present study was to explore nurses’ perception about spirituality and spiritual care. A qualitative content analysis approach was conducted on 20 registered nurses interviewed using unstructured strategy in 2009. Three themes emerged from the data analysis: 1) “meaning and purpose of work and life” including ‘spiritualistic view to profession’, ‘commitment and professional responsibility’, and ‘positive attitude’; 2) “religious attitude” including ‘God approval’, ‘spiritual reward’, ‘taking advice’, ‘inner belief in the Supreme Being’, ‘faith-based interactions and altruism’; 3) “transcendence-seeking” including ‘need for respect’ and ‘personal–professional transcendence’. Therefore, the spirituality produces maintenance, harmony and balance in nurses in relation to God. Spiritual care focuses on respecting patients, friendly and sympathetic interactions, sharing in rituals and strengthening patients and nurses’ inner energy. This type of spirituality gives a positive perspective to life and profession, peaceful interactions, a harmonious state of mind, and acts as a motivator among nurses to promote nursing care and spirituality. PMID:23908741

  2. Effects of negative content on the processing of gender information: an event-related potential study.

    PubMed

    Hinojosa, José A; Albert, Jacobo; Fernández-Folgueiras, Uxía; Santaniello, Gerardo; López-Bachiller, Cristina; Sebastián, Manuel; Sánchez-Carmona, Alberto J; Pozo, Miguel A

    2014-12-01

    Previous research on emotion in language has mainly concerned the impact of emotional information on several aspects of lexico-semantic analyses of single words. However, affective influences on morphosyntactic processing are less understood. In the present study, we focused on the impact of negative valence in the processing of gender agreement relations. Event-related potentials (ERPs) were recorded while participants read three-word phrases and performed a syntactic judgment task. Negative and neutral adjectives could agree or disagree in gender with the preceding noun. At an electrophysiological level, the amplitude of a left anterior negativity (LAN) to gender agreement mismatches decreased in negative words, relative to neutral words. The behavioral data suggested that LAN amplitudes might be indexing the processing costs associated with the detection of gender agreement errors, since the detection of gender mismatches resulted in faster and more accurate responses than did the detection of correct gender agreement relations. According to this view, it seems that negative content facilitated the processes implicated in the early detection of gender agreement mismatches. However, gender agreement violations in negative words triggered processes involved in the reanalysis and repair of the syntactic structure, as reflected in larger P600 amplitudes to incorrect than to correct phrases, irrespective of their emotional valence.

  3. A prospective study of the clinical content of palliative medicine interdisciplinary team meetings.

    PubMed

    Powazki, Ruth D; Walsh, Declan; Shrotriya, Shiva

    2015-12-01

    Structured interprofessional communication should improve the structure and clarity of the plan of care. The interdisciplinary team meeting (IDTM) is an opportunity for shared information on patients' and family care needs. We report a prospective observations study of palliative medicine IDTM, which recorded the clinical issues discussed. One hundred and forty-five disparate clinical items were identified for 59 patients and were discussed by the IDTM in about 240 minutes. By content analysis and research meeting consensus, they were grouped into 9 agreed interdisciplinary themes. The 9 themes were then subjected to biostatistical analysis and 3 communication clusters identified. Themes consisted of 3 major communication clusters: (1) clinical services, (2) psychosocial, and (3) care plan. Two themes (information exchange and clinical transitions) did not cluster. The IDTM identified patient care need, reported concerns, and supported collaboration in proactive patient care plans. Future research projects with more patients and a large number of meetings can confirm our findings. This should also examine specific contributions by professional discipline.

  4. Non-invasive quantification of small bowel water content by MRI: a validation study

    NASA Astrophysics Data System (ADS)

    Hoad, C. L.; Marciani, L.; Foley, S.; Totman, J. J.; Wright, J.; Bush, D.; Cox, E. F.; Campbell, E.; Spiller, R. C.; Gowland, P. A.

    2007-12-01

    Substantial water fluxes across the small intestine occur during digestion of food, but so far measuring these has required invasive intubation techniques. This paper describes a non-invasive magnetic resonance imaging (MRI) technique for measuring small bowel water content which has been validated using naso-duodenal infusion. Eighteen healthy volunteers were intubated, with the tube position being verified by MRI. After a baseline MRI scan, each volunteer had eight 40 ml boluses of a non-absorbable mannitol and saline solution infused into their proximal small bowel with an MRI scan being acquired after each bolus. The MRI sequence used was an adapted magnetic resonance cholangiopancreatography sequence. The image data were thresholded to allow for intra- and inter-subject signal variations. The MRI measured volumes were then compared to the known infused volumes. This MRI technique gave excellent images of the small bowel, which closely resemble those obtained using conventional radiology with barium contrast. The mean difference between the measured MRI volumes and infused volumes was 2% with a standard deviation of 10%. The maximum 95% limits of agreement between observers were -15% to +17% while measurements by the same operator on separate occasions differed by only 4%. This new technique can now be applied to study alterations in small bowel fluid absorption and secretion due to gastrointestinal disease or drug intervention.

  5. Study of the Total Electron Content in Mars ionosphere from MARSIS data set

    NASA Astrophysics Data System (ADS)

    Bergeot, Nicolas; Witasse, Olivier; Kofman, Wlodek; Grima, Cyril; Mouginot, Jeremie; Peter, Kerstin; Pätzold, Martin; Dehant, Véronique

    2016-04-01

    Centimeter level accuracy on the signal delay will be required on X-band radio link for future Mars landers such as InSIGHT, aiming at better determining the interior structure of Mars. One of the main error sources in the estimated signal delay is directly linked to the Total Electron Content (TEC) values at Earth and Mars ionosphere level. While the Earth ionosphere is now well modeled and monitored at regional and global scales, this is not the case concerning the Mars' upper atmosphere. The present paper aims at establishing the basis to model the climatological behavior of the TEC on a global scale in the Mars' ionosphere. For that we analyzed ˜8.5 years of data (mid-2005 to 2014) of the vertical Total Electron Content (vTEC) expressed in TEC units (1 TECu = 1016e-.m-2) from the Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) radar. Our study takes advantage of the double data set of EUV solar index and Mars vTEC data to develop an empirical Model of Mars Ionosphere (MoMo). The finality of this model is to predict the vTEC at a given latitude, solar zenith angle and season taking only F10.7P solar index as input. To minimize the differences during the least-square adjustment between the modeled and observed vTEC, we considered (1) a 4th-order polynomial function to describe the vTEC diurnal behavior (2) a discretization with respect to Mars seasons (depending on Ls) and (3) two latitudinal sectors (North and South hemispheres). The mean of the differences between the model and the observations is 0.00±0.07 TECu with an error of the model around 0.1 TECu depending on the Solar Zenith Angle (SZA), season and hemisphere of interest (e.g. rms 0.12 TECu for SZA equal to 50°±5° in the Northern hemisphere during the spring season). Additionally, comparison with 250 Mars Express radio occultation data shows differences with MoMo predictions of 0.02±0.06 TECu for solar zenith angles below 50 degrees. Using the model we (1) highlighted

  6. Content analysis in studies using the clinical-qualitative method: application and perspectives.

    PubMed

    Campos, Claudinei José Gomes; Turato, Egberto Ribeiro

    2009-01-01

    Content analysis comprises a set of techniques for organizing communication/information - a procedure used with qualitative data to make themes/topics and concepts/knowledge emerge. Communication content, considering human written or spoken discourse, is complex and presents valuable polysemous characteristic. With the dissemination of the clinical-qualitative method, the use of content analysis, considered an important methodological tool, raises theoretical-practical issues that need to be taken into consideration for its academically precise use. Thus, this article aimed to enumerate specific elements of the content analysis technique and discuss its suitability for the clinical-qualitative method that combines generic qualitative methods from Human and Cultural Sciences with the area of Health Sciences. Concepts were selected due to their pertinence, use and eventual adaptation to the method focused on.

  7. Is Content of Medical Journals Related to Advertisements? Case-control Study

    PubMed Central

    Vlassov, Vasiliy V.

    2007-01-01

    Aim To assess the relatedness of journal content to paid advertisements published in the journal. Methods The case-control study was performed on a convenience sample of 7 journals subscribed by Central Medical Library in Moscow – 4 international (American Journal of Hypertension, British Journal of General Practice, The Lancet, and New England Journal of Medicine) and 3 Russian peer reviewed journals (Terapevticheskii Arkhiv, Khirurgiia, and Voeno-Meditsinskii Zhurnal). In each issue containing a paid advertisement, classifieds excluded, we searched for articles related to the advertised product and compared this issue with a control issue – the next or a later issue without this advertisement. Results In American Journal of Hypertension (33 issues from 2002-2004) 94 placements of advertisements were found, 7 of which were closely related to the article topic in the same issue (7/94) vs 2/66 in the control issue. The odds ratio (OR) and 95% confidence interval (CI) for advertisements to be accompanied by related articles was OR, 2.6; 95%CI, 0.5-13). In British Journal of General Practice (27 issues from 2003-2005) there were 7/63 advertisements related to the article topic vs 0/28 in the control issue (OR, 7.2; 95% CI, 1.3 to 44). In The Lancet (49 issues from 2004) there were 8/162 advertisements related to the article topic vs 8/104 in the control issue (OR, 0.6; 95% CI, 0.3-1.5). In New England Journal of Medicine (37 issues from 2004) there were 12/81 advertisements related to the article topic vs 8/75 in the control issue (OR, 1.5; 95% CI, 0.56-3.79). In Terapevticheskii Arkhiv (10 issues from 2004) there were 38/93 advertisements related to the article topic vs 1/83 in the control issue (OR, 56.66; 95% CI, 4.4-253). In Khirurgiia (25 issues from 2003-2005) there were 3/83 advertisements related to the article topic vs 0/70 in the control issue (OR, 2.7; 95% CI, 0.3-26). In Voeno-Meditsinskii Zhurnal (33 issues from 2003-2005) there were 17

  8. Effect of intracellular P content on phosphate removal in Scenedesmus sp. Experimental study and kinetic expression.

    PubMed

    Ruiz-Martínez, A; Serralta, J; Romero, I; Seco, A; Ferrer, J

    2015-01-01

    The present work determines the effect of phosphorus content on phosphate uptake rate in a mixed culture of Chlorophyceae in which the genus Scenedesmus dominates. Phosphate uptake rate was determined in eighteen laboratory batch experiments, with samples taken from a progressively more P-starved culture in which a minimum P content of 0.11% (w/w) was achieved. The results obtained showed that the higher the internal biomass P content, the lower the phosphate removal rate. The highest specific phosphate removal rate was 6.5mgPO4-PgTSS(-1)h(-1). Microalgae with a P content around 1% (w/w) attained 10% of this highest removal rate, whereas those with a P content of 0.6% (w/w) presented 50% of the maximum removal rate. Different kinetic expressions were used to reproduce the experimental data. Best simulation results for the phosphate uptake process were obtained combining Steele equation and Hill function to represent the effect of light and intracellular phosphorus content, respectively.

  9. [Correlation study on lignin contents of Schisandra chinensis and ecological factors].

    PubMed

    Lin, Hong-Mei; Han, Hong-Xiang; Li, Yue-Hua; Yang, Li-Min

    2013-12-01

    The contents of schisandrin, schizandrin A, B and C were determined by HPLC, and the effects of the climate factors and altitude on lignin contents were analyzed in order to select the optimal cultivation area of S. chinensis. The lignin contents were analyzed by HPLC using a ZORBAX SB-C18 column (4.6 mm x 250 mm, 5 microm). The column temperature and detection wave length were set at 35 degrees C and 254 nm, respectively. Methanol-water was used as the mobile phase in gradient elution mode and the flow-rate was 1.0 mL min(-1). The method had a good repeatability, stability and accuracy. The correlation of climate factors and lignins contents was analyzed by SPSS software. The results showed that the schizandrin A content in S. chinensis fruits were higher than 0.4% in Ji'an, Liuhe, Antu and Fusong in Jilin province, which met the quality requirement. It had significant linear negative correlation relationship between schisandrin, schizandrin A, B and altitude, the contents decreased with the increase of altitude. The significant negative linear fitting coefficient was 0.844 1 between schisandrin and altitude; but it had not significant correlation between schizandrin C and altitude. A significant positive correlation of climate factors and the contents of S. chinensis lignins were mainly the temperature factors (the average annual temperature, the highest temperature in July, the average temperature in July, the highest temperature in January, the average temperature in January) and precipitation factor (average annual precipitation), which reveals that higher temperature and precipitation were helpful to the formation and accumulation of lignins of S. chinensis. So the cultivation area of S. chinensis should be in the low elevations region with warm and rainy climate.

  10. Content Peculiarities of Master's Professional Foreign Language Training in Translation Studies and Interpretation at the Universities of Slovakia

    ERIC Educational Resources Information Center

    Shumeiko, Natalia

    2016-01-01

    The article is devoted to the content analysis of peculiarities of Master's professional foreign language training in Translation Studies and Interpretation at the universities of Slovakia. In the context of globalization and integration processes the study of European countries' experience, in particular, of the Slovak Republic has been…

  11. Freedom in the Selection of Course Content: A Case-Study of a Course without a Syllabus.

    ERIC Educational Resources Information Center

    Cowan, John

    1978-01-01

    Described is a study of the feasibility and desirability of offering undergraduates freedom to select the course content in a first year course on the properties and use of civil engineering materials. A report of a series of interviews with students participating in the study is appended. (JMD)

  12. Cognitive Objectives Revealed by Classroom Questions in "Process-Oriented" and "Content-Oriented" Secondary Social Studies Programs.

    ERIC Educational Resources Information Center

    Tinsley, Drew C.; And Others

    This study investigates the cognitive nature of teacher-pupil questions in "process oriented" and "content oriented" secondary social studies programs. Subjects were five classes selected from a program viewed by both teachers and pupils as process-oriented; five from a program viewed by both teachers and pupils as content…

  13. Curriculum-Based Measurement in the Content Areas: Vocabulary Matching as an Indicator of Progress in Social Studies Learning

    ERIC Educational Resources Information Center

    Espin, Christine A.; Shin, Jongho; Busch, Todd W.

    2005-01-01

    The purpose of this study was to examine the reliability and validity of curriculum-based measures as indicator of growth in content-area learning. Participants were 58 students in 2 seventh-grade social studies classes. CBM measures were student- and administrator-read vocabulary-matching probes. Criterion measures were performance on a knowledge…

  14. Developing Pre-Service Teachers' Technological Pedagogical Content Knowledge for Teaching Mathematics with the Geometer's Sketchpad through Lesson Study

    ERIC Educational Resources Information Center

    Meng, Chew Cheng; Sam, Lim Chap

    2013-01-01

    The purpose of this study was to develop pre-service secondary teachers' technological pedagogical content knowledge (TPACK) for teaching mathematics with The Geometer's Sketchpad (GSP) through Lesson Study (LS). Specifically, a single-group pretest-posttest design was employed to examine whether there was a significant difference in the…

  15. Content Analysis of 1998-2012 Empirical Studies in Science Reading Using a Self-Regulated Learning Lens

    ERIC Educational Resources Information Center

    Hsu, Ying-Shao; Yen, Miao-Hsuan; Chang, Wen-Hua; Wang, Chia-Yu; Chen, Sufen

    2016-01-01

    There is an increasing interest in conducting reading-related studies in science education using a self-regulated learning (SRL) lens. This exploration involved a content analysis of 34 articles (38 studies in total) in highly regarded journals from 1998 to 2012 using an SRL interpretative framework to reveal critical features and relationships in…

  16. A Study of the Neutral Hydrogen Content of Blue Compact Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    MacHattie, Jeremy A.

    The results of a study of the neutral hydrogen (HI) content and distribution within a sample of 18 blue compact dwarf galaxies (BCDs) are presented. An investigation of the behaviour of the gas-to-dust ratio (GDR) as a function of metallicity (Z) is also presented. Observations of these BCDs was performed using the Very Large Array (VLA) in 2009, a year in which the array was undergoing a technological upgrade to the the Karl G. Jansky VLA (JVLA). The observations were reduced and images processed using the Astronomical Image Processing Software (AIPS), and data cubes for each galaxy were produced. The results include detections of eleven HI lines (two new detections) and ten background continuum sources (two new discoveries). All detections are at a higher resolution and/or sensitivity than previous measurements. These detections spanned a large range of line widths and H I masses; some masses comparable to those in normal galaxies. Of particular interest was the discovery of a compact absorption feature in the dwarf galaxy Haro 11. A paper submitted to the Monthly Notices of the Royal Astronomical Society (MNRAS) Letters on this discovery is presented. Another significant result was the discovery of a highly extended and massive HI region in the dwarf galaxy CGCG 297-017. For those galaxies with no detected HI line or radio continuum, an upper limit to the flux density was computed, which was used to derive upper limits to the HI mass or star-formation rate (SFR) respectively. Three HI flux density upper limits are new results, and seven continuum flux density upper limits are also new. The GDR-Z relation at low metallicities shows a potential power law or broken power law relation with a turning point at Z=7.96 or Z=8.05. To within error, these turning points and power law indices of the broken power law fits are consistent with other work.

  17. The study of optical properties and proteoglycan content of tendons by PS-OCT

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Rupani, Asha; Weightman, Alan; Wimpenny, Ian; Bagnaninchi, Pierre; Ahearne, Mark

    2011-03-01

    Tendons are load-bearing collagenous tissues consisting mainly of type I collagen and various proteoglycans (PGs) including decorin and versican. It is widely accepted that highly orientated collagen fibers in tendons a play critical role for transferring tensile stress and demonstrate birefringent optical properties. However, the influence that proteoglycans have on the optical properties of tendons is yet to be fully elucidated. Tendinopathy (defined as a syndrome of tendon pain, tenderness and swelling that affects the normal function of the tissue) is a common disease associated with sporting injuries or degeneration. PG's are the essential components of the tendon extracellular matrix; changes in their quantities and compositions have been associated with tendinopathy. In this study, polarization sensitive optical coherence tomography (PS-OCT) has been used to reveal the relationship between proteoglycan content/location and birefringent properties of tendons. Tendons dissected from freshly slaughtered chickens were imaged at regular intervals by PS-OCT and polarizing light microscope during the extraction of PGs or glycosaminoglycans using established protocols (guanidine hydrochloride (GuHCl) or proteinase K solution). The macroscopic and microscopic time lapsed images are complimentary; mutually demonstrating that there was a higher concentration of PG's in the outer sheath region than in the fascicles; and the integrity of the sheath affected extraction process and the OCT birefringence bands. Extraction of PGs using GuHCl disturbed the organization of local collagen bundles, which corresponded to a reduction in the frequency of birefringence bands and the band width by PS-OCT. The feature of OCT penetration depth helped us to define the heterogeneous distribution of PG's in tendon, which was complimented by polarizing light microscopy. The results provide new insight of tendon structure and also demonstrate a great potential for using PS-OCT as a

  18. Study of Total Electron Content distribution over Indian sector by using Coherent Radio Beacon Experiment (CRABEX)

    NASA Astrophysics Data System (ADS)

    Joshi, Shivani; Das, Rupesh M.; Upadhayaya, Arun Kumar; Singh Dabas, Raj; Ravindran, Sudha; Sharma, Rajneesh

    The trans-ionospheric communications and navigations needs to realize the dynamics of low and equatorial region ionosphere on real time basis. For this purpose the Total Electron Content (TEC) data, obtained with the help of a chain of three coherent radio beacon (CRABEX) receivers installed over the Indian sector along with a common meridian, are used. The stations are so chosen that one station i.e. Trivandrum (8.43° N, 76.98° E) is situated over geomagnetic equator, second station i.e. Bhopal (23.29° N, 77.46° E) is situated over equatorial ionization anomaly region and third station i.e. Delhi (28.6° 7 N, 77.22° E) is situated outside the anomaly zone. CRABEX receivers measure the differential Doppler phase and amplitudes of 150 and 400 MHz signals from Naval Ionospheric Measuring System (NIMS) satellites. The ionospheric TEC estimation depends on the measured phase difference and initial phase offset of two coherent signals. The phase offset is evaluated by using Lietinger two-station method. The estimated TEC is then used to study its day-to-day variation over the Indian zone and night-time TEC distribution during the Spread-F and no spread-F conditions. The result also shows the growth and decay of equatorial anomaly including the nighttime enhancement of electron density over low latitude region. The results are also compared with TEC value derived from the PIM and IRI-2001 models. The result gives a clear picture of latitudinal distribution of TEC over Indian zone with time and shows that the value derived from the PIM and IRI-2001 model are over estimating from the actual observed TEC value during the day time as well as during night time. The crest of EIA (equatorial ionization anomaly) derived from the models is also differed from actual observed one.

  19. [Comparative study on hyperspectral inversion accuracy of soil salt content and electrical conductivity].

    PubMed

    Peng, Jie; Wang, Jia-Qiang; Xiang, Hong-Ying; Teng, Hong-Fen; Liu, Wei-Yang; Chi, Chun-Ming; Niu, Jian-Long; Guo, Yan; Shi, Zhou

    2014-02-01

    The objective of the present article is to ascertain the mechanism of hyperspectral remote sensing monitoring for soil salinization, which is of great importance for improving the accuracy of hyperspectral remote sensing monitoring. Paddy soils in Wensu, Hetian and Baicheng counties of the southern Xinjiang were selected. Hyperspectral data of soils were obtained. Soil salt content (S(t)) an electrical conductivity of 1:5 soil-to-water extracts (EC(1:5)) were determined. Relationships between S(t) and EC(1:5) were studied. Correlations between hyperspectral indices and S(t), and EC(1:5) were analyzed. The inversion accuracy of S(t) using hyperspectral technique was compared with that of EC(1:5). Results showed that: significant (p<0.01) relationships were found between S(t) and EC(1:5) for soils in Wensu and Hetian counties, and correlation coefficients were 0.86 and 0.45, respectively; there was no significant relationship between S(t) and EC(1:5) for soils in Baicheng county. Therefore, the correlations between S(t) and EC(1:5) varied with studied sites. S(t) and EC(1:5) were significantly related with spectral reflectance, first derivative reflectance and continuum-removed reflectance, respectively; but correlation coefficients between S(t) and spectral indices were higher than those between EC(1:5) and spectral indices, which was obvious in some sensitive bands for soil salinization such as 660, 35, 1229, 1414, 1721, 1738, 1772, 2309 nm, and so on. Prediction equations of St and EC(1:5) were established using multivariate linear regression, principal component regression and partial least-squares regression methods, respectively. Coefficients of determination, determination coefficients of prediction, and relative analytical errors of these equations were analyzed. Coefficients of determination and relative analytical errors of equations between S(t) and spectral indices were higher than those of equations between EC(1:5) and spectral indices. Therefore, the

  20. Investigation of Polyhenolic Content of Rose Hip (Rosa canina L.) Tea Extracts: A Comparative Study

    PubMed Central

    İlbay, Zeynep; Şahin, Selin; Kırbaşlar, Ş. İsmail

    2013-01-01

    Three different brands of Rose hip (Rosa canina L.) tea were extracted with water, ethanol (EtOH), methanol (MeOH), and aqueous mixtures (50%, v/v) by ultrasound-assisted extraction (UAE) and Soxhlet methods. Total phenolic content was determined according to the Folin-Ciocalteu method. The results were presented by means of the extract yields and total phenolic contents, expressed in gallic acid equivalent (GAE) per g of dried matter (DM). The greatest amount of extract observed in tea samples was obtained by UAE through water with the value of 619.37 ± 0.58 mg/g DM. Regarding the phenolic content, the best result was achieved by the Soxhlet method through 50% MeOH mixture (59.69 ± 0.89 mg GAE/g DM), followed by the UAE method with water (48.59 ± 0.29 mg GAE/g DM). PMID:28239095

  1. A study of quantitative content analysis of health messages in U.S. media from 1985 to 2005.

    PubMed

    Manganello, Jennifer; Blake, Nancy

    2010-07-01

    Content analysis is a research method that was traditionally utilized by communication scholars, but as the study of media messages has grown, scholars in other fields have increasingly relied on the methodology. This paper reports on a systematic review of studies using quantitative content analysis methods to examine health messages in the mass media, excluding the Internet, from 1985 to 2005. We searched for health-related content analysis studies published in peer-reviewed journals, identifying 441 articles meeting inclusion criteria. We examined article attributes including theories used, topics, media type, and intercoder reliability measures, and looked at differences over time. Our findings show that studies focusing on health-related messages increased from 1985 to 2005. During this time, studies primarily examined magazines, television, and newspapers, with an emphasis on topics related to substance use, violence, sex, and obesity and body image. Results suggest that studies published in communication journals are significantly more likely to include intercoder reliability data and theory discussion. We recommend that all publications, regardless of discipline or impact factor, request the inclusion of intercoder reliability data reported for individual variables, and suggest that authors address theoretical concepts when appropriate. We also encourage authors to include the term "content analysis," as well as media type and health topic studied, as keywords to make it easier to locate articles of interest when conducting literature searches.

  2. Feasibility study of determination of high-fructose syrup content of Acacia honey by terahertz technique

    NASA Astrophysics Data System (ADS)

    Liu, Wen; Zhang, Yuying; Han, Donghai

    2016-11-01

    The authenticity problem of honey with difficult identification and great economic value highlights the certain limitations of the existing examination methods to distinguish the inauthentic honey. Terahertz technique is sensitive to water and has abundant information about saccharides' intermolecular interactions . This paper is tried to determine high-fructose-syrup content of Acacia honey by terahertz technique combined with chemometric methods. RMSEC and RMSEP of PLS model was 0.0967 and 0.108, respectively, confirming the reliability of the technique. This work shows that it was possible to determine high-fructose-syrup content of Acacia honey by terahertz technique.

  3. Study on lycopene and antioxidant contents variations in tomatoes under air-drying process.

    PubMed

    Chang, C-H; Liu, Y-C

    2007-11-01

    Effects of factors such as tomato cultivars, drying temperatures (40, 80, and 120 degrees C), and drying time (0 to 240 min) on tomato lycopene and the major antioxidant contents (MACs, herein as the sum of total phenolics and total flavonoids) during an air-drying process were investigated. The results showed that lycopene contents increased under all the drying temperatures during the first 60 min. However, the red tomato cultivars, that is, HR, SN, and TTL, exhibited a significant decrease in lycopene contents under 120 degrees C after drying for 75 min. According to the experimental data, an MAC threshold value of 500 mg/100 g dry matter of tomato is proposed. When the MAC is lower than this value during air-drying, lycopene contents in all tomato cultivars would drop rapidly. In addition, the tomatoes in yellow color group, containing more MACs initially and retaining more MACs under air-drying at 40 to 80 degrees C, are proposed to be the proper tomato cultivars for thermal processing.

  4. A Case Study of Alternatively Trained Science Teachers: Attainment of Pedagogical Content Knowledge

    ERIC Educational Resources Information Center

    Duncan, Benjamin R.

    2013-01-01

    Elements essential to effective teaching are closely aligned with the domains of a teacher's pedagogical content knowledge (PCK) (Park & Oliver, 2008). Often, alternatively trained teachers enter the teaching profession lacking exposure to pedagogical events that allow these educators opportunities to reflect on their practice and construction…

  5. The Next Generation of Psychological Autopsy Studies: Part I. Interview Content

    ERIC Educational Resources Information Center

    Conner, Kenneth R.; Beautrais, Annette L.; Brent, David A.; Conwell, Yeates; Phillips, Michael R.; Schneider, Barbara

    2011-01-01

    The psychological autopsy (PA) is a systematic method to understand the psychological and contextual circumstances preceding suicide. The method requires interviews with one or more proxy respondents (i.e., informants) of decedents. The methodological challenges that need to be addressed when determining the content of these research interviews…

  6. Study on Retrieval Technique of Content-Based Agricultural Scientech Multimedia Data

    NASA Astrophysics Data System (ADS)

    Yang, Xiaorong; Wang, Wensheng

    Traditional text information-based management and utilization methods can not satisfy application demands of implicit and unstructured agriculture multimedia data. For providing a readable-friendly agriculture science & technology information service, this paper proposes a relation database model oriented multimedia data method, which implements content-based multimedia data search by indexing every kind of multimedia data.

  7. Reasoning on the Basis of Fantasy Content: Two Studies with High-Functioning Autistic Adolescents

    ERIC Educational Resources Information Center

    Morsanyi, Kinga; Handley, Simon J.

    2012-01-01

    Reasoning about problems with empirically false content can be hard, as the inferences that people draw are heavily influenced by their background knowledge. However, presenting empirically false premises in a fantasy context helps children and adolescents to disregard their beliefs, and to reason on the basis of the premises. The aim of the…

  8. Content and Language Integrated Learning through an Online Game in Primary School: A Case Study

    ERIC Educational Resources Information Center

    Dourda, Kyriaki; Bratitsis, Tharrenos; Griva, Eleni; Papadopoulou, Penelope

    2014-01-01

    In this paper an educational design proposal is presented which combines two well established teaching approaches, that of Game-based Learning (GBL) and Content and Language Integrated Learning (CLIL). The context of the proposal was the design of an educational geography computer game, utilizing QR Codes and Google Earth for teaching English…

  9. Nutrient Content of Consumed Elementary School Lunches: A Pilot Study from Sweden

    ERIC Educational Resources Information Center

    Rosander, Ulla; Rumpunen, Kimmo; Lindmark-Mansson, Helena; Gullberg, Bo; Paulsson, Marie; Holm, Ingvar

    2013-01-01

    Purpose/Objectives: Purpose was to investigate the nutrient content of Swedish school meals consumed by students in the context of national recommendations regarding food composition and intake. Methods: Composite samples of lunch meals consumed by six students during a five-day period were collected using the double portion method and analyzed…

  10. Studying Challenges in Integrating Technology in Secondary Mathematics with Technological Pedagogical and Content Knowledge (TPACK)

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2014-01-01

    This paper describes challenges encountered by two secondary mathematics teachers when they try to integrate ICT devices in their classes. These findings are based on using the Technological Pedagogical and Content Knowledge (TPACK) context, the four dimension framework developed by Niess: 1) overarching conceptions of integrating ICT, 2)…

  11. Content Analysis of Introductory Interior Design College Textbooks: A Study Revisited

    ERIC Educational Resources Information Center

    Temple, Julie A.; Potthoff, Joy K.

    2013-01-01

    Introductory interior design texts adopted by design educators present information relevant to both historical and contemporary issues in interior design. According to one author, they provide a "survey of the field of interior design as it now exists" (Pile, 2007). A comparison of the content of contemporary texts with those of more…

  12. Podcasting in Engineering Education: A Preliminary Study of Content, Student Attitudes, and Impact

    ERIC Educational Resources Information Center

    Berger, Edward

    2007-01-01

    Edward Berger describes a pilot project implemented in an undergraduate engineering mechanics course, entitled Strength of Materials to investigate whether and how students would perceive a benefit from podcasting as a pedagogical tool. Three types of podcasting content were produced: (a) video problem solutions, (b) roundtable discussions, and…

  13. Library Subject Guides: A Content Management Case Study at the Open University, UK

    ERIC Educational Resources Information Center

    Wales, Tim

    2005-01-01

    Purpose: To share the experiences and challenges faced by the Open University Library (OUL) in developing a content management (CM) system for its subject guides. Design/methodology/approach: A summary of multi-format subject guide production at the OUL is provided to justify the decision to develop a new system for their production using a…

  14. Pedagogical Content Knowledge Development and Pre-Service Physics Teacher Education: A Case Study

    ERIC Educational Resources Information Center

    Sperandeo-Mineo, R. M.; Fazio, C.; Tarantino, G.

    2006-01-01

    This paper addresses the question of how to develop prospective teachers' pedagogical content knowledge (PCK) in science teacher education. The main focus is on the knowledge transformation process and on the cognitive strategies used to shift prospective teachers' explanations within the domain of modelling thermal physical phenomena. This study…

  15. Design of Online Professional Development in Science Content and Pedagogy: A Pilot Study in Florida

    ERIC Educational Resources Information Center

    Cavanaugh, Cathy; Dawson, Kara

    2010-01-01

    The Exploring Florida Science project goals were: (1) increasing content knowledge of secondary science teachers, specifically in topics that are important to the future of the state, and (2) providing secondary science students with digital media for use in project-based learning. A team of instructional designers, educators, scientists, web…

  16. The dielectric behaviour of snow: A study versus liquid water content

    NASA Technical Reports Server (NTRS)

    Ambach, W.; Denoth, A.

    1980-01-01

    Snow is treated as a heterogeneous dielectric material consisting of ice, air, and water. The greater difference in the high frequency relative permittivity of dry snow and water allows to determine the liquid water content by measurements of the relative permittivity of snow. A plate condenser with a volume of about 1000 cv cm was used to measure the average liquid water content in a snow volume. Calibration was carried out using a freezing calorimeter. In order to measure the liquid water content in thin snow layers, a comb-shaped condenser was developed, which is the two dimensional analogon of the plate condenser. With this moisture meter the liquid water content was measured in layers of a few millimeters in thickness, whereby the effective depth of measurement is given by the penetration depth of electric field lines which is controlled by the spacing of the strip lines. Results of field measurements with both moisture meters, the plate condenser and the comb-shaped condenser, are given.

  17. Examining the English Examination. A Study of the Linguistic Content of ESLAT.

    ERIC Educational Resources Information Center

    Mohr, Eugene V.

    An analysis is presented by the Puerto Rico office of the College Board of the English as a Second Language Achievement Test (ESLAT), which was undertaken to measure the specifications and item content of the examination against the students' performance. The report, based on 400 randomly selected structure items used in one or more versions of…

  18. An ergonomic study on the navigation structure and information units of websites with multimedia content. A case study of the Xbox 360 promotional website.

    PubMed

    Ariel, Eduardo; de Moraes, Anamaria

    2012-01-01

    This paper presents an ergonomic study on the navigation structures and information units of entertainment sites with multimedia content. This research is a case study on the XBOX 360 promotional website. It analyzes the presentation of the content on a grid that simulates the spatial displacement of the screen's elements and evaluates the interaction that the page allows for, from the users' point of view.

  19. Using Reading Strategies To Reduce the Failure Rate in the Content Area. Subject: Social Studies. Grade Level: 6-7-8.

    ERIC Educational Resources Information Center

    Dobbs, Olivett

    Content area reading instruction includes two elements: the information presented in subject matter text, and the plan that teachers use to help students understand the content. According to research and interviews with social studies teachers, there is a high failure rate in the social studies content area because children have problems…

  20. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    PubMed

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

  1. The Effects of Topic Familiarity, Author Expertise, and Content Relevance on Norwegian Students' Document Selection: A Mixed Methods Study

    ERIC Educational Resources Information Center

    McCrudden, Matthew T.; Stenseth, Tonje; Bråten, Ivar; Strømsø, Helge I.

    2016-01-01

    This mixed methods study investigated the extent to which author expertise and content relevance were salient to secondary Norwegian students (N = 153) when they selected documents that pertained to more familiar and less familiar topics. Quantitative results indicated that author expertise was more salient for the less familiar topic (nuclear…

  2. Text-Selection for Teaching Reading to ESL Tertiary Students: A Study on Genre and Content Preferences

    ERIC Educational Resources Information Center

    Nordin, Razanawati; Eng, Lin Siew

    2017-01-01

    Most learners studying English language feel that their educators use irrelevant, uninteresting, and culturally unfamiliar reading materials for teaching reading. As a result, most of them struggle to comprehend the English language texts used by the teachers. Therefore, the aim of this research is to investigate the genre and content preferences…

  3. Rational, Human, Political, and Symbolic Text in Harvard Business School Cases: A Study of Structure and Content.

    ERIC Educational Resources Information Center

    Swiercz, Paul Michael; Ross, Kathleen T.

    2003-01-01

    Using a framework of organizational arenas (rational, human, political, symbolic), narrative analysis of the content of 36 Harvard Business School case studies revealed an overwhelming emphasis on the rational to the virtual exclusion of other domains. Four perceptual hazards (metathemes) that characterize rationality bias were elaborated:…

  4. The Convergence of Content, Pedagogy, and Technology in Online Professional Development for Teachers of German: An Intrinsic Case Study

    ERIC Educational Resources Information Center

    Bustamante, Carolina; Moeller, Aleidine J.

    2013-01-01

    This qualitative case study describes a unique online professional development program utilizing Web 2.0 technologies for teachers of German using the Technological Pedagogical Content Knowledge (TPACK) model as a theoretical framework to promote technology literacy, expand German language proficiency and cultural knowledge, and integrate…

  5. A Study of K-12 Teacher Interns' Incorporation of Multicultural Content and Theory into Their Teaching Practices

    ERIC Educational Resources Information Center

    Dzoole, Edith Mechelle

    2012-01-01

    This research study examined 394 K-12 teacher interns' incorporation of multicultural content and theory into their teaching practices during a 16-week internship in schools, mostly located within a 30-mile radius of Mississippi State University. The teacher interns had completed all coursework and practicum hours required by their teacher…

  6. Effects of decreasing resolution on spectral and spatial information content in an agricultural area. [Pottawatmie study site, Iowa and Nebraska

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The effects of decreasing spatial resolution from 6 1/4 miles square to 50 miles square are described. The effects of increases in cell size is studied on; the mean and variance of spectral data; spatial trends; and vegetative index numbers. Information content changes on cadastral, vegetal, soil, water and physiographic information are summarized.

  7. Individual Differences in Navigation between Sharable Content Objects--An Evaluation Study of a Learning Module Prototype.

    ERIC Educational Resources Information Center

    Gauss, Boris; Urbas, Leon

    2003-01-01

    Reports the design and evaluation of a prototype for learning modules compliant to the SCORM (Sharable Content Object Reference Model) standard for use with hypermedia systems in Web-based instruction. Discusses a study of undergraduates that considered relations between individual differences in learner characteristics, including intrinsic…

  8. A Study of the Effectiveness of Content-Based Sensitivity Training for Japanese Nurses in Oral English Classes.

    ERIC Educational Resources Information Center

    Bay, Dale

    This study investigated the effectiveness of providing content-based English language instruction to Japanese nursing students in their second and final year of professional training. Participants were taking a full-year elective class in oral English. The control group included students from the same nursing cohort who did not attend the oral…

  9. Scientific Evidence as Content Knowledge: A Replication Study with English and Turkish Pre-Service Primary Teachers

    ERIC Educational Resources Information Center

    Roberts, Ros; Sahin-Pekmez, Esin

    2012-01-01

    Pre-service teachers around the world need to develop their content knowledge of scientific evidence to meet the requirements of recent school curriculum developments which prepare pupils to be scientifically literate. This research reports a replication study in Turkey of an intervention originally carried out with pre-service primary teachers in…

  10. A Content Analytic Study of "People's Daily" in Its Socialization Process: A Case in Cross-Cultural Communication.

    ERIC Educational Resources Information Center

    Marr, Theodore J.

    The author outlines a study comparing the modes of communication in two newspapers: "Jen Min Jih Pao" (People's Daily) and the Des Moines"Register." He applies a content-category system, based on Hayakawa's trichotomy of sentence types, to the reporting of these two newspapers on five major international events: the 1967 Arab-Israeli conflict, the…

  11. Evaluation of the Bilingual Curriculum Content (BCC) Pilot Project: A Three-Year Study. First Interim Report.

    ERIC Educational Resources Information Center

    Rothfarb, Sylvia H.; And Others

    Bilingual Curriculum Content (BCC) is an instructional component of the Transitional Bilingual Basic Skills program offered to students with limited English proficiency (LEP) in the Dade County Public Schools, Florida. In BCC instruction, students learn mathematics and combined instruction (science, social studies, and health/safety) in their…

  12. State of Colorado Consumer & Family Studies CORE Curriculums of Life Management & Relationships Crosswalk with the Colorado Academic Content Standards.

    ERIC Educational Resources Information Center

    Colorado State Community Coll. and Occupational Education System, Denver.

    This document cross-references Colorado's consumer and family studies core curriculums in life management and relationships with Colorado's academic content standards. Colorado's academic standards for students in grades 9-12 in the areas of reading and writing, geography, science, history, and mathematics are cross-referenced with student…

  13. Delivering Educational Multimedia Contents through an Augmented Reality Application: A Case Study on Its Impact on Knowledge Acquisition and Retention

    ERIC Educational Resources Information Center

    Perez-Lopez, David; Contero, Manuel

    2013-01-01

    This paper presents a study to analyze the use of augmented reality (AR) for delivering multimedia content to support the teaching and learning process of the digestive and circulatory systems at the primary school level, and its impact on knowledge retention. Our AR application combines oral explanations and 3D models and animations of anatomical…

  14. The Influence of Content Knowledge on Teaching and Learning in Traditional and Sport Education Contexts: An Exploratory Study

    ERIC Educational Resources Information Center

    Iserbyt, Peter; Ward, Phillip; Martens, Jonas

    2016-01-01

    Background: Our understanding of the role in which content knowledge (CK) can strengthen instructional models and how that knowledge matters for professional development is limited. It is contended that mere use of an instructional model is insufficient to impact psychomotor learning in meaningful ways. Purpose: This study was conducted to…

  15. Integrating Science and Technology: Using Technological Pedagogical Content Knowledge as a Framework to Study the Practices of Science Teachers

    ERIC Educational Resources Information Center

    Pringle, Rose M.; Dawson, Kara; Ritzhaupt, Albert D.

    2015-01-01

    In this study, we examined how teachers involved in a yearlong technology integration initiative planned to enact technological, pedagogical, and content practices in science lessons. These science teachers, engaged in an initiative to integrate educational technology in inquiry-based science lessons, provided a total of 525 lesson plans for this…

  16. Origins and Expertise in the Musical Improvisations of Adults and Children: A Phenomenological Study of Content and Process

    ERIC Educational Resources Information Center

    Custodero, Lori A.

    2007-01-01

    This study explores the musical content and human processes of improvisations of children and adults using the phenomenological lenses of time, space and responsivity. Paired improvisational performances of two late-career adult composers and two 7-year-old children were analysed considering a lifespan-related perspective involving the origins of…

  17. Content Analysis of Essays from a Cross-National Survey: Implications for Teaching Strategies in Holocaust Studies.

    ERIC Educational Resources Information Center

    McRoy, James J.

    The content of essays written by randomly selected samples of 1500 U.S. and 500 British secondary students on the topic "What have I learned about Adolf Hitler?" were partitioned into theme-related assertions and analyzed. An experimental group of 150 9th- and 11th-grade male students who had studied the Holocaust also contributed papers…

  18. NMR study on mechanisms of ionic polymer-metal composites deformation with water content

    NASA Astrophysics Data System (ADS)

    Zhu, Zicai; Chen, Hualing; Wang, Yongquan; Luo, Bin; Chang, Longfei; Li, Bo; Chen, Luping

    2011-10-01

    Ionic polymer-metal composites (IPMCs) exhibit a large dynamic bending deformation under exterior electric field. The states and proportions of water within the IPMCs have great effect on the IPMCs deformation properties. This letter investigates the influence of the proportion changes of different types of water on the deformation, which may disclose the working mechanisms of the IPMCs. We give a deformation trend of IPMCs with the reduction of water content firstly. Then by the method of nuclear magnetic resonance, various water types (water bonded to sulfonates, loosely bound water and free water) of IPMCs and their proportions are investigated in the drying process which corresponds to their different deformation states. It is obtained that the deformation properties of IPMCs depend strongly on their water content and the excess free water is responsible for the relaxation deformation.

  19. Design of Online Professional Development in Science Content and Pedagogy: A Pilot Study in Florida

    NASA Astrophysics Data System (ADS)

    Cavanaugh, Cathy; Dawson, Kara

    2010-10-01

    The Exploring Florida Science project goals were: (1) increasing content knowledge of secondary science teachers, specifically in topics that are important to the future of the state, and (2) providing secondary science students with digital media for use in project-based learning. A team of instructional designers, educators, scientists, web designers and teacher educators designed an online professional development environment. Needs analysis included identification of the high incidence topics on the state science achievement test and topics of socio-scientific importance in the state. Development followed tenets of design-based research, and was guided by E-Learning for Educators standards and evaluated for content, pedagogy and usability using rubrics based on established guidelines. This paper details design, development, and evaluation frameworks, and summarizes pilot testing outcomes.

  20. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study

    PubMed Central

    Trindade, Mateus C.; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T.; Bor-Seng-Shu, Edson; Machado, Alexandre A.; Teixeira, Manoel J.; Barbosa, Egberto R.

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD. PMID:27051076

  1. Genome-Wide Association Study for Muscle Fat Content and Abdominal Fat Traits in Common Carp (Cyprinus carpio)

    PubMed Central

    Zheng, Xianhu; Kuang, Youyi; Lv, Weihua; Cao, Dingchen; Sun, Zhipeng; Sun, Xiaowen

    2016-01-01

    Muscle fat content is an important phenotypic trait in fish, as it affects the nutritional, technical and sensory qualities of flesh. To identify loci and candidate genes associated with muscle fat content and abdominal fat traits, we performed a genome-wide association study (GWAS) using the common carp 250 K SNP assay in a common carp F2 resource population. A total of 18 loci surpassing the genome-wide suggestive significance level were detected for 4 traits: fat content in dorsal muscle (MFdo), fat content in abdominal muscle (MFab), abdominal fat weight (AbFW), and AbFW as a percentage of eviscerated weight (AbFP). Among them, one SNP (carp089419) affecting both AbFW and AbFP reached the genome-wide significance level. Ten of those loci were harbored in or near known genes. Furthermore, relative expressions of 5 genes related to MFdo were compared using dorsal muscle samples with high and low phenotypic values. The results showed that 4 genes were differentially expressed between the high and low phenotypic groups. These genes are, therefore, prospective candidate genes for muscle fat content: ankyrin repeat domain 10a (ankrd10a), tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (tanc2), and four jointed box 1 (fjx1) and choline kinase alpha (chka). These results offer valuable insights into the complex genetic basis of fat metabolism and deposition. PMID:28030623

  2. Genome-Wide Association Study for Muscle Fat Content and Abdominal Fat Traits in Common Carp (Cyprinus carpio).

    PubMed

    Zheng, Xianhu; Kuang, Youyi; Lv, Weihua; Cao, Dingchen; Sun, Zhipeng; Sun, Xiaowen

    2016-01-01

    Muscle fat content is an important phenotypic trait in fish, as it affects the nutritional, technical and sensory qualities of flesh. To identify loci and candidate genes associated with muscle fat content and abdominal fat traits, we performed a genome-wide association study (GWAS) using the common carp 250 K SNP assay in a common carp F2 resource population. A total of 18 loci surpassing the genome-wide suggestive significance level were detected for 4 traits: fat content in dorsal muscle (MFdo), fat content in abdominal muscle (MFab), abdominal fat weight (AbFW), and AbFW as a percentage of eviscerated weight (AbFP). Among them, one SNP (carp089419) affecting both AbFW and AbFP reached the genome-wide significance level. Ten of those loci were harbored in or near known genes. Furthermore, relative expressions of 5 genes related to MFdo were compared using dorsal muscle samples with high and low phenotypic values. The results showed that 4 genes were differentially expressed between the high and low phenotypic groups. These genes are, therefore, prospective candidate genes for muscle fat content: ankyrin repeat domain 10a (ankrd10a), tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (tanc2), and four jointed box 1 (fjx1) and choline kinase alpha (chka). These results offer valuable insights into the complex genetic basis of fat metabolism and deposition.

  3. Numerical study on the effect of charge separation at low cloud temperature and effective water content on thunderstorm electrification

    NASA Astrophysics Data System (ADS)

    Tsenova, Boryana Dimitrova; Barakova, Denitsa; Mitzeva, Rumjana

    2017-02-01

    In the present study, a numerical model is used to evaluate the effects of low effective water content and low cloud temperature on graupel charging, charge structure and lightning activity in regions of thunderstorms. Two idealized cloud cases were simulated with MesoNH using different configurations of the main known parameterizations for noninductive charging involving ice crystal/graupel rebounding collisions. Simulations in regions with very low effective cloud water content were performed with the parameterization proposed in Mitzeva et al. (2006) based on the "Relative Growth Rate" hypothesis, while for simulations in regions with low cloud temperature, charge values from Avila et al. (2011) were used. Results showed that the inclusion of the charge separation at very low effective water content influences more the simulated cloud charge structure than does the inclusion of the charge separated at low temperatures. Also, the effect of the charge separated at very low effective water content is more significant when the original parameterization for non-inductive charging is based on the effective water content rather than on the rime accretion rate.

  4. Experimental studies on the effect of moisture content and volume resistivity on electrostatic behaviour of pharmaceutical powders.

    PubMed

    Choi, Kwangseok; Taghavivand, Milad; Zhang, Lifeng

    2017-03-15

    Pharmaceutical powders are mainly organic materials and are likely to be charged due to repeated inter-particle and particle-wall contacts during industrial processes. This study experimentally investigated the effect of moisture content (ranging from approximately 1.8 to 30wt.%) on tribocharging behaviour of pharmaceutical granules, as well as their apparent volume resistivity. The tribocharging behaviour of pharmaceutical granules was investigated using a rotating device and apparent volume resistivity was measured in a conventional volume resistivity test cell. Additional measurements were performed on individual ingredients, each having the same moisture content as that of the granules, in order to investigate the effect of each single ingredient on the apparent volume resistivity of granules. In this work, the individual ingredients used for granules were: α-Lactose Monohydrate (α-LMH), Microcrystalline Cellulose (MCC), Hydroxypropyl Methylcellulose (HPMC), and Croscarmellose Sodium (CCS). The results showed that the specific charge of granules began to increase at the moisture contents below 5wt.%, which can be referred as critical moisture content of granules. The apparent volume resistivity showed the same behaviour, indicating that the specific charge could be due to an increase in apparent volume resistivity of granules at reduced moisture content. Finally, it was shown that the apparent volume resistivity measured for granules was mainly affected by that of the α-LMH, the major component of granules accounting for 40wt.%.

  5. Elemental content of anagen hairs in a normal Caucasian population studies with proton induced X-ray emission (PIXE)

    SciTech Connect

    Forslind, B.; Li, H.K.; Malmqvist, K.G.; Wiegleb, D.

    1986-01-01

    The elemental content of anagen hair fibers in a Caucasian population of healthy females and males in the age range 10-69 years was performed to constitute a baseline for further studies of pathological conditions. Proton induced X-ray emission (PIXE) analyses were performed on single hair fibers in triplicate from 103 individuals in order to determine sulfur, zinc, calcium, and chlorine content. The hair fibers were all anagen hairs collected from a site little influenced by genetic and hormonal influences 1.5 cm above the right ear of the probands. An area 5-8 mm from the follicle bottom was chosen for the analysis in all cases to minimize effect of hair-do contamination. The average sulfur content was 0.049 g/g and the average zinc content 170 micrograms/g. These results were not significantly influenced by chloroform/ethanol rinsing before analysis. The calcium and chlorine contents were 330 micrograms/g and 0.0033 g/g respectively. The latter data are expected to be more seriously influenced by external factors (e.g., contamination) than sulfur and zinc. No correlation between elemental concentration and sex was found for sulfur and zinc in the present material. PIXE analysis of single hair fibers yields valuable information on the elemental composition of hair fibers and can be rapidly and efficiently performed after simple mounting procedures.

  6. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study.

    PubMed

    Tribl, Gotthard G; Trindade, Mateus C; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T; Bor-Seng-Shu, Edson; Machado, Alexandre A; Teixeira, Manoel J; Barbosa, Egberto R

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

  7. Free water content and monitoring of healing processes of skin burns studied by microwave dielectric spectroscopy in vivo.

    PubMed

    Hayashi, Yoshihito; Miura, Nobuhiro; Shinyashiki, Naoki; Yagihara, Shin

    2005-02-21

    We have investigated the dielectric properties of human skin in vivo at frequencies up to 10 GHz using a time-domain reflectometry method with open-ended coaxial probes. Since gamma-dispersion results from the reorientation of free water molecules, the free water content of skin is quantitatively determined by dielectric measurements. The free water content of finger skin increased by about 10% after soaking in 37 degrees C water for 30 min, and it systematically decreased again through the drying process, as expected. Thus this analytical method has been applied to the study of skin burns. The free water content of burned human cheek skin due to hydrofluoric acid was significantly lower than that of normal skin, and the burned skin recovered through the healing process. In the case of a human hand skin burn due to heat, although the free water content was almost the same as that of normal skin at the beginning, it decreased during the healing process for the first 10 days, then began to increase. Although the number of test subjects was one for each experiment, it was shown that free water content is a good indicator for evaluating skin health and can be well monitored by dielectric spectroscopy.

  8. Free water content and monitoring of healing processes of skin burns studied by microwave dielectric spectroscopy in vivo

    NASA Astrophysics Data System (ADS)

    Hayashi, Yoshihito; Miura, Nobuhiro; Shinyashiki, Naoki; Yagihara, Shin

    2005-02-01

    We have investigated the dielectric properties of human skin in vivo at frequencies up to 10 GHz using a time-domain reflectometry method with open-ended coaxial probes. Since γ-dispersion results from the reorientation of free water molecules, the free water content of skin is quantitatively determined by dielectric measurements. The free water content of finger skin increased by about 10% after soaking in 37 °C water for 30 min, and it systematically decreased again through the drying process, as expected. Thus this analytical method has been applied to the study of skin burns. The free water content of burned human cheek skin due to hydrofluoric acid was significantly lower than that of normal skin, and the burned skin recovered through the healing process. In the case of a human hand skin burn due to heat, although the free water content was almost the same as that of normal skin at the beginning, it decreased during the healing process for the first 10 days, then began to increase. Although the number of test subjects was one for each experiment, it was shown that free water content is a good indicator for evaluating skin health and can be well monitored by dielectric spectroscopy.

  9. Sensitivity of global ocean heat content from reanalyses to the atmospheric reanalysis forcing: A comparative study

    NASA Astrophysics Data System (ADS)

    Storto, Andrea; Yang, Chunxue; Masina, Simona

    2016-05-01

    The global ocean heat content evolution is a key component of the Earth's energy budget and can be consistently determined by ocean reanalyses that assimilate hydrographic profiles. This work investigates the impact of the atmospheric reanalysis forcing through a multiforcing ensemble ocean reanalysis, where the ensemble members are forced by five state-of-the-art atmospheric reanalyses during the meteorological satellite era (1979-2013). Data assimilation leads the ensemble to converge toward robust estimates of ocean warming rates and significantly reduces the spread (1.48 ± 0.18 W/m2, per unit area of the World Ocean); hence, the impact of the atmospheric forcing appears only marginal for the global heat content estimates in both upper and deeper oceans. A sensitivity assessment performed through realistic perturbation of the main sources of uncertainty in ocean reanalyses highlights that bias correction and preprocessing of in situ observations represent the most crucial component of the reanalysis, whose perturbation accounts for up to 60% of the ocean heat content anomaly variability in the pre-Argo period. Although these results may depend on the single reanalysis system used, they reveal useful information for the ocean observation community and for the optimal generation of perturbations in ocean ensemble systems.

  10. LCA case study on lawn establishment and maintenance with various peat and compost contents in substrates.

    PubMed

    Silvenius, Frans; Niemeläinen, Oiva; Kurppa, Sirpa

    2016-07-01

    The environmental impacts of the establishment and maintenance of lawn, including the production and use of various substrates, were analyzed by life cycle assessment (LCA). The project focused on comparing substrates with different peat and compost contents using pilot substrates and developed a calculation tool to optimize landscaping from an ecological perspective. The impact categories were climate change, aquatic eutrophication, acidification, and use of primary energy. Life cycle assessment methodology and ISO standards 14040 and 14044 were used. Two thousand tons of substrates per hectare of lawn area were assumed to be needed; this large amount explains the importance of the substrate properties for all of the impact categories. Degradation of peat was the most significant factor of the influence of climate; thus, the most effective means of reducing the impact of landscaping on climate is to replace peat with compost. Nitrous oxide and methane emissions were related to the use of compost, but most of these emissions will occur regardless of how the sludge or biowaste is treated. Ammonia emissions from composting were the most important factor for acidification. The significance of fuel consumption by machinery in lawn establishment and mowing was low. The high contents of N and P in compost-based substrates may lead to high nutrient emissions into water systems, which can have significant local impact. The tool helps optimize substrate contents to minimize the environmental effects. Integr Environ Assess Manag 2016;12:459-464. © 2016 SETAC.

  11. Comparative study on the vitamin C contents of the food legume seeds.

    PubMed

    Moriyama, Michie; Oba, Kazuko

    2008-02-01

    We found that dehydrated legume seeds (6 genera, 19 species and cultivated varieties) contained considerable amounts of vitamin C (VC). The average value of total VC content per 100 g of dry weight in dehydrated seeds varied from 0.24 mg (kidney beans) to 4.14 mg (green peas). Yard beans showed highest values among all legumes examined here in the both dehydrated and rehydrated forms (3.19 and 10.8 mg, respectively). By soaking for 16 h in the dark at 20(o)C, total VC contents of black grams and mung beans increased to 3.1- and 4.5-fold, respectively. However, three varieties of green peas (Hakuryu, Kurumeyutaka, and Nankaimidori) significantly lost their VC during the same soaking treatment. Total VC content of a rehydrated and cooked mung beans was higher than that of a dehydrated form. Appreciable amounts of total VC were detected in the immature seeds of six different genera such as yard beans, kidney beans, broad beans, green peas, soybeans and peanuts. Except for mung beans, 70-100% of VC in dehydrated seeds of adzuki beans, broad beans, green peas, black soybeans, and soybeans was lost by boiling. Total VC and L-ascorbic acid in mung beans, green peas, broad beans, black soybeans, and adzuki beans remained even after boiling, suggesting that it is possible to obtain VC from the cooked forms of these legume seeds.

  12. Correlative study of fluoride content in urine, serum and urinary calculi.

    PubMed

    Rathee, N; Garg, P; Pundir, C S

    2004-07-01

    Fluoride content was measured in 100 urinary stones retrieved by open surgery of stone formers admitted at PGIMS Rohtak and their respective urine and serum and compared with those of healthy individuals. The concentration of fluoride was also measured in the sources of drinking water of these stone formers. The concentration of fluoride was definitely significantly higher in serum (p>0.01) and highly significantly higher in urine (p>-0.001) of stone formers compared to those of healthy individuals. The content of oxalate in serum and 24 h urine of the stone formers was also measured, which was increased significantly (p<0.005 and p<0.001) compared to healthy individuals. The concentration of fluoride was probably significantly higher in drinking water of these stone formers than the normal ones. There was a positive correlation between the content of fluoride of urinary stones and urine of stone patients (r=.88); stone and serum (r=.62); drinking water and stone (r=.85) and their urine and serum (r=.54); urine and drinking water (r=.83) and serum and water (r=.51). These results indicate a definite role of fluoride in urinary stone formation.

  13. A preliminary study of a Peruvian diet using dietary analysis and hair mineral content as indicators.

    PubMed

    Tueller, Daniel J; Eggett, Dennis L; Parker, Tory L

    2013-11-01

    Observations among former American residents living long-term in Peru suggested that hair health improved while in Peru. To determine if a Peruvian diet correlates with hair composition, dietary intake of nutrients and mineral content of hair were measured among Peruvian and matched US residents. Selected foods from Peru were also analyzed for mineral and antioxidant content and compared with equivalent foods available in the USA. Statistically significant differences between Peruvian and US residents' hair were found for sodium (decreased in Peru, p = 0.007) and vanadium (decreased in Peru, p = 0.03). Differences in hair composition between residencies may be explained by lower dietary sodium and vanadium intake among Peruvian residents or by lower concentrations of these minerals in Peruvian drinking water. Many significant mineral differences were also identified between Peruvian foods and their US equivalents. Although no statistically significant correlations between dietary intake and hair mineral content were found, results indicate that a Peruvian diet contributes differently to hair composition than a US diet. More research is needed to elucidate the link between a Peruvian diet and specific aspects of hair health.

  14. Developing a Conceptual Framework for Evaluation of E-Content of Virtual Courses: E-Learning Center of an Iranian University Case Study

    ERIC Educational Resources Information Center

    Akhavan, Peyman; Arefi, Majid Feyz

    2014-01-01

    The purpose of this study is to obtain suitable quality criteria for evaluation of electronic content for virtual courses. We attempt to find the aspects which are important in developing e-content for virtual courses and to determine the criteria we need to judge for the quality and efficiency of learning objects and e-content. So we can classify…

  15. Learning science content through socio-scientific issues-based instruction: a multi-level assessment study

    NASA Astrophysics Data System (ADS)

    Sadler, Troy D.; Romine, William L.; Sami Topçu, Mustafa

    2016-07-01

    Science educators have presented numerous conceptual and theoretical arguments in favor of teaching science through the exploration of socio-scientific issues (SSI). However, the empirical knowledge base regarding the extent to which SSI-based instruction supports student learning of science content is limited both in terms of the number of studies that have been conducted in this area and the quality of research. This research sought to answer two questions: (1) To what extent does SSI-based instruction support student learning of science content? and (2) How do assessments at variable distances from the curriculum reveal patterns of learning associated with SSI-based instruction? Sixty-nine secondary students taught by three teachers participated in the study. Three teachers implemented an SSI intervention focused on the use of biotechnology for identifying and treating sexually transmitted diseases. We found that students demonstrated statistically and practically significant gains in content knowledge as measured by both proximal and distal assessments. These findings support the claim that SSI-based teaching can foster content learning and improved performance on high-stakes tests.

  16. A city scale study on the effects of intensive groundwater heat pump systems on heavy metal contents in groundwater.

    PubMed

    García-Gil, Alejandro; Epting, Jannis; Garrido, Eduardo; Vázquez-Suñé, Enric; Lázaro, Jesús Mateo; Sánchez Navarro, José Ángel; Huggenberger, P; Calvo, Miguel Ángel Marazuela

    2016-12-01

    As a result of the increasing use of shallow geothermal resources, hydraulic, thermal and chemical impacts affecting groundwater quality can be observed with ever increasing frequency (Possemiers et al., 2014). To overcome the uncertainty associated with chemical impacts, a city scale study on the effects of intensive geothermal resource use by groundwater heat pump systems on groundwater quality, with special emphasis on heavy metal contents was performed. Statistical analysis of geochemical data obtained from several field campaigns has allowed studying the spatiotemporal relationship between temperature anomalies in the aquifer and trace element composition of groundwater. The relationship between temperature and the concentrations of trace elements resulted in weak correlations, indicating that temperature changes are not the driving factor in enhancing heavy metal contaminations. Regression models established for these correlations showed a very low reactivity or response of heavy metal contents to temperature changes. The change rates of heavy metal contents with respect to temperature changes obtained indicate a low risk of exceeding quality threshold values by means of the exploitation regimes used, neither producing nor enhancing contamination significantly. However, modification of pH, redox potential, electrical conductivity, dissolved oxygen and alkalinity correlated with the concentrations of heavy metals. In this case, the change rates of heavy metal contents are higher, with a greater risk of exceeding threshold values.

  17. FT-IR study of the effect of zinc exposure on the biochemical contents of the muscle of Labeo rohita

    NASA Astrophysics Data System (ADS)

    Palaniappan, PL. RM.; Renju, V. B.

    2009-01-01

    Heavy metal pollution is a major environmental problem in the modern world due to increasing human activities. Zinc is an essential element involved in a wide variety of cellular processes. However, it becomes toxic when elevated concentrations are introduced into the environment. The goal of the present study is to investigate the effect of zinc exposure on the biochemical contents of the muscle tissues of freshwater species Labeo rohita using Fourier transform infrared (FT-IR) spectroscopy. Since the muscle constitutes the greatest mass of the fish that is consumed, the present study has paid particular attention to muscle component. The result reveals that the zinc exposure causes significant changes in the biochemical contents of the L. rohita muscle tissues. In addition, it causes an alteration in the protein secondary structures by decreasing the α-helix and increasing the β-sheet contents of muscle tissues. Further, it has been observed that the administration of chelating agent D-penicillamine improves the protein and lipid contents in the muscle tissues compared to zinc exposed tissues. This result shows that D-penicillamine is the effective chelator of zinc in reducing the body burden of L. rohita fingerlings.

  18. The neural time course of art perception: an ERP study on the processing of style versus content in art.

    PubMed

    Augustin, M Dorothee; Defranceschi, Birgit; Fuchs, Helene K; Carbon, Claus-Christian; Hutzler, Florian

    2011-06-01

    A central prerequisite to understand the phenomenon of art in psychological terms is to investigate the nature of the underlying perceptual and cognitive processes. Building on a study by Augustin, Leder, Hutzler, and Carbon (2008) the current ERP study examined the neural time course of two central aspects of representational art, one of which is closely related to object- and scene perception, the other of which is art-specific: content and style. We adapted a paradigm that has repeatedly been employed in psycholinguistics and that allows one to examine the neural time course of two processes in terms of when sufficient information is available to allow successful classification. Twenty-two participants viewed pictures that systematically varied in style and content and conducted a combined go/nogo dual choice task. The dependent variables of interest were the Lateralised Readiness Potential (LRP) and the N200 effect. Analyses of both measures support the notion that in the processing of art style follows content, with style-related information being available at around 224 ms or between 40 and 94 ms later than content-related information. The paradigm used here offers a promising approach to further explore the time course of art perception, thus helping to unravel the perceptual and cognitive processes that underlie the phenomenon of art and the fascination it exerts.

  19. Comparison Study of Models Used to Prescribe Hydrometeor Water Content Values. Part 2. USSR Data

    DTIC Science & Technology

    1979-09-18

    Section Analysis, Internal Report of the Meteorology Laboratory,; AFCRL. 2. Feteris, P.J., Lisa, A.S., and Bussey, A.J. ( 1975 ) Environmental Definition...Pelrce, R.M., Lenhard, R.W., and Weiss. B.F. ( 1975 ) Comparison Sud of Models Used to Prescribe Hydrometeor Water Content Values, Part I: Preliminary...profiles were limited to intervals of six hours. Consequently, the AFGL-l sample is roughly half the size of the other two. The grand totals are 4343

  20. First Aid and Transportation Course Contents Based on Experience gained in the Iran-Iraq War: a Qualitative Study

    PubMed Central

    Sarhangi, Forogh; Gholami, Hamid Reza; Khaghanizade, Morteza; Najafi Mehri, Soheil

    2015-01-01

    Background: Effective first aid and transportation influences injury-induced mortality. But few qualitative studies have been conducted so far in this area. Objectives: The aim of this study was to identify the content of the first aid and patient transportation course based on experience gained from the Iran-Iraq war. Patients and Methods: This was a conventional qualitative content analysis study; a purposeful sample of 14 first aid and transportation experts who had worked during the Iran-Iraq war was recruited. We collected and analyzed the study data by using the semi-structured interview method and the conventional content analysis approach respectively. Each interview transcript was reviewed several times. Words, sentences, and paragraphs were labeled with codes. Codes were compared with each other and categorized according to their similarities. Similar sub-categories and categories were also grouped together and formed themes. Results: Study participants’ experiences of wartime first aid and transportation (FAT) education fell into two main themes including ‘the congruence of education and educational needs’ and ‘managers’ engagement in FAT education. The four main categories of these two themes were use of appropriate educational facilities, adopting effective teaching strategies, universal FAT education and specialized training skills. Conclusions: The two key requirements of the first aid and transportation courses are practicality and managerial engagement. We developed and provided specific guidance of FAT curriculum by using the study findings. This curriculum is recommended for educating FAT staffs, paramedics, emergency technicians, and military nurses. PMID:25825700

  1. Expert searcher, teacher, content manager, and patient advocate: an exploratory study of clinical librarian roles

    PubMed Central

    Tan, Maria C.; Maggio, Lauren A.

    2013-01-01

    Objective: The research explored the roles of practicing clinical librarians embedded in a patient care team. Methods: Six clinical librarians from Canada and one from the United States were interviewed to elicit detailed descriptions of their clinical roles and responsibilities and the context in which these were performed. Results: Participants were embedded in a wide range of clinical service areas, working with a diverse complement of health professionals. As clinical librarians, participants wore many hats, including expert searcher, teacher, content manager, and patient advocate. Unique aspects of how these roles played out included a sense of urgency surrounding searching activities, the broad dissemination of responses to clinical questions, and leverage of the roles of expert searcher, teacher, and content manager to advocate for patients. Conclusions: Detailed role descriptions of clinical librarians embedded in patient care teams suggest possible new practices for existing clinical librarians, provide direction for training new librarians working in patient care environments, and raise awareness of the clinical librarian specialty among current and budding health information professionals. PMID:23405048

  2. Indirect and direct determination of the casein content of milk by Kjeldahl nitrogen analysis: collaborative study.

    PubMed

    Lynch, J M; Barbano, D M; Fleming, J R

    1998-01-01

    The classic method for determination of milk casein is based on precipitation of casein at pH 4.6. Precipitated milk casein is removed by filtration and the nitrogen content of either the precipitate (direct casein method) or filtrate (noncasein nitrogen; NCN) is determined by Kjeldahl analysis. For the indirect casein method, milk total nitrogen (TN; Method 991.20) is also determined and casein is calculated as TN minus NCN. Ten laboratories tested 9 pairs of blind duplicate raw milk materials with a casein range of 2.42-3.05% by both the direct and indirect casein methods. Statistical performance expressed in protein equivalents (nitrogen x 6.38) with invalid and outlier data removed was as follows: NCN method (wt%), mean = 0.762, sr = 0.010, sR = 0.016, repeatability relative standard deviation (RSDr) = 1.287%, reproducibility relative standard deviation (RSDr) = 2.146%; indirect casein method (wt%), mean = 2.585, repeatability = 0.015, reproducibility = 0.022, RSDr = 0.560%, RSDR = 0.841; direct casein method (wt%), mean = 2.575, sr = 0.015, sR = 0.025, RSDr = 0.597%, RSDR = 0.988%. Method performance was acceptable and comparable to similar Kjeldahl methods for determining nitrogen content of milk (Methods 991.20, 991.21, 991.22, 991.23). The direct casein, indirect casein, and noncasein nitrogen methods have been adopted by AOAC INTERNATIONAL.

  3. Preliminary study on optimization of pH, oxidant and catalyst dose for high COD content: solar parabolic trough collector.

    PubMed

    Singh, Chandan; Chaudhary, Rubina; Gandhi, Kavita

    2013-01-22

    In the present study, solar photocatalytic oxidation has been investigated through laboratory experiments as an alternative to conventional secondary treatment for the organic content reduction of high COD wastewater. Experiments have been performed on synthetic high COD wastewater for solar photocatalytic oxidation using a parabolic trough reactor. Parameters affecting the oxidation of organics have been investigated.The experimental design followed the sequence of dark adsorption studies of organics, followed by photolytic studies (in absence of catalyst) and finally photocatalytic studies in presence and absence of additional oxidant (H2O2). All the experimental studies have been performed at pH values of 2, 4, 6,8,10 and the initial pH value of the wastewater (normal pH). For photocatalytic studies, TiO2 has been used as a photocatalyst. Optimization of catalyst dose, pH and H2O2 concentration has been done. Maximum reduction of organic content was observed at the normal pH value of the wastewater (pH = 6.8). The reaction rate was significantly enhanced in presence of hydrogen peroxide. The optimum pH other than the Normal was in the alkaline range. Acidic pH was not found to be favourable for organic content reduction. pH was found to be a dominant factor affecting reaction rate even in presence of H2O2 as an additional oxidant. Also, the solar detoxification process was effective in treating a waste with a COD level of more than 7500 mg/L, which is a otherwise a difficult waste to treat. It can therefore be used as a treatment step in the high organic wastewater treatment during the primary stage also as it effectively reduces the COD content by 86%.

  4. Preliminary study on optimization of pH, oxidant and catalyst dose for high COD content: solar parabolic trough collector

    PubMed Central

    2013-01-01

    In the present study, solar photocatalytic oxidation has been investigated through laboratory experiments as an alternative to conventional secondary treatment for the organic content reduction of high COD wastewater. Experiments have been performed on synthetic high COD wastewater for solar photocatalytic oxidation using a parabolic trough reactor. Parameters affecting the oxidation of organics have been investigated. The experimental design followed the sequence of dark adsorption studies of organics, followed by photolytic studies (in absence of catalyst) and finally photocatalytic studies in presence and absence of additional oxidant (H2O2). All the experimental studies have been performed at pH values of 2, 4, 6,8,10 and the initial pH value of the wastewater (normal pH). For photocatalytic studies, TiO2 has been used as a photocatalyst. Optimization of catalyst dose, pH and H2O2 concentration has been done. Maximum reduction of organic content was observed at the normal pH value of the wastewater (pH = 6.8). The reaction rate was significantly enhanced in presence of hydrogen peroxide. The optimum pH other than the Normal was in the alkaline range. Acidic pH was not found to be favourable for organic content reduction. pH was found to be a dominant factor affecting reaction rate even in presence of H2O2 as an additional oxidant. Also, the solar detoxification process was effective in treating a waste with a COD level of more than 7500 mg/L, which is a otherwise a difficult waste to treat. It can therefore be used as a treatment step in the high organic wastewater treatment during the primary stage also as it effectively reduces the COD content by 86%. PMID:23369352

  5. Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein.

    PubMed

    Llopis-Torregrosa, Vicent; Ferri-Blázquez, Alba; Adam-Artigues, Anna; Deffontaines, Emilie; van Heusden, G Paul H; Yenush, Lynne

    2016-07-15

    Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin-related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter. Also, the AMP kinase homologue, Snf1, and 14-3-3 proteins have been shown to regulate Jen1 via Rod1. Here, we further characterized the role of Rod1, Snf1, and 14-3-3 in the signal transduction route involved in the endocytic regulation of the Hxt6 high affinity glucose transporter by showing that Snf1 interacts specifically with Rod1 and Rog3 (Art7), that the interaction between the Bmh2 and several arrestin-related trafficking proteins may be modulated by carbon source, and that both the 14-3-3 protein Bmh2 and the Snf1 regulatory domain interact with the arrestin-like domain containing the N-terminal half of Rod1 (amino acids 1-395). Finally, using both co-immunoprecipitation and bimolecular fluorescence complementation, we demonstrated the interaction of Rod1 with Hxt6 and showed that the localization of the Rod1-Hxt6 complex at the plasma membrane is affected by carbon source and is reduced upon overexpression of SNF1 and BMH2.

  6. Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the β-Arrestin Pathway Using Molecular Dynamics Simulations*

    PubMed Central

    Cabana, Jérôme; Holleran, Brian; Leduc, Richard; Escher, Emanuel; Guillemette, Gaétan; Lavigne, Pierre

    2015-01-01

    Biased signaling represents the ability of G protein-coupled receptors to engage distinct pathways with various efficacies depending on the ligand used or on mutations in the receptor. The angiotensin-II type 1 (AT1) receptor, a prototypical class A G protein-coupled receptor, can activate various effectors upon stimulation with the endogenous ligand angiotensin-II (AngII), including the Gq/11 protein and β-arrestins. It is believed that the activation of those two pathways can be associated with distinct conformations of the AT1 receptor. To verify this hypothesis, microseconds of molecular dynamics simulations were computed to explore the conformational landscape sampled by the WT-AT1 receptor, the N111G-AT1 receptor (constitutively active and biased for the Gq/11 pathway), and the D74N-AT1 receptor (biased for the β-arrestin1 and -2 pathways) in their apo-forms and in complex with AngII. The molecular dynamics simulations of the AngII-WT-AT1, N111G-AT1, and AngII-N111G-AT1 receptors revealed specific structural rearrangements compared with the initial and ground state of the receptor. Simulations of the D74N-AT1 receptor revealed that the mutation stabilizes the receptor in the initial ground state. The presence of AngII further stabilized the ground state of the D74N-AT1 receptor. The biased agonist [Sar1,Ile8]AngII also showed a preference for the ground state of the WT-AT1 receptor compared with AngII. These results suggest that activation of the Gq/11 pathway is associated with a specific conformational transition stabilized by the agonist, whereas the activation of the β-arrestin pathway is linked to the stabilization of the ground state of the receptor. PMID:25934394

  7. Study on the Effects of Irrigation with Reclaimed Water on the Content and Distribution of Heavy Metals in Soil

    PubMed Central

    Lu, Shibao; Wang, Jianhua; Pei, Liang

    2016-01-01

    Reclaimed water is an important resource for irrigation, and exploration in making full use of it is an important way to alleviate water shortage. This paper analyzes the effects of irrigation with reclaimed water through field trials on the content and distribution of heavy metals in both tomatoes and the soil. By exploring the effects of reclaimed water after secondary treatment on the content and distribution characteristics of heavy metals in tomatoes and the heavy metal balance in the soil-crop system under different conditions, the study shows that there are no significant differences in the heavy metal content when the quantity of reclaimed water for irrigation varies. Reclaimed water for short-term irrigation does not cause pollution to either the soil environment or the crops. Nor will it cause the accumulation of heavy metals, and the index for the heavy metal content is far below the critical value of the national standard, which indicates that the vegetables irrigated with reclaimed water during their growth turn out to be free of pollutants. The heavy metals brought into the soil by reclaimed water are less than that taken away by the crops. The input and output quantities have only small effects on the heavy metal balance in the soil. This paper provides a reference for the evaluation and safety control of irrigation with reclaimed water. PMID:27005639

  8. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    PubMed

    Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

    2017-02-01

    It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

  9. Study on the Effects of Irrigation with Reclaimed Water on the Content and Distribution of Heavy Metals in Soil.

    PubMed

    Lu, Shibao; Wang, Jianhua; Pei, Liang

    2016-03-08

    Reclaimed water is an important resource for irrigation, and exploration in making full use of it is an important way to alleviate water shortage. This paper analyzes the effects of irrigation with reclaimed water through field trials on the content and distribution of heavy metals in both tomatoes and the soil. By exploring the effects of reclaimed water after secondary treatment on the content and distribution characteristics of heavy metals in tomatoes and the heavy metal balance in the soil-crop system under different conditions, the study shows that there are no significant differences in the heavy metal content when the quantity of reclaimed water for irrigation varies. Reclaimed water for short-term irrigation does not cause pollution to either the soil environment or the crops. Nor will it cause the accumulation of heavy metals, and the index for the heavy metal content is far below the critical value of the national standard, which indicates that the vegetables irrigated with reclaimed water during their growth turn out to be free of pollutants. The heavy metals brought into the soil by reclaimed water are less than that taken away by the crops. The input and output quantities have only small effects on the heavy metal balance in the soil. This paper provides a reference for the evaluation and safety control of irrigation with reclaimed water.

  10. Genetic Architecture of Natural Variation in Rice Chlorophyll Content Revealed by a Genome-Wide Association Study.

    PubMed

    Wang, Quanxiu; Xie, Weibo; Xing, Hongkun; Yan, Ju; Meng, Xiangzhou; Li, Xinglei; Fu, Xiangkui; Xu, Jiuyue; Lian, Xingming; Yu, Sibin; Xing, Yongzhong; Wang, Gongwei

    2015-06-01

    Chlorophyll content is one of the most important physiological traits as it is closely related to leaf photosynthesis and crop yield potential. So far, few genes have been reported to be involved in natural variation of chlorophyll content in rice (Oryza sativa) and the extent of variations explored is very limited. We conducted a genome-wide association study (GWAS) using a diverse worldwide collection of 529 O. sativa accessions. A total of 46 significant association loci were identified. Three F2 mapping populations with parents selected from the association panel were tested for validation of GWAS signals. We clearly demonstrated that Grain number, plant height, and heading date7 (Ghd7) was a major locus for natural variation of chlorophyll content at the heading stage by combining evidence from near-isogenic lines and transgenic plants. The enhanced expression of Ghd7 decreased the chlorophyll content, mainly through down-regulating the expression of genes involved in the biosynthesis of chlorophyll and chloroplast. In addition, Narrow leaf1 (NAL1) corresponded to one significant association region repeatedly detected over two years. We revealed a high degree of polymorphism in the 5' UTR and four non-synonymous SNPs in the coding region of NAL1, and observed diverse effects of the major haplotypes. The loci or candidate genes identified would help to fine-tune and optimize the antenna size of canopies in rice breeding.

  11. Recollection, familiarity, and content-sensitivity in lateral parietal cortex: a high-resolution fMRI study

    PubMed Central

    Johnson, Jeffrey D.; Suzuki, Maki; Rugg, Michael D.

    2013-01-01

    Numerous studies have identified brain regions where activity is consistently correlated with the retrieval (recollection) of qualitative episodic information. This ‘core recollection network’ can be contrasted with regions where activity differs according to the contents of retrieval. The present study used high-resolution fMRI to investigate whether these putatively-distinct retrieval processes engage common versus dissociable regions. Subjects studied words with two encoding tasks and then performed a memory test in which they distinguished between recollection and different levels of recognition confidence. The fMRI data from study and test revealed several overlapping regions where activity differed according to encoding task, suggesting that content was selectively reinstated during retrieval. The majority of recollection-related regions, though, did not exhibit reinstatement effects, providing support for a core recollection network. Importantly, lateral parietal cortex demonstrated a clear dissociation, whereby recollection effects were localized to angular gyrus and confidence effects were restricted to intraparietal sulcus. Moreover, the latter region exhibited a non-monotonic pattern, consistent with a neural signal reflecting item familiarity rather than a generic form of memory strength. Together, the findings show that episodic retrieval relies on both content-sensitive and core recollective processes, and these can be differentiated from familiarity-based recognition memory. PMID:23734122

  12. The effect of arsenic exposure on the biochemical and mineral contents of Labeo rohita bones: An FT-IR study

    NASA Astrophysics Data System (ADS)

    Palaniappan, PL. RM.; Vijayasundaram, V.

    2009-01-01

    Arsenic compounds are ubiquitous and widespread in the environment as a result of natural or anthropogenic occurrence. Fish are the major source of protein for human consumption. They are also a source of contamination, because of the amounts of heavy elements they can contain, some of which are highly toxic. Fish bones are high in calcium, which is an essential mineral for normal body function. It consists of water, organic material, and mineral matter. Chelating agents have been used clinically as antidotes for acute and chronic metal intoxications. In the present study, an attempt is made to investigate the bio-accumulation of arsenic and its effect on the biochemical and mineral contents of Labeo rohita bones using, Fourier transform infrared (FT-IR) spectroscopy. The results of the present study indicate that arsenic exposure induces significant reduction on the biochemical and mineral contents of the L. rohita bones. Further, the DMSA treatment significantly improves these levels. This shows that DMSA is an effective chelator for arsenic toxicity. Quantitative curve-fitting analyses of amide I band have proved useful in studying the nature and the extent of protein conformational changes. A decrease in α-helical and random coil structures and an increase in β-sheet structures have been observed due to arsenic exposure. In conclusion, the present study shows that the FT-IR spectroscopy coupled with second derivative and curve-fitting analysis gives useful information about the biochemical and mineral contents of the L. rohita bones.

  13. Reasoning on the basis of fantasy content: two studies with high-functioning autistic adolescents.

    PubMed

    Morsanyi, Kinga; Handley, Simon J

    2012-11-01

    Reasoning about problems with empirically false content can be hard, as the inferences that people draw are heavily influenced by their background knowledge. However, presenting empirically false premises in a fantasy context helps children and adolescents to disregard their beliefs, and to reason on the basis of the premises. The aim of the present experiments was to see if high-functioning adolescents with autism are able to utilize fantasy context to the same extent as typically developing adolescents when they reason about empirically false premises. The results indicate that problems with engaging in pretence in autism persist into adolescence, and this hinders the ability of autistic individuals to disregard their beliefs when empirical knowledge is irrelevant.

  14. A study of the viability of exploiting memory content similarity to improve resilience to memory errors

    SciTech Connect

    Levy, Scott; Ferreira, Kurt B.; Bridges, Patrick G.; Thompson, Aidan P.; Trott, Christian

    2014-12-09

    Building the next-generation of extreme-scale distributed systems will require overcoming several challenges related to system resilience. As the number of processors in these systems grow, the failure rate increases proportionally. One of the most common sources of failure in large-scale systems is memory. In this paper, we propose a novel runtime for transparently exploiting memory content similarity to improve system resilience by reducing the rate at which memory errors lead to node failure. We evaluate the viability of this approach by examining memory snapshots collected from eight high-performance computing (HPC) applications and two important HPC operating systems. Based on the characteristics of the similarity uncovered, we conclude that our proposed approach shows promise for addressing system resilience in large-scale systems.

  15. A study of the viability of exploiting memory content similarity to improve resilience to memory errors

    DOE PAGES

    Levy, Scott; Ferreira, Kurt B.; Bridges, Patrick G.; ...

    2014-12-09

    Building the next-generation of extreme-scale distributed systems will require overcoming several challenges related to system resilience. As the number of processors in these systems grow, the failure rate increases proportionally. One of the most common sources of failure in large-scale systems is memory. In this paper, we propose a novel runtime for transparently exploiting memory content similarity to improve system resilience by reducing the rate at which memory errors lead to node failure. We evaluate the viability of this approach by examining memory snapshots collected from eight high-performance computing (HPC) applications and two important HPC operating systems. Based on themore » characteristics of the similarity uncovered, we conclude that our proposed approach shows promise for addressing system resilience in large-scale systems.« less

  16. Studies on the content of heavy metals in Aries River using ICP-MS

    SciTech Connect

    Voica, Cezara Kovacs, Melinda Feher, Ioana

    2013-11-13

    Among the industrial branches, the mining industry has always been an important source of environmental pollution, both aesthetically and chemically. Through this paper results of ICP-MS characterization of Aries River Basin are reported. Mining activities from this area has resulted in contamination of environment and its surrounding biota. This is clearly evidenced in analyzed water samples, especially from Baia de Aries site where increased amount of trace elements as Cr, Zn, As, Se, Cd, Pb and U were founded. Also in this site greater amount of rare earth elements was evidenced also. Through monitoring of Aries River from other non-mining area it was observed that the quantitative content of heavy metals was below the maximum permissible levels which made us to conclude that the water table wasn't seriously affected (which possibly might be attributed to the cessation of mining activities in this area from a few years ago)

  17. A Detection Study of the Ionospheric Total Electron Contents Variations Using GPS Network

    NASA Astrophysics Data System (ADS)

    Choi, Byung-Kyu; Park, Jong-Uk; Lee, Sang-Jeong

    2007-12-01

    We established a regional ionospheric model for investigating ionospheric TEC (Total Electron Contents) variations over the Korean Peninsula during major geomagnetic storms. In order to monitor the ionospheric TEC variations, we used nine permanent GPS reference stations uniformly distributed in South Korea operated by the Korea Astronomy and Space Science Institute (KASI). The cubic spline smoothing (CSS) interpolation method was used to analyze the characteristics of the ionospheric TEC variations. It has been found that variations of TEC over the Korean Peninsula increase when a major geomagnetic storm occurred on November 20, 2003. The TEC has increased about one and a half of those averaged quite days at the specific time during a geomagnetic storm . It has been indicated that the KASI GPS-derived TEC has a correlation with the geomagnetic storm indices (eq. Kp and Dst indices).

  18. Genetic Diversity and Genome Wide Association Study of β-Glucan Content in Tetraploid Wheat Grains.

    PubMed

    Marcotuli, Ilaria; Houston, Kelly; Schwerdt, Julian G; Waugh, Robbie; Fincher, Geoffrey B; Burton, Rachel A; Blanco, Antonio; Gadaleta, Agata

    2016-01-01

    Non-starch polysaccharides (NSPs) have many health benefits, including immunomodulatory activity, lowering serum cholesterol, a faecal bulking effect, enhanced absorption of certain minerals, prebiotic effects and the amelioration of type II diabetes. The principal components of the NSP in cereal grains are (1,3;1,4)-β-glucans and arabinoxylans. Although (1,3;1,4)-β-glucan (hereafter called β-glucan) is not the most representative component of wheat cell walls, it is one of the most important types of soluble fibre in terms of its proven beneficial effects on human health. In the present work we explored the genetic variability of β-glucan content in grains from a tetraploid wheat collection that had been genotyped with a 90k-iSelect array, and combined this data to carry out an association analysis. The β-glucan content, expressed as a percentage w/w of grain dry weight, ranged from 0.18% to 0.89% across the collection. Our analysis identified seven genomic regions associated with β-glucan, located on chromosomes 1A, 2A (two), 2B, 5B and 7A (two), confirming the quantitative nature of this trait. Analysis of marker trait associations (MTAs) in syntenic regions of several grass species revealed putative candidate genes that might influence β-glucan levels in the endosperm, possibly via their participation in carbon partitioning. These include the glycosyl hydrolases endo-β-(1,4)-glucanase (cellulase), β-amylase, (1,4)-β-xylan endohydrolase, xylanase inhibitor protein I, isoamylase and the glycosyl transferase starch synthase II.

  19. Genetic Diversity and Genome Wide Association Study of β-Glucan Content in Tetraploid Wheat Grains

    PubMed Central

    Marcotuli, Ilaria; Houston, Kelly; Schwerdt, Julian G.; Waugh, Robbie; Fincher, Geoffrey B.; Burton, Rachel A.; Blanco, Antonio; Gadaleta, Agata

    2016-01-01

    Non-starch polysaccharides (NSPs) have many health benefits, including immunomodulatory activity, lowering serum cholesterol, a faecal bulking effect, enhanced absorption of certain minerals, prebiotic effects and the amelioration of type II diabetes. The principal components of the NSP in cereal grains are (1,3;1,4)-β-glucans and arabinoxylans. Although (1,3;1,4)-β-glucan (hereafter called β-glucan) is not the most representative component of wheat cell walls, it is one of the most important types of soluble fibre in terms of its proven beneficial effects on human health. In the present work we explored the genetic variability of β-glucan content in grains from a tetraploid wheat collection that had been genotyped with a 90k-iSelect array, and combined this data to carry out an association analysis. The β-glucan content, expressed as a percentage w/w of grain dry weight, ranged from 0.18% to 0.89% across the collection. Our analysis identified seven genomic regions associated with β-glucan, located on chromosomes 1A, 2A (two), 2B, 5B and 7A (two), confirming the quantitative nature of this trait. Analysis of marker trait associations (MTAs) in syntenic regions of several grass species revealed putative candidate genes that might influence β-glucan levels in the endosperm, possibly via their participation in carbon partitioning. These include the glycosyl hydrolases endo-β-(1,4)-glucanase (cellulase), β-amylase, (1,4)-β-xylan endohydrolase, xylanase inhibitor protein I, isoamylase and the glycosyl transferase starch synthase II. PMID:27045166

  20. Phytochemical Content and Pharma-Nutrition Study on Eleutherococcus senticosus Fruits Intractum.

    PubMed

    Załuski, Daniel; Olech, Marta; Galanty, Agnieszka; Verpoorte, Robert; Kuźniewski, Rafał; Nowak, Renata; Bogucka-Kocka, Anna

    2016-01-01

    In the past two decades public interest in herbal products has increased significantly in Europe, especially in the plant-based products from non-European traditions. Eleutherococcus senticosus has been used for the treatment of inflammatory diseases, anemia, and rheumatoid arthritis. The Eleutherococcus senticosus fruits intractum was examined for the content of phenolic acids (LC-ESI-MS/MS), minerals (AAS), TPC, and TFC (spectrophotometric assay). The antioxidant activity was determined using free radical scavenging assay and TLC-DB-DPPH(∗) dot-blot test. An anti-Hyal activity was evaluated by the spectrophotometric assay method. Cytotoxicity towards HL-60, HL-60/MX1, HL-60/MX2, CEM/C1, and CCRF/CEM leukemic cell lines was done using trypan blue test. Among eight phenolic acids, trans-caffeic acid was found in the largest amount (41.2 mg/g DE). The intractum presented a high amount of macroelements (Ca, Mg, K; 1750, 1300, and 21000 mg/kg) and microelements (Fe, Mn; 32.7, 54.3 mg/kg), respectively. The content of TPC and TFC was 130 and 92 mg/g DE, respectively. The intractum showed anti-Hyal activity (2.16-60%) and an antioxidant capacity (EC50; 52 μg/mL). The intractum most strongly inhibited the growth of HL-60, HL-60/MX1, and CCRF/CEM. A better understanding of the intractum health benefits is important in order to increase its utility and enrich dietary sources of health promoting compounds.

  1. Phytochemical Content and Pharma-Nutrition Study on Eleutherococcus senticosus Fruits Intractum

    PubMed Central

    Olech, Marta; Galanty, Agnieszka; Verpoorte, Robert; Nowak, Renata; Bogucka-Kocka, Anna

    2016-01-01

    In the past two decades public interest in herbal products has increased significantly in Europe, especially in the plant-based products from non-European traditions. Eleutherococcus senticosus has been used for the treatment of inflammatory diseases, anemia, and rheumatoid arthritis. The Eleutherococcus senticosus fruits intractum was examined for the content of phenolic acids (LC-ESI-MS/MS), minerals (AAS), TPC, and TFC (spectrophotometric assay). The antioxidant activity was determined using free radical scavenging assay and TLC-DB-DPPH∗ dot-blot test. An anti-Hyal activity was evaluated by the spectrophotometric assay method. Cytotoxicity towards HL-60, HL-60/MX1, HL-60/MX2, CEM/C1, and CCRF/CEM leukemic cell lines was done using trypan blue test. Among eight phenolic acids, trans-caffeic acid was found in the largest amount (41.2 mg/g DE). The intractum presented a high amount of macroelements (Ca, Mg, K; 1750, 1300, and 21000 mg/kg) and microelements (Fe, Mn; 32.7, 54.3 mg/kg), respectively. The content of TPC and TFC was 130 and 92 mg/g DE, respectively. The intractum showed anti-Hyal activity (2.16–60%) and an antioxidant capacity (EC50; 52 μg/mL). The intractum most strongly inhibited the growth of HL-60, HL-60/MX1, and CCRF/CEM. A better understanding of the intractum health benefits is important in order to increase its utility and enrich dietary sources of health promoting compounds. PMID:27843534

  2. A Multimedia Mobile Phone–Based Youth Smoking Cessation Intervention: Findings From Content Development and Piloting Studies

    PubMed Central

    Maddison, Ralph; McRobbie, Hayden; Bullen, Chris; Denny, Simon; Dorey, Enid; Ellis-Pegler, Mary; van Rooyen, Jaco; Rodgers, Anthony

    2008-01-01

    Background While most young people who smoke want to quit, few access cessation support services. Mobile phone–based cessation programs are ideal for young people: mobile phones are the most common means of peer communication, and messages can be delivered in an anonymous manner, anywhere, anytime. Following the success of our text messaging smoking cessation program, we developed an innovative multimedia mobile phone smoking cessation intervention. Objective The aim of the study was to develop and pilot test a youth-oriented multimedia smoking cessation intervention delivered solely by mobile phone. Methods Development included creating content and building the technology platform. Content development was overseen by an expert group who advised on youth development principles, observational learning (from social cognitive theory), effective smoking cessation interventions, and social marketing. Young people participated in three content development phases (consultation via focus groups and an online survey, content pre-testing, and selection of role models). Video and text messages were then developed, incorporating the findings from this research. Information technology systems were established to support the delivery of the multimedia messages by mobile phone. A pilot study using an abbreviated 4-week program of video and text content tested the reliability of the systems and the acceptability of the intervention. Results Approximately 180 young people participated in the consultation phase. There was a high priority placed on music for relaxation (75%) and an interest in interacting with others in the program (40% would read messages, 36% would read a blog). Findings from the pre-testing phase (n = 41) included the importance of selecting “real” and “honest” role models with believable stories, and an interest in animations (37%). Of the 15 participants who took part in the pilot study, 13 (87%) were available for follow-up interviews at 4 weeks: 12

  3. Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression

    PubMed Central

    Rosanò, Laura; Caprara, Valentina; Sestito, Rosanna; Di Castro, Valeriana; Bagnato, Anna

    2016-01-01

    Hypoxia-inducible factor-1α (HIF-1α) mediates the response to hypoxia or other stimuli, such as growth factors, including endothelin-1 (ET-1), to promote malignant progression in numerous tumors. The importance of cofactors that regulate HIF-1α signalling within tumor is not well understood. Here we elucidate that ET-1/ETA receptor (ETAR)-induced pathway physically and functionally couples the scaffold protein β-arrestin1 (β-arr1) to HIF-1α signalling. In epithelial ovarian cancer (EOC) cells, ET-1/ETAR axis induced vascular-endothelial growth factor (VEGF) expression through HIF-1α nuclear accumulation. In these cells, activation of ETAR by ET-1, by mimicking hypoxia, promoted the nuclear interaction between β-arr1 and HIF-1α and the recruitment of p300 acetyltransferase to hypoxia response elements on the target gene promoters, resulting in enhanced histone acetylation, and HIF-1α target gene transcription. Indeed, β-arr1-HIF-1α interaction regulated the enhanced expression and release of downstream targets, such as ET-1 and VEGF, required for tumor cell invasion and pro-angiogenic effects in endothelial cells. These effects were abrogated by β-arr1 or HIF-1α silencing or by pharmacological treatment with the dual ET-1 receptor antagonist macitentan. Interestingly, ETAR/β-arr1 promoted the self-amplifying HIF-1α-mediated transcription of ET-1 that sustained a regulatory circuit involved in invasive and angiogenic behaviors. In a murine orthotopic model of metastatic human EOC, treatment with macitentan, or silencing of β-arr1, inhibits intravasation and metastasis formation. Collectively, these findings reveal the interplay of β-arr1 with HIF-1α in the complexity of ET-1/ETAR signalling, mediating epigenetic modifications directly involved in the metastatic process, and suggest that targeting ET-1-dependent β-arr1/HIF-1α pathway by using macitentan may impair EOC progression. PMID:26909598

  4. (−)-Stepholidine is a potent pan-dopamine receptor antagonist of both G protein- and β-arrestin-mediated signaling

    PubMed Central

    Meade, Julie A.; Free, R. Benjamin; Miller, Nicole R.; Chun, Lani S.; Doyle, Trevor B.; Moritz, Amy E.; Conroy, Jennie L.; Watts, Val J.

    2017-01-01

    Rationale (−)-Stepholidine is a tetrahydroberberine alkaloid that is known to interact with dopamine receptors and has also been proposed as a novel antipsychotic agent. Its suggested novelty lies in the fact that it has been proposed to have D1-like receptor agonist and D2-like receptor antagonist properties. Thus, it might be effective in treating both positive and negative (cognition) symptoms of schizophrenia. However, its activity on specific dopamine receptor subtypes has not been clarified, especially with respect to its ability to activate D1-like receptors. Objectives We wished to examine the affinity and functional activity of (−)-stepholidine at each of the human dopamine receptor subtypes expressed in a defined cellular environment. Methods D1–D5 dopamine receptors were stably expressed in cell lines and their interactions with (−)-stepholidine were examined using radioligand binding and various functional signaling assays. Radioligand binding assays were also performed using bovine striatal membranes. Results (−)-Stepholidine exhibited high (nM) affinity for D1 and D5 receptors, somewhat lower (two- to four-fold) affinity for D2 and D3 receptors, and low micromolar affinity for D4 receptors. Functionally, (−)-stepholidine was ineffective in activating G protein-mediated signaling of D1-like and D2 receptors and was also ineffective in stimulating β-arrestin recruitment to any dopamine receptor subtype. It did, however, antagonize all of these responses. It also antagonized D1–D2 heteromer-mediated Ca2+ mobilization. Radioligand binding assays of D1-like receptors in brain membranes also indicated that (−)-stepholidine binds to the D1 receptor with antagonist-like properties. Conclusions (−)-Stepholidine is a pan-dopamine receptor antagonist and its in vivo effects are largely mediated through dopamine receptor blockade with potential cross-talk to other receptors or signaling proteins. PMID:25231919

  5. Participants' Accounts on Their Decision to Join a Cohort Study With an Attached Biobank: A Qualitative Content Analysis Study Within Two German Studies.

    PubMed

    Nobile, Hélène; Bergmann, Manuela M; Moldenhauer, Jennifer; Borry, Pascal

    2016-07-01

    Reliable participation and sustained retention rates are crucial in longitudinal studies involving human subjects and biomaterials. Understanding the decision to enroll is an essential step to develop adequate strategies promoting long-term participation. Semi-structured interviews were implemented with newly recruited and long-term participants randomly drawn from two ongoing longitudinal studies with a biobank component in Germany. Iterative qualitative content analysis was applied to the transcribed interviews. Participants (n = 31) expressed their decision to enroll or remain in the study as the result of the complex interplay of individual factors, institutional cues, study-related features, and societal dynamics. Different forms of trust were identified as central within the elements used to explain participation and could be compared to Dibben, Morris, and Lean's dynamic model of interpersonal trust. Given these high levels of trust, an investigation of the morality of the trustful relationship at stake between participants and research(ers) is warranted.

  6. A case study of natural variability of water vapor content in the Baltic Sea region

    NASA Astrophysics Data System (ADS)

    Jakobson, E.; Keernik, H.

    2012-12-01

    Water vapor is the most essential component of the Earth's atmosphere. It is contributing about 60 % of the natural greenhouse effect, being the resource for precipitation in the lower troposphere and playing a critical role in many chemical reactions. Therefore, its quantity must be known precisely to understand, associate and forecast meteorological processes. On the other hand, temporal as well as spatial variability of water vapor occur such a fine scales, that resolving it adequately presuppose observing systems with high sampling resolution in space and time. Regular radiosondes with 12 h or 24 h sampling interval are not sufficient for detecting fast changes neither in the humidity profiles nor in the water vapor total content. During three days (10th-12th August 2010) total of 24 radiosoundings with interval 3 h were made in Toravere, Estonia (58°15' N, 26°27' E), using GRAW DFM-06 radiosondes. Column-integrated water vapor content, known as precipitable water, varied during the campaign from 24 mm to 36 mm. The temporal variation of specific humidity was surprisingly uniform, up to 2 g/kg within any layer in the profile below 6 km. It is noteworthy, as the average values varied even one magnitude - from 12 g/kg at the ground level to 1 g/kg at 6000 m. These changes in the humidity content in the whole profile can be explained only with exchanges of the air masses. In addition to the radiosondes data, NCEP-CFSR vertical profile data of specific humidity and temperature for the Baltic Sea region (here defined as region 52° - 68° N, 12° - 32° E) was used with temporal and spatial resolution of 6 h and 0.5 degrees, respectively. For the overlapping period, NCEP-CFSR followed the measured profiles reasonably well, giving us some justice to use this model for the whole period and region. The region average of precipitable water was 22.8 mm, though local extreme values varied through the summer even one magnitude - from 4.5 mm to 51 mm. The average

  7. Women Studies in Engineering Education: Content Analysis in Three Referred Journals

    ERIC Educational Resources Information Center

    Chou, Pao-Nan

    2013-01-01

    Little is known about the research characteristics of past women studies in engineering education. In order to add knowledge base about the advanced development of women studies in current engineering education research, the purpose of the study is to investigate research characteristics of past women studies published in three referred…

  8. Study of Ionosphere Total Electron Content for the Broadband Geodetic VLBI Fringe Model

    NASA Astrophysics Data System (ADS)

    Mulero Hernandez, C. A.; Beaudoin, C. J.; Coster, A. J.; Erickson, P. J.; Niell, A. E.

    2013-12-01

    The radio telescopes used for Geodetic Very Long Baseline Interferometry (VLBI) receive signals from distant astronomical objects to provide a measure of the Earth's shape and variable rotation. However, the propagation of these signals through the Earth's ionosphere and any other plasma between the radio source and the telescope introduces a systematic error in the geodetic observable. This dispersive delay has become more critical in light of the accuracy goals set forth in the VLBI2010 specifications for the VLBI Geodetic Observing System (VGOS) which are 1mm for position and 0.1 mm/yr for stability. In order to achieve such geodetic accuracy, this error must be accurately removed. In this work we present an investigation of the accuracy of the dispersive component of delay as determined by the broadband geodetic VLBI technique. We will describe the features and implementation of a frequency-dependent forward model of this dispersive delay for VLBI. The application of this model yields an estimate of the combined ionospheric and extraterrestrial differential total electron content (TEC) using a nonlinear parametric search. We assess the quality of this VLBI-based differential TEC estimate by comparing it with differential TEC values obtained using GPS receivers near VLBI antennas.

  9. [Study on the content and carbon isotopic composition of water dissolved inorganic carbon from rivers around Xi'an City].

    PubMed

    Guo, Wei; Li, Xiang-Zhong; Liu, Wei-Guo

    2013-04-01

    In this study, the content and isotopic compositions of water dissolved inorganic carbon (DIC) from four typical rivers (Chanhe, Bahe, Laohe and Heihe) around Xi'an City were studied to trace the possible sources of DIC. The results of this study showed that the content of DIC in the four rivers varied from 0.34 to 5.66 mmol x L(-1) with an average value of 1.23 mmol x L(-1). In general, the content of DIC increased from the headstream to the river mouth. The delta13C(DIC) of four rivers ranged from -13.3 per thousand to -7.2 per thousand, with an average value of -10.1 per thousand. The delta13C(DIC) values of river water were all negative (average value of -12.6 per thousand) at the headstream of four rivers, but the delta13C(DIC) values of downstream water were more positive (with an average value of -9.4 per thousand). In addition, delta13C(DIC) of river water showed relatively negative values (the average value of delta13C(DIC) was -10.5 per thousand) near the estuary of the rivers. The variation of the DIC content and its carbon isotope suggested that the DIC sources of the rivers varied from the headstream to the river mouth. The negative delta13C(DIC) value indicated that the DIC may originate from the soil CO2 at the headstream of the rivers. On the other hand, the delta13C(DIC) values of river water at the middle and lower reaches of rivers were more positive, and it showed that soil CO2 produced by respiration of the C4 plants (like corn) and soil carbonates with positive delta13C values may be imported into river water. Meanwhile, the input of pollutants with low delta13C(DIC) values may result in a decrease of delta13C(DIC) values in the rivers. The study indicated that the DIC content and carbon isotope may be used to trace the sources of DIC in rivers around Xi'an City. Our study may provide some basic information for tracing the sources of DIC of rivers in the small watershed area in the Loess Plateau of China.

  10. A pilot study of phytoestrogen content of soy foods and traditional Chinese medicines for women's health in Hong Kong.

    PubMed

    Li, Martin; Poon, Peter; Woo, Jean

    2004-05-01

    In view of the possible health benefits of phytoestrogens, a pilot study was carried out to quantitate the phytoestrogen content of soy foods and tea commonly consumed in Hong Kong, and also of traditional Chinese medicinal (TCM) products that are prescribed for menopausal symptoms and diseases relating to the menopause. Assays of daidzein and genistein were carried out using high-performance liquid chromatography, after extraction procedures. The TCM products were found to contain phytoestrogen in quantities comparable with soy products. Moreover, certain types of Chinese tea contained large quantities of phytoestrogens in the leaves, but also yielded comparable quantities in the infusion for drinking. The phytoestrogen content of these TCM may provide a scientific basis for their actions. However, clinical efficacy can only be determined by clinical trials.

  11. Teacher- or Learner-Centred? Science Teacher Beliefs Related to Topic Specific Pedagogical Content Knowledge: A South African Case Study

    NASA Astrophysics Data System (ADS)

    Mavhunga, Elizabeth; Rollnick, Marissa

    2016-12-01

    In science education, learner-centred classroom practices are widely accepted as desirable and are associated with responsive and reformed kinds of teacher beliefs. They are further associated with high-quality Pedagogical Content Knowledge (PCK). Topic-Specific Pedagogical Content Knowledge (TSPCK), a version of PCK defined at topic level, is known to enable the transformation of topic content into a form accessible to learners. However, little is known about teacher science beliefs in relation to TSPCK and therefore the nature of likely associated classroom practices. In this study, we investigated the relationship between TSPCK and underlying science teacher beliefs following an intervention targeting the improvement of TSPCK in the topic chemical equilibrium. Sixteen final year pre-service chemistry teachers were exposed to an intervention that explicitly focussed on knowledge for transforming the content of chemical equilibrium using the five knowledge components of TSPCK. A specially designed TSPCK instrument in chemical equilibrium and the Teacher Belief Instrument (TBI) were used to capture written responses in pre- and post-tests. Additional qualitative data was collected from audio-recorded discussions and written responses from an open-ended question asked before and after the intervention. Two key findings emerged from the study. Firstly, the development of TSPCK was linked to shifts in underlying science teacher beliefs in the direction of learner-centred teaching for the majority of pre-service teachers. Secondly, this shift was not evident for all, as for some there was development of TSPCK without a shift from teacher-centred beliefs about science teaching.

  12. The Current Debate in the Social Studies Discipline Regarding an Emphasis on Content and Process.

    ERIC Educational Resources Information Center

    Calmel, Louis

    The current debate about social studies education is the focus of this paper, and the questions and the charges raised by recent surveys and reports are addressed. Survey results from the Ravitch and Finn, the Chandler, and the National Catholic Educational Association studies reflecting student ignorance of social studies knowledge are discussed.…

  13. Content-Related Interactions and Methods of Reasoning within Self-Initiated Organic Chemistry Study Groups

    ERIC Educational Resources Information Center

    Christian, Karen Jeanne

    2011-01-01

    Students often use study groups to prepare for class or exams; yet to date, we know very little about how these groups actually function. This study looked at the ways in which undergraduate organic chemistry students prepared for exams through self-initiated study groups. We sought to characterize the methods of social regulation, levels of…

  14. Using MultiMedia Content to Present Business Ethics: An Empirical Study

    ERIC Educational Resources Information Center

    Stanwick, Peter A.

    2010-01-01

    The purpose of this study is to empirically examine whether presenting a multimedia case study enhances the learning experience of students in an undergraduate management class. A questionnaire was administered before and after the presentation of the case study and the results showed that the multimedia case did indeed enhance the learning…

  15. A study of the relationship between mineral content and mechanical properties of turkey gastrocnemius tendon

    NASA Technical Reports Server (NTRS)

    Landis, W. J.; Librizzi, J. J.; Dunn, M. G.; Silver, F. H.

    1995-01-01

    The vertebrate skeletal system undergoes adaptation in response to external forces, but the relation between the skeletal changes and such forces is not understood. In this context, the variation in the amount and location of calcification has been compared with changes in mechanical properties of the normally mineralizing turkey gastrocnemius tendon using ash weight measurements, X-ray radiography, and mechanical testing. Radiographic evidence from 12- to 17-week-old birds showed calcification in only portions of gastrocnemius tendons proximal to the tarsometatarsal joint. Mechanical testing of these dissected proximal regions demonstrated an increased ultimate stress and modulus and a decreased maximum strain that appeared to parallel calcification. Further, stress-strain curves of portions of uncalcified turkey gastrocnemius tendon were shaped similar to those of other typical unmineralized tendon curves while highly calcified tendons yielded curves resembling those of bone. The proximal portions of the gastrocnemius where mineralization begins were observed to have a decreased tendon cross-sectional area compared with distal portions which do not mineralize. Based on the resultant measures of mineral content and location and mechanical properties, it is hypothesized that increased calcification is a result of increased stresses at certain locations of the tendon, perhaps the consequence of the natural forces exerted by the large leg muscles of the bird into which the gastrocnemius inserts. More specifically, tendon calcification may be the result of stress-induced exposure of charged sites on the surfaces of collagen molecules, fibrils, or fibers so that deposition of mineral and subsequent mechanical reinforcement occur in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS).

  16. Study of recombinant micro-organism populations characterized by their plasmid content per cell using a segregated model.

    PubMed

    Shene, C; Andrews, B A; Asenjo, J A

    2003-07-01

    Numerous observations from recombinant systems have shown that properties such as the specific cell growth rate and the plasmid-free cell formation rate are related, not only to the average plasmid content per cell, but also to the plasmid distribution within a population. The plasmid distribution in recombinant cultures can have an effect on the culture productivity that cannot be modelled using average values of the overall culture. The prediction of the behaviour of a plasmid content distribution and its causes and effects can only be studied using segregated models. A segregated model that describes populations of recombinant cells characterized by their plasmid content distribution has been developed. This model includes critical causes of recombinant culture instability such as the plasmid partition mechanism at cell division, plasmid replication kinetics and the effect of the plasmid content on the specific growth rate. The segregated model allows investigation of the effect of each of these causes and that of the plasmid content distribution on the observable behaviour of a recombinant culture. The effect of two partitioning mechanisms (Gaussian distribution and binomial distribution) on culture stability was investigated. The Gaussian distribution is slightly more stable. A small plasmid replication rate constant results in a very unstable culture even after short periods of time. This instability is dramatically improved for a larger value of this constant, hence improving protein synthesis. For a very narrow initial plasmid distribution, a given plasmid replication rate and partitioning mechanism can become broad even after a relatively short period of time. In contrast, a very "broad" initial distribution gave rise to a "Gamma-like" distribution profile. If we compare the results obtained in the simulations of the segregated model with those of the non-segregated one (average model), the latter model predicts much more stable behaviour, thus these

  17. Sources of variability and comparability between salmonid stomach contents and isotopic analyses: study design lessons and recommendations

    USGS Publications Warehouse

    Vinson, M.R.; Budy, P.

    2011-01-01

    We compared sources of variability and cost in paired stomach content and stable isotope samples from three salmonid species collected in September 2001–2005 and describe the relative information provided by each method in terms of measuring diet overlap and food web study design. Based on diet analyses, diet overlap among brown trout, rainbow trout, and mountain whitefish was high, and we observed little variation in diets among years. In contrast, for sample sizes n ≥ 25, 95% confidence interval (CI) around mean δ15Ν and δ13C for the three target species did not overlap, and species, year, and fish size effects were significantly different, implying that these species likely consumed similar prey but in different proportions. Stable isotope processing costs were US$12 per sample, while stomach content analysis costs averaged US$25.49 ± $2.91 (95% CI) and ranged from US$1.50 for an empty stomach to US$291.50 for a sample with 2330 items. Precision in both δ15Ν and δ13C and mean diet overlap values based on stomach contents increased considerably up to a sample size of n = 10 and plateaued around n = 25, with little further increase in precision.

  18. A COMPARATIVE STUDY OF RADIUM CONTENT AND RADON EXHALATION RATE FROM SOIL SAMPLES USING ACTIVE AND PASSIVE TECHNIQUES.

    PubMed

    Yadav, Manjulata; Prasad, Mukesh; Joshi, Veena; Gusain, G S; Ramola, R C

    2016-10-01

    Soil is the most important factor affecting the radon level in the human living environments. It depends not only on uranium and thorium contents but also on the physical and chemical properties of the soil. In this paper, the measurements of radium content and mass exhalation rate of radon from the soil samples collected from Uttarkashi area of Garhwal Himalaya are presented. The correlation between radium content and radon mass exhalation rate from soil has also been obtained. The radium was measured by gamma ray spectrometry, while the mass exhalation rate of radon has been determined by both active and passive methods. The radium activity in the soil of study area was found to vary from 45±7 to 285±29 Bq kg(-1) with an average of 99 Bq kg(-1) The radon mass exhalation rate was found to vary from 0.59 × 10(-5) to 2.2 × 10(-5) Bq kg(-1) h(-1) with an average of 1.4 × 10(-5) Bq kg(-1) h(-1) by passive technique and from 0.8 × 10(-5) to 3.2 × 10(-5) Bq kg(-1) h(-1) with an average of 1.5 × 10(-5) Bq kg(-1) h(-1) by active technique. The results suggest that the measured radium value is positively correlated with the radon mass exhalation rate measured with both the active and passive techniques.

  19. Sucrose lyophiles: a semi-quantitative study of residual water content by total X-ray diffraction analysis.

    PubMed

    Bates, S; Jonaitis, D; Nail, S

    2013-10-01

    Total X-ray Powder Diffraction Analysis (TXRPD) using transmission geometry was able to observe significant variance in measured powder patterns for sucrose lyophilizates with differing residual water contents. Integrated diffraction intensity corresponding to the observed variances was found to be linearly correlated to residual water content as measured by an independent technique. The observed variance was concentrated in two distinct regions of the lyophilizate powder pattern, corresponding to the characteristic sucrose matrix double halo and the high angle diffuse region normally associated with free-water. Full pattern fitting of the lyophilizate powder patterns suggested that the high angle variance was better described by the characteristic diffraction profile of a concentrated sucrose/water system rather than by the free-water diffraction profile. This suggests that the residual water in the sucrose lyophilizates is intimately mixed at the molecular level with sucrose molecules forming a liquid/solid solution. The bound nature of the residual water and its impact on the sucrose matrix gives an enhanced diffraction response between 3.0 and 3.5 beyond that expected for free-water. The enhanced diffraction response allows semi-quantitative analysis of residual water contents within the studied sucrose lyophilizates to levels below 1% by weight.

  20. In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

    PubMed

    Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

    2009-01-01

    During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

  1. Influence of Motivational Design on Completion Rates in Online Self-Study Pharmacy-Content Courses

    ERIC Educational Resources Information Center

    Pittenger, Amy; Doering, Aaron

    2010-01-01

    Student retention rates are a constant concern in higher education, but this concern has become especially challenging as online courses become more common and there are widespread reports of low completion rates for online, self-study courses. We evaluated four self-study online pharmacy courses with a history of very high completion rates for…

  2. Recognizing the Balance between Process and Content in Elementary Social Studies.

    ERIC Educational Resources Information Center

    Austin, Susan

    1979-01-01

    Contends that the methods used to teach social studies become secondary to the emerging trend in elementary schools of putting social studies aside in favor of the basics. Also suggests that problem-solving and decision-making skills are basic to survival in our society. (Author/KC)

  3. Design vs. Content: A Study of Adolescent Girls' Website Design Preferences

    ERIC Educational Resources Information Center

    Agosto, Denise E.

    2004-01-01

    This study considered the utility of gender schema theory in examining girls' website design preferences. It built on a previous study which identified eight website evaluation criteria related to biological sex: collaboration, social connectivity, flexibility, motility, contextuality, personal identification, inclusion, and graphic/multimedia…

  4. Electrical resistivity sounding to study water content distribution in heterogeneous soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Electrical resistivity (ER) sounding is increasingly being used as non-invasive technique to reveal and map soil heterogeneity. The objective of this work was to assess ER sounding applicability to study soil water distribution in spatially heterogeneous soils. The 30x30-m study plot was located at ...

  5. Ready Contents or Future Skills? A Comparative Study of Teacher Education in Thailand and Finland

    ERIC Educational Resources Information Center

    Vibulphol, Jutarat; Loima, Jyrki; Areesophonpichet, Sornnate; Rukspollmuang, Chanita

    2015-01-01

    This study aimed to analyze the recently updated teacher education programmes in two universities in Finland and Thailand. The article reports the characteristics of the elementary and secondary school teacher education studies in the selected universities, and discusses the roles and significance of 21st century skills and their modifications in…

  6. Content Analysis of Jordanian Elementary Textbooks during 1970-2013 as Case Study

    ERIC Educational Resources Information Center

    Abed, Eman Rasmi; Al-Absi, Mohammad Mustafa

    2015-01-01

    This study aims to determine types of mathematic disciplines (in term of topics) in Jordanian Elementary textbooks. This study evaluates mathematics text books especially in the period between 1970 and 2013 and identifies types and quantities of mathematics. To examine the relative quantity of mathematics, branches of mathematics, presentation…

  7. Teaching Cause-Effect Text Structure through Social Studies Content to At-Risk Second Graders

    ERIC Educational Resources Information Center

    Williams, Joanna P.; Nubla-Kung, Abigail M.; Pollini, Simonne; Stafford, K. Brooke; Garcia, Amaya; Snyder, Anne E.

    2007-01-01

    This study evaluated the effectiveness of a comprehension program integrated with social studies instruction designed for at-risk second graders. The program included instruction in cause-effect text structure, emphasizing clue words, generic questions, graphic organizers, and the close analysis of specially constructed cause-effect target…

  8. A Content Literacy Collaborative Study Group: High School Teachers Take Charge of Their Professional Learning

    ERIC Educational Resources Information Center

    Thibodeau, Gail M.

    2008-01-01

    The progress and effects of a collaborative study group as a method of job-embedded professional development were studied. Eight high school teachers representing a variety of disciplines and the author (a literacy specialist) met monthly as a collaborative group for one school year to investigate materials and methods for literacy strategy…

  9. Computer Literacy and Social Studies Teacher Education: Changes in Form and Content.

    ERIC Educational Resources Information Center

    Napier, John D.

    The impact of teaching computer literacy on the social studies curriculum, instruction, and teacher education is discussed. Social studies computer literacy objectives are organized into three components: awareness, understanding how computer technology affects individuals and society; acquisition, knowing how computers work and how to operate a…

  10. Content Analysis of the Studies in Turkey on the Ability of Critical Thinking

    ERIC Educational Resources Information Center

    Polat, Seyat

    2015-01-01

    Critical thinking, along with other skills, is included as a basic skill in the constructive education program that has been in use in Turkey since 2005. Therefore, a large increase has been observed in studies on critical thinking skills since 2005. In this frame, the present study was conducted in order to systematically examine research papers…

  11. 7 CFR 4280.176 - Feasibility study grant applications-content.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Energy for America Program General Renewable Energy System Feasibility Study Grants § 4280.176... renewable energy system. (10) If the applicant is a rural small business, certification that the feasibility study grant will be for a renewable energy system project that is located in a rural area. (11)...

  12. 7 CFR 4280.176 - Feasibility study grant applications-content.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Energy for America Program General Renewable Energy System Feasibility Study Grants § 4280.176... renewable energy system. (10) If the applicant is a rural small business, certification that the feasibility study grant will be for a renewable energy system project that is located in a rural area. (11)...

  13. Exploring Cultural Content of Three Prominent EFL Textbooks in Iran (A Case Study of American English Files, Top Notch and Four Corners)

    ERIC Educational Resources Information Center

    Dehbozorgi, Mehrnoosh; Amalsaleh, Ehya; Kafipour, Reza

    2014-01-01

    Cultural content has become an important issue after the advent of intercultural communicative approach (ICC) in language teaching field. The current study analyzed cultural content of three mainstream intermediate level EFL textbooks. This study was carried out using Chen's (2004) and Lee's (2009) suggested themes for detecting big "C"…

  14. A Long Term Study of the Water Content Changes in Three Types of Hydrogel Contact Lenses.

    DTIC Science & Technology

    1987-05-01

    in visual acuity , keratometric readings, and post-lens removal refractions? Appropriate statistical analysis of the data would be used to determine the...study. Visual acuities had to be correctable to 20/20 or better in each eye by both spectacles and contact lens. Participation in this study required...eye. This was done before and after lens removal. 4. Distant Snellen visual acuity --measured through contact lenses with a • -: Meanco projector and an

  15. In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

    PubMed Central

    Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

    2009-01-01

    During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

  16. Digital immigrants teaching digital natives: A phenomenological study of higher education faculty perspectives on technology integration with English core content

    NASA Astrophysics Data System (ADS)

    Corey, Robert C.

    In the last two decades, technology use has escalated and educators grapple with its advances and integration into the classroom. Issues surrounding what constitutes a literate society, the clarion calls for educational reform emanating from US presidents to parent teacher organizations, and educators' ability to cope with advances in technology in the classroom demand attention. Therefore, the purpose of this qualitative study was to explore and understand the professional and educational experiences of six English faculty members teaching undergraduate courses at Midwest universities. Using the framework of Technological Pedagogical Content Knowledge -- TPACK (Koehler and Mishra 2008), the major focus of the study was to determine how faculty members understood what characterized the nature of teaching with technology in undergraduate classrooms. Results of this study revealed five themes showing how the participants were introduced to technology, how they assimilated it into their pedagogy, and how they integrated it into teaching practice. This study has the potential to impact the nature of illustrating the methods and techniques used by the six participants as they merge technology, pedagogy, and content knowledge and set in motion classroom practices that assist faculty at all levels to develop and teach technology skills necessary for the 21st century and to better prepare students for thinking critically about how to use digital advances.

  17. Content Wizard.

    ERIC Educational Resources Information Center

    Ehlers-Zavala, Fabiola P.

    2001-01-01

    This classroom tip focuses on sustained-content language teaching. The game described--content wizard-- illustrates a practical technique for incorporating a range of language and academic skills into subject matter lessons for English-as-a-Second-Language learners. (Author/VWL)

  18. MONITOR Ionospheric Network: two case studies on scintillation and electron content variability

    NASA Astrophysics Data System (ADS)

    Béniguel, Yannick; Cherniak, Iurii; Garcia-Rigo, Alberto; Hamel, Pierrick; Hernández-Pajares, Manuel; Kameni, Roland; Kashcheyev, Anton; Krankowski, Andrzej; Monnerat, Michel; Nava, Bruno; Ngaya, Herbert; Orus-Perez, Raül; Secrétan, Hughes; Sérant, Damien; Schlüter, Stefan; Wilken, Volker

    2017-03-01

    The ESA MONITOR network is composed of high-frequency-sampling global navigation satellite systems (GNSS) receivers deployed mainly at low and high latitudes to study ionosphere variability and jointly with global GNSS data and ionospheric processing software in support of the GNSS and its satellite-based augmentation systems (SBAS) like the European EGNOS. In a recent phase of the project, the network was merged with the CNES/ASECNA network and new receivers were added to complement the latter in the western African sector. This paper summarizes MONITOR, presenting two case studies on scintillations (using almost 2 years of data measurements). The first case occurred during the major St. Patrick's Day geomagnetic storm in 2015. The second case study was performed in the last phase of the project, which was supported by ESA EGNOS Project Office, when we paid special attention to extreme events that might degrade the system performance of the European EGNOS.

  19. Review of simulation studies in anaesthesia journals, 2001-2010: mapping and content analysis.

    PubMed

    Ross, A J; Kodate, N; Anderson, J E; Thomas, L; Jaye, P

    2012-07-01

    Despite widespread adoption of simulation-based training in medical education, there remains scepticism about its cost-effectiveness and long-term impact on patient outcomes. Medical simulation is well established in anaesthesia where it is considered an important educational tool. This review of key clinical anaesthesia literature is used as a case study of clinician uptake within a specialty and to investigate evidence for translational impact using both qualitative and quantitative data. We examined high-impact journal publications from 2001 to 2010 and extracted data covering authors, institutions, simulation modality, purposes of simulation, and various aspects of study design/methodology used. A total of 320 papers containing primary data were included. We found broad acceptance and uptake in anaesthesia with an increase in publications over the time period, mainly attributable to a steady increase in manikin studies. Studies using manikin technology (130/320; 41%) are distinguished as skills/performance studies (76; 58%) and studies focused on the use, testing, and validation of equipment (52; 40%). A total of 110 papers (34%) assessed the performance of technical and non-technical skills (68% and 32%, respectively). Growth in the use of structured checklists/validated tools to assess performance is mainly observed in the non-technical domain. Only 10% of these papers include follow-up data from the clinical environment. There is a lack of research examining performance transfer, sustainability, and direct patient outcomes and experiences. These publication patterns are instructive for those involved in medical educational and for other clinical specialties developing simulation.

  20. Spinal palpatory diagnostic procedures utilized by practitioners of spinal manipulation: annotated bibliography of content validity and reliability studies

    PubMed Central

    Seffinger, Michael; Adams, Alan; Najm, Wadie; Dickerson, Vivian; Mishra, Shiraz I; Reinsch, Sibylle; Murphy, Linda

    2003-01-01

    The diagnosis of spinal neuro-musculoskeletal dysfunction is a pre-requisite for application of spinal manual therapy. Different disciplines rely on palpatory procedures to establish this diagnosis and design treatment plans. Over the past 30 years, the osteopathic, chiropractic, physical therapy and allopathic professions have investigated the validity and reliability of spinal palpatory procedures. We explored the literature from all four disciplines looking for scientific papers studying the content validity and reliability of spinal palpatory procedures. Thirteen databases were searched for relevant papers between January 1966 and October 2001. An annotated bibliography of these articles is presented and organized by the type of test used.

  1. Content Analysis of Memory and Memory-Related Research Studies on Children with Hearing Loss

    ERIC Educational Resources Information Center

    Dogan, Murat; Hasanoglu, Gülcihan

    2016-01-01

    Memory plays a profound role in explaining language development, academic learning, and learning disabilities. Even though there is a large body of research on language development, literacy skills, other academic skills, and intellectual characteristics of children with hearing loss, there is no holistic study on their memory processes.…

  2. Gender Differences in the Content of Preschool Children's Recollections: A Longitudinal Study

    ERIC Educational Resources Information Center

    Tõugu, Pirko; Tulviste, Tiia; Suits, Kristi

    2014-01-01

    Personal recollections constitute autobiographical memory that develops intensively during the preschool years. The two-wave longitudinal study focuses on gender differences in preschool children's independent recollections. The same children (N = 275; 140 boys, 135 girls) were asked to talk about their previous birthday and the past weekend at…

  3. A Content Analysis of the TEFL M.A. Entrance Examinations (Case Study: Majors Courses)

    ERIC Educational Resources Information Center

    Razmjoo, Seyyed Ayatollah; Heydari Tabrizi, Hossein

    2010-01-01

    The MA Entrance Examinations (MAEE) held in Iran since 1990 are frequently criticized as being invalid, unstandardized exams with lots of problem in terms of principles of testing in general and test construction in particular (for instance, Jafarpur, 1996). To make sound judgments about such objections, the present study dealt with a content…

  4. Colorado Teen Challenges and Choices Curriculum State Content Standards for Consumer & Family Studies.

    ERIC Educational Resources Information Center

    Bohlender, Pat; Calhoun, Peggy; Goemer, Phil; Inman, Sondra; Kilgore, Cherryl; McManigal, Lori; Neergaard, Hope; Peppler, Colleen; Wateman, Linda

    This document presents materials and guidelines for evaluating Colorado high school students' attainment of the eight state standards for consumer and family studies that pertain to teen challenges and choices. The materials presented are designed to promote and evaluate students' mastery of the following competencies: (1) examine and demonstrate…

  5. The Recurring Author: William Shakespeare, a Case Study through Content Analysis.

    ERIC Educational Resources Information Center

    Harrison, Robert L., Jr.

    The "recurring author" is one whose works appear many times at different levels in instructional units found in literature textbook series. A descriptive case study discussed the treatment of a recurring author, William Shakespeare, using units in a sample of six literature textbook series. Developed to describe, to code, and to analyze…

  6. Gender Equality in Media Content and Operations: Articulating Academic Studies and Policy--A Presentation

    ERIC Educational Resources Information Center

    Lourenço, Mirta Edith

    2016-01-01

    In this article, Mirta Lourenço explains the prospects when higher education studies interface with UNESCO for policy change. The baseline is that education institutions' articulation with media organizations, media professionals, policy-makers, and civil society groups is essential to achieve gender equality in and through media.

  7. Linguistic Indices of Deception as Manifested by Women: A Content Analytic Study.

    ERIC Educational Resources Information Center

    Mancillas, William R. Todd; Kibler, Robert J.

    Recent research indicates that fourteen linguistic and paralinguistic patterns--thought to measure uncertainty, vagueness, dependence, and negative affect--discriminate between men's truth telling and deceptive language behavior. This study sought to determine if these same patterns also discriminate between women's truth telling and deceptive…

  8. Directing Curriculum through Standards: A Content Analysis of the 2010 Texas State Social Studies Standards

    ERIC Educational Resources Information Center

    Smith, Norman

    2012-01-01

    In 2010 the Texas Education Agency adopted newly rewritten curriculum standards for the state's social studies courses K-12. The period leading up to the adoption of the standards proved contentious as the new standards moved out of the writing committees and into the public realm. The issues brought forth from initial readings of the standards…

  9. Classification of Professional Values Based on Motivational Content: An Exploratory Study on Italian Adolescents

    ERIC Educational Resources Information Center

    Pallini, Susanna; Bove, Giuseppe; Laghi, Fiorenzo

    2011-01-01

    This study applies a multidimensional scaling (MSD) technique to investigate the structural validity of the Work Values Inventory for Adolescents with a sample of Italian students. The MSD results indicated the presence of two underlying orthogonal dimensions: individuality versus sociality and conservation versus exploration. Implications for…

  10. Probing Student Teachers' Subject Content Knowledge in Chemistry: Case Studies Using Dynamic Computer Models

    ERIC Educational Resources Information Center

    Toplis, Rob

    2008-01-01

    This paper reports case study research into the knowledge and understanding of chemistry for six secondary science student teachers. It combines innovative student-generated computer animations, using "ChemSense" software, with interviews to probe understanding of four common chemical processes used in the secondary school curriculum. Findings…

  11. Methodological Study for Determining the Task Content of Dental Auxiliary Education Programs. Progress Report.

    ERIC Educational Resources Information Center

    Terry, David R.

    The purpose of the study was to develop a methodology of collecting data pertaining to the dental tasks taught and the responsibility levels to which they are taught in the curricula of educational institutions preparing dental assistants, hygienists, and laboratory technicians. The sample group consisted of Faculty and Preceptor respondents from…

  12. Determination of the total nitrogen content of hard, semihard, and processed cheese by the Kjeldahl method: collaborative study.

    PubMed

    Lynch, Joanna M; Barbano, David M; Fleming, J Richard

    2002-01-01

    The objective of this collaborative study was to determine interlaboratory performance statistics for a modified and optimized version of AOAC Method 920.123 for the determination of the total nitrogen content of hard, semihard, and processed cheese by Kjeldahl analysis. Details included addressing the issues of material homogeneity, test portion size (1 g), quantitative transfer (weighing on to filter paper), ensuring system suitability (nitrogen recoveries), and using AOAC Method 991.20 as the basis for nitrogen analysis. Fifteen laboratories tested 18 pairs of blind duplicate cheese materials with a crude protein content between 18 and 36%. Materials represented hard, semihard, and processed commercial cheeses with a wide range of composition. Statistical performance parameters expressed as crude protein (nitrogen x 6.38), g/100 g, with invalid and outlier data removed were mean = 26.461, repeatability standard deviation (Sr) 0.111, reproducibility standard deviation (S(R)) = 0.153, repeatability relative standard deviation (RSDr) = 0.42%, reproducibility relative standard deviation (RSDR) = 0.58%, repeatability (r) = 0.312, and reproducibility (R) = 0.428. The interlaboratory study results were acceptable and comparable to those for the milk Kjeldahl nitrogen method on a relative nitrogen basis. The Study Directors recommend that this modified method for the determination of total nitrogen in hard, semihard, and processed cheese by Kjeldahl analysis be adopted First Action as an improved method to replace Method 920.123.

  13. [Importance of studying the balance of vaginal content (BAVACO) in the preventive control of sex workers].

    PubMed

    Bologno, Romina; Díaz, Yanina M; Giraudo, María C; Fernández, Rosa; Menéndez, Viviana; Brizuela, Juan C; Gallardo, Adriana A; Alvarez, Laura A; Estevao Belchior, Silvia G

    2011-01-01

    The aim of this work was to study the vaginal microenvironment in sex workers from Comodoro Rivadavia, Chubut. For that purpose, BAVACO procedures were applied. A total of 229 female sex workers attended public health centers. Vaginal secretions were analyzed by Gram and Giemsa stains. The following results were obtained: normal microbiota 35.37 %, intermediate microbiota 15.72 %, bacterial vaginosis 23.14 %, microbial non-specific vaginitis, Donders'"aerobic vaginitis" 10.48 %, yeast vulvovaginitis 8.30 %, and trichomoniasis 6.99 %. The intermediate microbiota was characterized by a decrease in the number of lactobacilli and the presence of diphtheroid bacilli cell types. The population studied shared increased values of vaginal dysfunctions. These results are considered risk factors for obstetric and gynecologic diseases.

  14. Study of contents of 226Ra, 232Th and 40K in fertilisers.

    PubMed

    Tahir, S N A; Alaamer, A S; Omer, R M

    2009-02-01

    In this study concentrations of naturally occurring radionuclides (226)Ra, (232)Th and (40)K were measured in the fertiliser samples in Pakistan using a high-resolution and high-purity germanium detector. Samples were collected from main fertiliser depots located in 10 big cities in the Punjab province. Gamma spectrometric analysis revealed that concentrations of (226)Ra, (232)Th and (40)K existed in the ranges from 232 to 511 Bq kg(-1), 21 to 58 Bq kg(-1) and 556 to 1302 Bq kg(-1) with average values of 386 +/- 92, 38 +/- 14 and 885 +/- 220 Bq kg(-1), respectively. Average values of the three natural radionuclides measured in this study were within the range of reported values from some of the other countries of the world. Correlations drawn between measured concentrations were not significant.

  15. A Case Study on Content Based Instruction for Primary School Children

    ERIC Educational Resources Information Center

    Hidalgo Dávila, Helda Alicia; Caucedo Vela, Magda Lucy

    2011-01-01

    Teaching English at the primary school level is a challenge in countries such as Colombia where children study this language for only one hour a week in most institutions, and in the best of cases for 3 hours a week. Most of the public schools do not have enough and/or adequate English materials at their disposal for students to work with;…

  16. Comparative study of volatile oil content and antimicrobial activity of pecan cultivars growing in Egypt.

    PubMed

    El Hawary, Seham S; Zaghloul, Soumaya S; El Halawany, Ali M; El Bishbishy, Mahitab H

    2013-11-01

    The volatile oils obtained from the leaves of four pecan cultivars growing in Egypt were evaluated for their chemical composition and antimicrobial activity. The selected cultivars (cv.) were Carya illinoinensis (Wangneh.) K. Koch. cv. Wichita, C. illinoinensis cv. Western Schley, C. illinoinensis cv. Cherokee, and C. illinoinensis cv. Sioux. The gas chromatography-mass spectrometry analyses revealed that the volatile oils from samples of the different cultivars differ in composition and percentage of their components. β-Curcumene was found as the major constituent of the cv. Wichita oil, whereas germacrene D was the major component of cv. Sioux, cv. Cherokee, and cv. Western Schley. The antimicrobial activity was assayed using the Kirby-Bauer Method by measuring the zone of inhibition of growth. All volatile oils displayed an antimicrobial activity against the tested bacterial strains. On the other hand, only the volatile oil of cv. Wichita showed an antifungal effect on Aspergillus flavus. This work has identified candidates of volatile oils for future in vivo studies to develop antibiotic substitutes for the diminution of human and animal pathogenic bacteria. Nevertheless, the variations of the volatile oil components and antimicrobial potencies of the different studied cultivars, necessitate identifying the cultivars used in future studies.

  17. Meta-Study as Diagnostic: Toward Content Over Form in Qualitative Synthesis.

    PubMed

    Frost, Julia; Garside, Ruth; Cooper, Chris; Britten, Nicky

    2016-02-01

    Having previously conducted qualitative syntheses of the diabetes literature, we wanted to explore the changes in theoretical approaches, methodological practices, and the construction of substantive knowledge which have recently been presented in the qualitative diabetes literature. The aim of this research was to explore the feasibility of synthesizing existing qualitative syntheses of patient perspectives of diabetes using meta-study methodology. A systematic review of qualitative literature, published between 2000 and 2013, was conducted. Six articles were identified as qualitative syntheses. The meta-study methodology was used to compare the theoretical, methodological, analytic, and synthetic processes across the six studies, exploring the potential for an overarching synthesis. We identified that while research questions have increasingly concentrated on specific aspects of diabetes, the focus on systematic review processes has led to the neglect of qualitative theory and methods. This can inhibit the production of compelling results with meaningful clinical applications. Although unable to produce a synthesis of syntheses, we recommend that researchers who conduct qualitative syntheses pay equal attention to qualitative traditions and systematic review processes, to produce research products that are both credible and applicable.

  18. Australian seafood compositional profiles: A pilot study. Vitamin D and mercury content.

    PubMed

    Padula, David; Greenfield, Heather; Cunningham, Judy; Kiermeier, Andreas; McLeod, Catherine

    2016-02-15

    Given the scarcity of comprehensive nutritional data for Australia's >400 commercially produced seafood species a pilot study was undertaken to collect and analyse 22 species of wild and aquaculture seafood in order to develop a model for future comprehensive surveys. The species analysed were: Atlantic salmon, Australian sardine, prawn (six species), barramundi, abalone (three species), blue sprat, burrowing blackfish, gummy shark, oyster (four species), ocean trout and yellowtail kingfish. The analyses undertaken in this pilot study were: moisture, protein, total fat, cholesterol, fatty acids, vitamin C, vitamins A and D, and 21 mineral elements (including total mercury and methyl mercury). The data reported here are for vitamin D and mercury only. Comprehensive data have already been published elsewhere. Issues identified that should be addressed prior to undertaking a more extensive and representative study of the remaining major edible commercial Australian seafood species include: choice of samples and nutrients for analysis, facilities for sample handling and storage, data management and scrutiny, and laboratory quality control.

  19. Study on the Relationship between the Depth of Spectral Absorption and the Content of the Mineral Composition of Biotite.

    PubMed

    Yang, Chang-bao; Zhang, Chen-xi; Liu, Fang; Jiang, Qi-gang

    2015-09-01

    The mineral composition of rock is one of the main factors affecting the spectral reflectance characteristics, and it's an important reason for generating various rock characteristic spectra. This study choose the rock samples provided by Jet Propulsion Laboratory (JPL) (including all kinds of mineral percentage of rocks, and spectral reflectances range from 0.35 to 2.50 μm wavelength measured by ASD spectrometer), and the various types of mineral spectral reflectances contained within the rocks are the essential data. Using the spectral linear mixture model of rocks and their minerals, firstly, a simulation study on the mixture of rock and mineral composition is achieved, the experimental results indicate that rock spectral curves using the model which based on the theory of the linear mixture are able to simulate better and preserve the absorption characteristics of various mineral components well. Then, 8 samples which contain biotite mineral are picked from the rock spectra of igneous, biotite contents and the absorption depth characteristics of spectral reflection at 2.332 μm, furthermore, a variety of linear and nonlinear normal statistical models are used to fit the relationship between the depth of absorption spectra and the content of the mineral composition of biotite, finally, a new simulation model is build up with the Growth and the Exponential curve model, and a statistical response relationship between the spectral absorption depth and the rock mineral contents is simulated by using the new model, the fitting results show that the correlation coefficient reaches 0.9984 and the standard deviation is 0.572, although the standard deviation using Growth and Exponential model is less than the two model combined with the new model fitting the standard deviation, the correlation coefficient of the new model had significantly increased, which suggesting that the, new model fitting effect is closer to the measured values of samples, it proves that the

  20. The role of β-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome

    PubMed Central

    Wisler, James W.; Harris, Emily M.; Raisch, Michael; Mao, Lan; Kim, Jihee; Rockman, Howard A.

    2015-01-01

    Ang II type 1a receptor (AT1aR)-mediated activation of MAPKs contributes to thoracic aortic aneurysm (TAA) development in Marfan syndrome (MFS). β-Arrestin2 (βarr2) is known to mediate AT1aR-dependent MAPK activation, as well as proproliferative and profibrotic signaling in aortic vascular smooth muscle cells. Therefore, we investigated whether βarr2-dependent signaling contributes to TAA formation in MFS. We used a murine model of MFS [fibrillin (Fbn)C1039G/+] to generate an MFS murine model in combination with genetic βarr2 deletion (FbnC1039G/+/βarr2−/−). FbnC1039G/+/βarr2−/− mice displayed delayed aortic root dilation compared with FbnC1039G/+ mice. The mRNA and protein expression of several mediators of TAA formation, including matrix metalloproteinase (MMP)-2 and -9, was reduced in the aorta of FbnC1039G/+/βarr2−/− mice relative to FbnC1039G/+ mice. Activation of ERK1/2 was also decreased in the aortas of FbnC1039G/+/βarr2−/− mice compared with FbnC1039G/+ animals. Small interfering RNA targeting βarr2 inhibited angiotensin-stimulated expression of proaneurysmal signaling mediators in primary aortic root smooth muscle cells. Angiotensin-stimulated expression of the proaneurysmal signaling mediators MMP-2 and -9 was inhibited by blockade of ERK1/2 or the EGF receptor, whereas blockade of the transforming growth factor-β receptor had no effect. These results suggest that βarr2 contributes to TAA formation in MFS by regulating ERK1/2-dependent expression of proaneurysmal genes and proteins downstream of the AT1aR. Importantly, this demonstration of the unique signaling mechanism by which βarr2 contributes to aneurysm formation identifies multiple novel, potential therapeutic targets in MFS. PMID:26371162