bluuebunny/crossref_metadata_2025_split huggingface dataset:
A preliminary validation of Attention, Relevance, Confidence and Satisfaction model‐based Instructional Material Motivational Survey in a computer‐based tutorial setting
Authors: Huang Wenhao , Huang Wenyeh , Diefes‐Dux Heidi , Imbrie Peter K. 
Published: December 2005

AbstractThis paper describes a preliminary validation study of the Instructional Material Motivational Survey (IMMS) derived from the Attention, Relevance, Confidence and Satisfaction motivational design model. Previous studies related to the IMMS, however, suggest its practical application for motivational evaluation in various instructional settings without the support of empirical data. Moreover, there is a lack of discussion regarding the validity of the instrument. Therefore, this study empirically examined the IMMS as a motivational evaluation instrument. A computer‐based tutorial setting was selected owing to its wide application in teaching large entry‐level college courses. Data collected from 875 subjects were subjected to exploratory and confirmatory factor analyses, and measurement modelling LISREL. Findings suggested that 16 original items should be excluded from the IMMS; the retained 20 items were found to fall into different constructs, indicating that instructional features of the tutorial may influence the validity of the survey items. The implication of the study supports the situational  feature  of  the  IMMS.  Therefore,  a  preevaluation  adjustment  on the IMMS items is recommended to identify suitable items before the full motivational evaluation. Future research should focus on the further validation of the IMMS based on this preliminary evidence.
An event‐related potential study on the “check operation” in the Eriksen task1
Authors: IWAKI NOBUYOSHI , MIYATANI MAKOTO , TOSHIMA TAMOTSU 
Published: December 2005

Abstract:  We examined two issues for the Eriksen task with two types of stimuli, the central target letter of which was flanked with noise (e.g., HHHHH for compatible stimuli and SSHSS for incompatible stimuli). First, we examined whether or not a response‐stop function is carried out until the check operation to detect and correct erroneous response readiness has finished (Eriksen & Eriksen, 1974). Second, reaction times for incompatible stimuli are not prolonged if only identical noise stimuli are used throughout the block. This phenomenon is called the blocking effect. We then explored whether or not the blocking effect can be caused by the selective inhibition of erroneous response readiness (Eriksen & Schultz, 1979). Sixteen participants (18–29 years old) selectively pressed one of two buttons for the target letter. The results showed that the negative potential related to the response‐stop function was enlarged for incompatible stimuli. Moreover, the blocking effect was observed, while erroneous response readiness was still observable for incompatible stimuli. These results suggest that the blocking effect is caused by something other than reciprocal inhibition.
Effect of the A118G polymorphism on binding affinity, potency and agonist‐mediated endocytosis, desensitization, and resensitization of the human mu‐opioid receptor
Authors: Beyer Andrea , Koch Thomas , Schröder Helmut , Schulz Stefan , Höllt Volker 
Published: December 2005

AbstractThe most prevalent single‐nucleotide polymorphism (SNP) A118G in the human µ‐opioid receptor gene predicts an amino acid change from an asparagine residue to an aspartatic residue in amino acid position 40. This N40D mutation, which has been implicated in the development of opioid addiction, was previously reported to result in an increased β‐endorphin binding affinity and a decreased potency of morphine‐6‐glucuronide. Therefore, in the present study we have investigated whether this mutation might affect the binding affinity, potency, and/or the agonist‐induced desensitization, internalization and resensitization of the human µ‐opioid receptor stably expressed in human embryonic kidney 293 cells. With the exception of a reduced expression level of N40D compared to human µ‐opioid receptor (hMOR) in HEK293 cells, our analyses revealed no marked functional differences between N40D and wild‐type receptor. Morphine, morphine‐6‐glucuronide and β‐endorphin revealed similar binding affinities and potencies for both receptors. Both the N40D‐variant receptor and hMOR exhibited robust receptor internalization in the presence of the opioid peptide [d‐Ala2,N‐MePhe4,Glyol5]enkephalin (DAMGO) and β‐endorphin but not in response to morphine or morphine‐6‐glucuronide. After prolonged treatment with morphine, morphine‐6‐glucuronide or β‐endorphin both receptors showed similiar desensitization time courses. In addition, the receptor resensitization rates were nearly identical for both receptor types.
The cloning and characterization of a second brain enzyme with NAAG peptidase activity
Authors: Bzdega Tomasz , Crowe Samantha L. , Ramadan Epolia R. , Sciarretta Kathryn H. , Olszewski Rafal T. , Ojeifo Olumide A. , Rafalski Victoria A. , Wroblewska Barbara , Neale Joseph H. 
Published: December 2005

AbstractThe peptide neurotransmitterN‐acetylaspartylglutamate is inactivated by extracellular peptidase activity following synaptic release. It is speculated that the enzyme, glutamate carboxypeptidase II (GCPII, EC 3.14.17.21), participates in this inactivation. However, CGCPII knockout mice appear normal in standard neurological tests. We report here the cloning and characterization of a mouse enzyme (tentatively identified as glutamate carboxypeptidase III or GCPIII) that is homologous to an enzyme identified in a human lung carcinoma. The mouse peptidase was cloned from two non‐overlapping EST clones and mouse brain cDNA using PCR. The sequence (GenBank,AY243507) is 85% identical to the human carcinoma enzyme and 70% homologous to mouse GCPII. GCPIII sequence analysis suggests that it too is a zinc metallopeptidase. Northern blots revealed message in mouse ovary, testes and lung, but not brain. Mouse cortical and cerebellar neurons in culture expressed GCPIII message in contrast to the glial specific expression of GCPII. Message levels of GCPIII were similar in brains obtained from wild‐type mice and mice that are null mutants for GCPII. Chinese hamster ovary (CHO) cells transfected with rat GCPII or mouse GCPIII expressed membrane bound peptidase activity with similarVmaxandKmvalues (1.4 µmand 54 pmol/min/mg; 3.5 µmand 71 pmol/min/mg, respectively). Both enzymes are activated by a similar profile of metal ions and their activities are blocked by EDTA. GCPIII message was detected in brain and spinal cord by RT‐PCR with highest levels in the cerebellum and hippocampus. These data are consistent with the hypothesis that nervous system cells express at least two differentially distributed homologous enzymes with similar pharmacological properties and affinity for NAAG.
Serotoninergic neurotransmission is affected by n‐3 polyunsaturated fatty acids in the rat
Authors: Kodas Ercem , Galineau Laurent , Bodard Sylvie , Vancassel Sylvie , Guilloteau Denis , Besnard Jean‐Claude , Chalon Sylvie 
Published: December 2005

AbstractWe explored the effects of chronic α‐linolenic acid dietary deficiency on serotoninergic neurotransmission. In vivo synaptic serotonin (5‐HT) levels were studied in basal and pharmacologically stimulated conditions using intracerebral microdialysis in the hippocampus of awake 2‐month‐old rats. We also studied the effects of reversion of the deficient diet on fatty acid composition and serotoninergic neurotransmission. A balanced (control) diet was supplied to deficient rats at different stages of development, i.e. from birth, 7, 14 or 21 days of age. We demonstrated that chronic n‐3 polyunsaturated fatty acid dietary deficiency induced changes in the synaptic levels of 5‐HT both in basal conditions and after pharmacological stimulation with fenfluramine. Higher levels of basal 5‐HT release and lower levels of 5‐HT‐stimulated release were found in deficient than in control rats. These neurochemical modifications were reversed by supply of the balanced diet provided at birth or during the first 2 weeks of life through the maternal milk, whereas they persisted if the balanced diet was given from weaning (at 3 weeks of age). This suggests that provision of essential fatty acids is durably able to affect brain function and that this is related to the developmental stage during which the deficiency occurs.
Brevetoxin activation of voltage‐gated sodium channels regulates Ca2+dynamics and ERK1/2 phosphorylation in murine neocortical neurons
Authors: Dravid Shashank M. , Baden Daniel G. , Murray Thomas F. 
Published: December 2005

AbstractVoltage‐gated sodium channels (VGSC) are involved in the generation of action potentials in neurons. Brevetoxins (PbTx) are potent allosteric enhancers of VGSC function and are associated with the periodic ‘red tide’ blooms. Using PbTx‐2 as a probe, we have characterized the effects of activation of VGSC on Ca2+dynamics and extracellular signal‐regulated kinases 1/2 (ERK1/2) signaling in neocortical neurons. Neocortical neurons exhibit synchronized spontaneous Ca2+oscillations, which are mediated by glutamatergic signaling. PbTx‐2 (100 nm) increased the amplitude and reduced the frequency of basal Ca2+oscillations. This modulatory effect on Ca2+oscillations produced a sustained rise in ERK1/2 activation. At 300 nm, PbTx‐2 disrupted oscillatory activity leading to a sustained increase in intracellular Ca2+([Ca2+]i) and induced a biphasic, activation followed by dephosphorylation, regulation of ERK1/2. PbTx‐2‐induced ERK1/2 activation was Ca2+dependent and was mediated by Ca2+entry through manifold routes. PbTx‐2 treatment also increased cAMP responsive element binding protein (CREB) phosphorylation and increased gene expression of brain‐derived neurotrophic factor (BDNF). These findings indicate that brevetoxins, by influencing the activation of key signaling proteins, can alter physiologic events involved in survival in neocortical neurons, as well as forms of synaptic plasticity associated with development and learning.
Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone‐glial related cell adhesion molecule
Authors: Davey Fleur , Hill Maria , Falk Julien , Sans Nathalie , Gunn‐Moore Frank J. 
Published: December 2005

AbstractNeurone glial‐related cell adhesion molecule (NrCAM) is a member of the L1 family of transmembrane cell adhesion receptors which are involved in the development and function of the mammalian nervous system. How these receptors interact with intracellular signalling pathways is not understood. To date the only identified binding partner to the cytoplasmic terminus of NrCAM is ankyrin G. We screened a developing rat brain cDNA yeast two‐hybrid library with the cytoplasmic domain of NrCAM to identify further intracellular binding partners. We identified synapse associated protein 102 (SAP102) as a new binding partner for NrCAM. The interaction was confirmed biochemically using glutathione S‐transferase (GST)‐pull‐down and tandem affinity purification, and also immunocytochemically as NrCAM and SAP102 co‐localized in COS‐7 and cerebellar granule cells. Binding was specific to NrCAM as neither neurofascin nor L1 bound SAP102, and this interaction was reliant on the last three amino acids of NrCAM. Additionally, NrCAM constructs whose last three amino acids had been deleted appeared to have a dominant negative effect on neurite extension of cerebellar granule cells. This is the first interaction reported for NrCAM, and its association with SAP102 suggests that it is part of a larger complex which can interact with many different signalling pathways.
Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and γ‐secretase activity
Authors: Brunkan A. L. , Martinez M. , Wang J. , Walker E. S. , Beher D. , Shearman M. S. , Goate A. M. 
Published: December 2005

AbstractPresenilins (PS) are thought to contain the active site for presenilinase endoproteolysis of PS and γ‐secretase cleavage of substrates. The structural requirements for PS incorporation into the γ‐secretase enzyme complex, complex stability and maturation, and appropriate presenilinase and γ‐secretase activity are poorly understood. We used rescue assays to identify sequences in transmembrane domain one (TM1) of PS1 required to support presenilinase and γ‐secretase activities. Swap mutations identified an N‐terminal TM1 domain that is important for γ‐secretase activity only and a C‐terminal TM1 domain that is essential for both presenilinase and γ‐secretase activities. Exchange of residues 95–98 of PS1 (sw95–98) completely abolishes both activities while the familial Alzheimer's disease mutation V96F significantly inhibits both activities. Reversion of residue 96 back to valine in the sw95–98 mutant rescues PS function, identifying V96 as the critical residue in this region. The TM1 mutants do not bind to an aspartyl protease transition state analog γ‐secretase inhibitor, indicating a conformational change induced by the mutations that abrogates catalytic activity. TM1 mutant PS1 molecules retain the ability to interact with γ‐secretase substrates and γ‐secretase complex members, although Nicastrin stability is decreased by the presence of these mutants. γ‐Secretase complexes that contain V96F mutant PS1 molecules display a partial loss of function for γ‐secretase that alters the ratio of amyloid‐β peptide species produced, leading to the amyloid‐β peptide aggregation that causes familial Alzheimer's disease.
Somatostatin and the somatostatin receptor 2 are reciprocally controlled by calcineurin during cerebellar granule cell maturation
Authors: Kramer Dana , Caruso Alessandra , Nicoletti Ferdinando , Genazzani Armando A. 
Published: December 2005

AbstractActivity‐dependent Ca2+ influx into neurones and the subsequent changes in gene expression are thought to be important in shaping neuronal development. In this study, we investigated whether an important mediator of neuronal migration, somatostatin (Srif), alongside its receptors, is controlled in this manner in cerebellar granule cells. We show that Ca2+ influx increases the expression of somatostatin mRNA (srif), while somatostatin receptor 2 (sst2) mRNA expression is decreased. Both genes appear to be regulated independently of each other and in a calcineurin‐dependent manner that does not depend on either the ERK1/2 MAP kinase or the cAMP/CREB pathway. Nonetheless, a second pathway is required to induce changes in srif and sst2 expression, since constitutively active calcineurin alone is not sufficient to induce these changes. Furthermore, calcineurin activation reciprocally regulates the expression of brain‐derived neurotrophic factor, bdnf, and its receptor trkb, which have also been shown to play a role in neuronal migration. Finally, calcineurin appears to control the expression of the neuronal marker transient axonal glycoprotein 1, tag‐1, thereby strongly suggesting that calcineurin activation in vivo occurs during the late stages of neuronal migration, possibly during synaptogenesis with mossy fibres. We therefore propose that calcineurin might play an important role as a switch between transcriptional programs during neuronal development.
Sleep and wakefulness modulate gene expression in Drosophila
Authors: Cirelli Chiara , LaVaute Timothy M. , Tononi Giulio 
Published: December 2005

AbstractIn the mammalian brain, sleep and wakefulness are associated with widespread changes in gene expression. Sleep in fruit flies shares many features with mammalian sleep, but it is currently unknown to what extent behavioral states affect gene expression in Drosophila. To find out, we performed a comprehensive microarray analysis of gene expression in spontaneously awake, sleep‐deprived and sleeping flies. Fly heads were collected at 4 am, after 8 h of spontaneous sleep or sleep deprivation, and at 4 pm, after 8 h of spontaneous wakefulness. As in rats, we found that behavioral state and time of day affect Drosophila gene expression to a comparable extent. As in rats, transcripts with higher expression in wakefulness and in sleep belong to different functional categories, and in several cases these groups overlap with those previously identified in rats. Wakefulness‐related genes code for transcription factors and for proteins involved in the stress response, immune response, glutamatergic transmission, and carbohydrate metabolism. Sleep‐related transcripts include the glial gene anachronism and several genes involved in lipid metabolism. Finally, the expression of many wakefulness‐related and sleep‐related Drosophila transcripts is also modulated by the time of day, suggesting an interaction at the molecular level between circadian and homeostatic mechanism of sleep regulation.
Hypoxia‐activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen‐sensitive cells
Authors: Zakrzewska Adriana , Schnell Phillip O. , Striet Justin B. , Hui Anna , Robbins Jennifer R. , Petrovic Milan , Conforti Laura , Gozal David , Wathelet Marc G. , Czyzyk‐Krzeska Maria F. 
Published: December 2005

AbstractTranscription co‐activators and histone acetyltransferases, p300 and cyclic AMP responsive element‐binding protein‐binding protein (CBP), participate in hypoxic activation of hypoxia‐inducible genes. Here, we show that exposure of PC12 and cells to 1–10% oxygen results in hyperphosphorylation of p300/CBP. This response is fast, long lasting and specific for hypoxia, but not for hypoxia‐mimicking agents such as desferioxamine or Co2+ ions. It is also cell‐type specific and occurs in pheochromocytoma PC12 cells and the carotid body of rats but not in hepatoblastoma cells. The p300 hyperphosphorylation specifically depends on the release of intracellular calcium from inositol 1,4,5‐triphosphate (IP3)‐sensitive stores. However, it is not inhibited by pharmacological inhibitors of any of the kinases traditionally known to be directly or indirectly calcium regulated. On the other hand, p300 hyperphosphorylation is inhibited by several different inhibitors of the glucose metabolic pathway from generation of NADH by glyceraldehyde 3‐phosphate dehydrogenase, through the transfer of NADH through the glycerol phosphate shuttle to ubiquinone and complex III of the mitochondrial respiratory chain. Inhibition of IP3‐sensitive calcium stores decreases generation of ATP, and this inhibition is significantly stronger in hypoxia than in normoxia. We propose that the NADH glycerol phosphate shuttle participates in generating a pool of ATP that serves either as a co‐factor or a modulator of the kinases involved in the phosphorylation of p300/CBP during hypoxia.
Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine‐induced antinociception
Authors: Narita Minoru , Suzuki Masami , Narita Michiko , Niikura Keiichi , Nakamura Atsushi , Miyatake Mayumi , Aoki Takeshi , Yajima Yoshinori , Suzuki Tsutomu 
Published: December 2005

AbstractIt is well known that prolonged exposure to morphine results in tolerance to morphine‐induced antinociception. In the present study, we found that either intrathecal (i.t.) or subcutaneous (s.c.) injection of the selective metabotropic glutamate receptor 5 (mGluR5) antagonist, methyl‐6‐(phenylethynyl)‐pyridine hydrochloride (MPEP), attenuated the development of tolerance to morphine‐induced antinociception. Using the receptor binding assay, we found here that the number of mGluR5 in the mouse spinal cord was significantly increased by repeated treatment with morphine. Furthermore, repeated treatment with morphine produced a significant increase in the level of mGluR5 immunoreactivity in the dorsal horn of the mouse spinal cord. Double‐labeling experiments showed that the increased mGluR5 was predominantly expressed in the neurons and sparsely expressed in the processes of astrocytes following repeated treatment with morphine. Consistent with these results, the response of Ca2+to the selective group I mGluR agonist, 3,5‐dihydroxyphenylglycine (DHPG), in cultured spinal cord neurons was potently enhanced by 3 days ofin vitrotreatment with morphine. These findings support the idea that the increased mGluR5 following repeated treatment with morphine leads to enhanced neuronal excitability and synaptic transmission in the dorsal horn of the spinal cord and, in turn, suppresses the morphine‐induced antinociception in mice.
α‐Tocopheryl succinate selectively induces apoptosis in neuroblastoma cells: potential therapy of malignancies of the nervous system?
Authors: Swettenham Emma , Witting Paul K. , Salvatore Brian A. , Neuzil Jiri 
Published: December 2005

AbstractVitamin E (VE) analogues, epitomized by α‐tocopheryl succinate (α‐TOS), are potent inducers of apoptosis and anti‐cancer agents. Here, we tested their effect on the highly malignant N‐type neuroblastoma (Nb) cells and their differentiated, neurone‐like counterparts. Nb cells were highly susceptible to several VE analogues, while differentiated Nb cells were relatively resistant to α‐TOS. The importance of caspase‐9 rather than caspase‐8, as judged by specific siRNAs studies, together with the loss of the inner mitochondrial potential, suggests that α‐TOS triggers apoptosis in Nb cells via the mitochondrial pathway. Cultured Nb cells were sensitized to α‐TOS by pre‐treatment with Bcl‐2, Bcl‐xL or Mcl‐1 siRNAs, while the malignant cell line was more resistant to the vitamin E analogue when Bax was knocked down. In contrast, overexpression of Bcl‐2 in Nb cells rendered them more resistant to α‐TOS‐induced apoptosis. The resistance of differentiated Nb cells to α‐TOS‐mediated apoptosis occurred via two modes: first, by up‐regulation of the anti‐apoptotic Bcl‐2 family proteins and second, by accumulation of decreased levels of reactive oxygen species when challenged with α‐TOS. We conclude that α‐TOS is highly selective in killing malignant brain cancer cells while relatively inert toward differentiated neuronal cells, and that vitamin E analogues may be novel therapeutics for the treatment of tumours such as neuroblastomas.
Evidence that protein kinase Cα interacts with and regulates the glial glutamate transporter GLT‐1
Authors: I. González Marco , Susarla Bala T. S. , Robinson Michael B. 
Published: December 2005

AbstractMany of the sodium‐dependent neurotransmitter transporters are rapidly (within minutes) regulated by protein kinase C (PKC), with changes in activity being correlated with changes in transporter trafficking to or from the plasma membrane. Our recent studies suggest that one of the classical subtypes of PKC, PKCα, may selectively mediate redistribution of the neuronal glutamate transporter, excitatory amino acid carrier (EAAC)1, and show that PKCα can be co‐immunoprecipitated with EAAC1. When the glial glutamate transporter GLT‐1a is transfected into C6 glioma cells, this transporter is internalized in response to activation of PKC, but the PKC subtype involved in this regulation is unknown. In the present study, expression of the phorbol ester‐activated subtypes of PKC was examined in C6 glioma transfected with GLT‐1. Of the classical subtypes, only PKCα was detected, and of the non‐classical subtypes, PKCδ and PKCε were detected. In this system, phorbol ester‐dependent internalization of GLT‐1 was blocked by a general inhibitor of PKCs (bisindolylmaleimide II) and by concentrations of Gö6976 that selectively block classical PKCs, but not by an inhibitor of PKCδ (rottlerin). PKCα immunoreactivity was found in GLT‐1 immunoprecipitates obtained from transfected C6 cells and from crude rat brain synaptosomes, a milieu that better mimicsin vivoconditions. The amount of PKCα in both types of immunoprecipitate was modestly increased by phorbol ester, and this increase was blocked by a PKC antagonist. These studies suggest that PKCα may be required for the regulated redistribution of GLT‐1.