bluuebunny/crossref_metadata_2025 huggingface dataset:
Ideology, Party Factionalism and Policy Change: An integrated dynamic theory
Authors: Budge Ian , Ezrow Lawrence , McDonald Michael D.
Published: July 2010

Operationalized as a simulation and checked against 1,737 policy shifts in twenty-four post-war democracies, this theory of party position-taking offers both an explanation and specific postdictions of party behaviour, synthesizing some previous approaches and linking up with mandate theories of political representation. These wider implications are considered at the beginning and the end of the article.
Electoral System Change, Generations, Competitiveness and Turnout in New Zealand, 1963–2005
Authors: Vowles Jack
Published: July 2010

In 1996, New Zealand changed its electoral system from single-member plurality (SMP) to a Mixed Member Proportional (MMP) system. This article addresses the effects on turnout of electoral system change, generational differences and national and district-level competitiveness. Both theory and cross-sectional empirical evidence indicate that turnout should be higher after the change to MMP. Yet turnout has declined. Most of this turns out to be an effect of lag effects generated by longer-term trends of declining competition, and generational experiences. MMP has shifted the main focus of electoral competition from the district to the national level, with consequent changes in turnout distribution. Electoral boundary changes also have negative effects under MMP, and most MMP elections have taken place after an electoral redistribution.
Short‐latency somatosensory evoked potentials in infantile autism: evidence of hyperactivity in the right primary somatosensory area
Authors: Miyazaki Masahito , Fujii Emiko , Saijo Takahiko , Mori Kenji , Hashimoto Toshiaki , Kagami Shoji , Kuroda Yasuhiro
Published: July 2010

Children with infantile autism sometimes show hyperesthesia or hypoesthesia to touch, pain, and/or temperature. To clarify the pathophysiology, we examined short‐latency somatosensory evoked potentials (S‐SEPs), elicited by median nerve stimulation, in 24 children with infantile autism (17 males, seven females; age range 2y 2mo–9y; mean age 4y 2mo [SD 1y 7mo]). We also evaluated relationships between S‐SEP findings and clinical manifestations. Of the 24 children, 10 showed abnormal S‐SEPs as follows: prolonged peak latency of N20 (n=2), extended interpeak latency of P13/14–N20 (n=7), appearance of a giant SEP (n=1), and a more than twofold right hemispheric peak‐to‐peak amplitude predominance of N20–P25 (n=5). In addition, a peak‐to‐peak amplitude of N20–P25 elicited by left median nerve stimuli was significantly higher than that obtained with right median nerve stimuli, which indicated right hemispheric hyperactivity relative to the left (p=0.008). Infantile autism is frequently associated with somatosensory abnormalities and right hemispheric hyperactivity relative to the left, especially in the primary somatosensory area. This is believed to contribute to the pathophysiology of infantile autism, especially the idiopathic form.
Psychometric properties of the quality of life questionnaire for children with CP
Authors: Waters Elizabeth , Davis Elise , Mackinnon Andrew , Boyd Roslyn , Graham H Kerr , Kai Lo Sing , Wolfe Rory , Stevenson Richard , Bjornson Kristie , Blair Eve , Hoare Peter , Ravens‐Sieberer Ulrike , Reddihough Dinah
Published: July 2010

This paper describes the development and psychometric properties of a condition‐specific quality of life instrument for children with cerebral palsy (CP QOL‐Child). A sample of 205 primary caregivers of children with CP aged 4 to 12 years (mean 8y 5mo) and 53 children aged 9 to 12 years completed the CP QOL‐Child. The children (112 males, 93 females) were sampled across Gross Motor Function Classification System (GMFCS) levels (Level I=18%, II=28%, III=14%, IV=11%, V=27%). Primary caregivers also completed other measures of child health (Child Health Questionnaire; CHQ), QOL (KIDSCREEN), and functioning (GMFCS). Internal consistency ranged from 0.74 to 0.92 for primary caregivers and from 0.80 to 0.90 for child self‐report. For primary caregivers, 2‐week test‐retest reliability ranged from 0.76 to 0.89. The validity of the CP QOL is supported by the pattern of correlations between CP QOL‐Child scales with the CHQ, KIDSCREEN, and GMFCS. Preliminary statistics suggest that the child self‐report questionnaire has acceptable psychometric properties. The questionnaire can be freely accessed at http://www.deakin.edu.ac/hmnbs/chase/cerebralpalsy/cp_qol_home.php
A previously undescribed leukodystrophy in Leigh syndrome associated with T9176C mutation of the mitochondrial ATPase 6 gene
Authors: Hung Po‐Cheng , Wang Huei‐Shyong
Published: July 2010

We report two male Taiwanese siblings in whom the T→C point mutation at nucleotide 9176 of the mitochondrial ATPase 6 gene (m.9176T>C mutation) was associated with early onset hypotonia, lactic acidosis, and death due to respiratory arrest at 7 and 10 months old. Brain MRI showed lesions over diffuse white matter and the bilateral posterior limbs of the internal capsule. The m.9176T>C mutation is suggested as the cause of the bilateral striatal necrosis and Leigh syndrome. However, leukodystrophy in Leigh syndrome associated with m.9176T>C mutation has never been reported before. We suggest that m.9176T>C mutation could be a new aetiology for leukodystrophy in children with Leigh syndrome.
Radial basis function regression methods for predicting quantitative traits using SNP markers
Authors: LONG NANYE , GIANOLA DANIEL , ROSA GUILHERME J. M. , WEIGEL KENT A. , KRANIS ANDREAS , GONZÁLEZ-RECIO OSCAR
Published: July 2010

A challenge when predicting total genetic values for complex quantitative traits is that an unknown number of quantitative trait loci may affect phenotypes via cryptic interactions. If markers are available, assuming that their effects on phenotypes are additive may lead to poor predictive ability. Non-parametric radial basis function (RBF) regression, which does not assume a particular form of the genotype–phenotype relationship, was investigated here by simulation and analysis of body weight and food conversion rate data in broilers. The simulation included a toy example in which an arbitrary non-linear genotype–phenotype relationship was assumed, and five different scenarios representing different broad sense heritability levels (0·1, 0·25, 0·5, 0·75 and 0·9) were created. In addition, a whole genome simulation was carried out, in which three different gene action modes (pure additive, additive+dominance and pure epistasis) were considered. In all analyses, a training set was used to fit the model and a testing set was used to evaluate predictive performance. The latter was measured by correlation and predictive mean-squared error (PMSE) on the testing data. For comparison, a linear additive model known as Bayes A was used as benchmark. Two RBF models with single nucleotide polymorphism (SNP)-specific (RBF I) and common (RBF II) weights were examined. Results indicated that, in the presence of complex genotype–phenotype relationships (i.e. non-linearity and non-additivity), RBF outperformed Bayes A in predicting total genetic values using SNP markers. Extension of Bayes A to include all additive, dominance and epistatic effects could improve its prediction accuracy. RBF I was generally better than RBF II, and was able to identify relevant SNPs in the toy example.
Bayesian mixture structural equation modelling in multiple-trait QTL mapping
Authors: MI XIAOJUAN , ESKRIDGE KENT , WANG DONG , BAENZIGER P. STEPHEN , CAMPBELL B. TODD , GILL KULVINDER S. , DWEIKAT ISMAIL
Published: July 2010

Quantitative trait loci (QTLs) mapping often results in data on a number of traits that have well-established causal relationships. Many multi-trait QTL mapping methods that account for correlation among the multiple traits have been developed to improve the statistical power and the precision of QTL parameter estimation. However, none of these methods are capable of incorporating the causal structure among the traits. Consequently, genetic functions of the QTL may not be fully understood. In this paper, we developed a Bayesian multiple QTL mapping method for causally related traits using a mixture structural equation model (SEM), which allows researchers to decompose QTL effects into direct, indirect and total effects. Parameters are estimated based on their marginal posterior distribution. The posterior distributions of parameters are estimated using Markov Chain Monte Carlo methods such as the Gibbs sampler and the Metropolis–Hasting algorithm. The number of QTLs affecting traits is determined by the Bayes factor. The performance of the proposed method is evaluated by simulation study and applied to data from a wheat experiment. Compared with single trait Bayesian analysis, our proposed method not only improved the statistical power of QTL detection, accuracy and precision of parameter estimates but also provided important insight into how genes regulate traits directly and indirectly by fitting a more biologically sensible model.
L2-Boosting algorithm applied to high-dimensional problems in genomic selection
Authors: GONZÁLEZ-RECIO OSCAR , WEIGEL KENT A. , GIANOLA DANIEL , NAYA HUGO , ROSA GUILHERME J. M.
Published: July 2010

TheL2-Boosting algorithm is one of the most promising machine-learning techniques that has appeared in recent decades. It may be applied to high-dimensional problems such as whole-genome studies, and it is relatively simple from a computational point of view. In this study, we used this algorithm in a genomic selection context to make predictions of yet to be observed outcomes. Two data sets were used: (1) productive lifetime predicted transmitting abilities from 4702 Holstein sires genotyped for 32 611 single nucleotide polymorphisms (SNPs) derived from the Illumina® BovineSNP50 BeadChip, and (2) progeny averages of food conversion rate, pre-corrected by environmental and mate effects, in 394 broilers genotyped for 3481 SNPs. Each of these data sets was split into training and testing sets, the latter comprising dairy or broiler sires whose ancestors were in the training set. Two weak learners, ordinary least squares (OLS) and non-parametric (NP) regression were used for theL2-Boosting algorithm, to provide a stringent evaluation of the procedure. This algorithm was compared with BL [Bayesian LASSO (least absolute shrinkage and selection operator)] and BayesA regression. Learning tasks were carried out in the training set, whereas validation of the models was performed in the testing set. Pearson correlations between predicted and observed responses in the dairy cattle (broiler) data set were 0·65 (0·33), 0·53 (0·37), 0·66 (0·26) and 0·63 (0·27) for OLS-Boosting, NP-Boosting, BL and BayesA, respectively. The smallest bias and mean-squared errors (MSEs) were obtained with OLS-Boosting in both the dairy cattle (0·08 and 1·08, respectively) and broiler (−0·011 and 0·006) data sets, respectively. In the dairy cattle data set, the BL was more accurate (bias=0·10 and MSE=1·10) than BayesA (bias=1·26 and MSE=2·81), whereas no differences between these two methods were found in the broiler data set.L2-Boosting with a suitable learner was found to be a competitive alternative for genomic selection applications, providing high accuracy and low bias in genomic-assisted evaluations with a relatively short computational time.
The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives
Authors: Lelli-Chiesa G. , Kempton M. J. , Jogia J. , Tatarelli R. , Girardi P. , Powell J. , Collier D. A. , Frangou S.
Published: July 2010

Background

The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how theCOMTVal158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.

Method

We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.

Results

Irrespective of clinical phenotype, the Val158allele was associated with greater amygdala activation and the Met158allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.

Conclusions

Our results suggest that theCOMTVal158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.
Far infrared pedestrian detection and tracking for night driving
Authors: Olmeda Daniel , de la Escalera Arturo , Armingol José María
Published: July 2010

This paper presents a module for pedestrian detection from a moving vehicle in low-light conditions. The algorithm make use of a single far infrared camera based on a microbolometer. Images of the area ahead of the vehicle are analyzed to determine if any pedestrian might be in its trajectory. Detection is achieved by searching for distributions of temperatures in the scene similar to that of the human body. Those areas with an appropriate temperature, size, and position in the image are classified, by means of a correlation between them and some probabilistic models, which represents the average temperature of the different parts of the human body. Finally, those pedestrians found are tracked in a subsequent step, using an unscented Kalman filter. This final stage of the algorithm enables the algorithm to predict the trajectory of the pedestrian, in a way that does not depend on the movement of the camera. The aim of this system is to warn the vehicle's driver and reduce the reaction time in case an emergency break is necessary.
The case of the undying debt
Authors: Velde François R.
Published: July 2010

The French government currently honors a very unusual debt contract: an annuity that was issued in 1738 and currently yields €1.20 per year, payable to the descendants of its original recipient. I tell the story of this unique debt, which serves as an anecdotal but symbolic summary of French public finances since the eighteenth century. Created by a powerful nobleman for one of his servants, it survived the turmoil of the French Revolution, became part of the public debt and has been scrupulously honored to this day, even though its value has been eroded away by decades of inflation.
L2 effects on L1 event conceptualization
Authors: BYLUND EMANUEL , JARVIS SCOTT
Published: July 2010

The finding that speakers of aspect languages encode event endpoints to a lesser extent than do speakers of non-aspect languages has led to the hypothesis that there is a relationship between grammatical aspect and event conceptualization (e.g., von Stutterheim and Nüse, 2003). The present study concerns L1 event conceptualization in 40 L1 Spanish – L2 Swedish bilinguals (all near-native speakers of Swedish). Spanish and Swedish differ as regards grammatical aspect: whereas Swedish lacks this grammatical category, Spanish conveys aspect through verbal morphology and periphrasis. The principal aim of the study was to explore the relationship between productive event conceptualization patterns and receptive decoding proficiency related to aspectual contrasts. The participants were asked to provide oral L1 Spanish descriptions of video clips projecting motion events with different degrees of endpoint orientation (see von Stutterheim, 2003). In addition, they took a grammaticality judgment test concerning verb and gender agreement, verbal clitics and aspectual contrasts. Compared with baseline data from monolingual Spanish speakers, the results on endpoint encoding show that the bilinguals mention the endpoints of motion events to a higher degree than the Spanish control group does. Moreover, it was shown that the weaker the bilinguals' discrimination of aspectual errors on the grammaticality judgment test, the more prone they were to encoding endpoints. This result consequently furthers the hypothesis about the interconnectedness between grammatical aspect and event conceptualization. The results were further interpreted as indicating that the bilinguals are influenced by the Swedish-like tendency to attend to the boundedness rather than the ongoingness of events.
Connecting near‐field and far‐field earthquake triggering to dynamic strain
Authors: van der Elst Nicholas J. , Brodsky Emily E.
Published: July 2010

Any earthquake can trigger more earthquakes. This triggering occurs in both the classical aftershock zone as well as the far field. These populations of triggered earthquakes may or may not be distinct in terms of triggering mechanism. Here we look for a distinction between the populations by examining how the observed intensity of triggering scales with the amplitude of the triggering strain in each. To do so, we apply a new statistical metric based on earthquake interevent times to a large data set and measure earthquake triggering as a function of dynamic strain amplitude, where strain is estimated from empirical ground motion regressions. This method allows us to identify triggering at dynamic strain amplitudes down to 3 × 10−9, orders of magnitude smaller than previously reported. This threshold appears to be an observational limit and shows that extremely small dynamic strains can trigger faults that are sufficiently near failure. Using a probabilistic model to transform measured interevent times to seismicity rate changes, we find that triggering rates in the far field scale with peak dynamic strain. This scaling, projected into the near field, accounts for 15%–60% of earthquakes within 6 km of magnitude 3–5.5 earthquakes. Statistical seismicity simulations validate the interevent time method and show that the data are consistent with the number of far‐field triggered earthquakes being linearly proportional to peak dynamic strain. We interpret the additional near‐field component as reflecting either static stress triggering, more effective dynamic triggering at higher frequencies, or a concentration of aftershock nucleation sites very near main shocks.
Impact of heterogeneous ice nuclei on homogeneous freezing events in cirrus clouds
Authors: Spichtinger P. , Cziczo D. J.
Published: July 2010

The influence of initial heterogeneous nucleation on subsequent homogeneous nucleation events in cirrus clouds is investigated using a box model which includes the explicit impact of aerosols on the nucleation of ice crystals and a new sedimentation scheme. Different effects are discussed, namely the impact of external versus internal mixtures of heterogeneous ice nuclei and the influence of size‐dependent freezing thresholds. Several idealized experiments are carried out, which show that the treatment of external mixtures of ice nuclei can strongly change subsequent homogeneous nucleation events (i.e., the ice crystal number densities) over a large variety of environmental conditions relevant for the upper troposphere. In most cases a strong reduction in ice crystal number concentrations formed in subsequent homogeneous freezing events is observed. The use of size‐dependent freezing thresholds can change cloud properties when compared to more simple parameterizations and is most important at largest ice nuclei concentrations.
Influence of tropical convection on the Southern Hemisphere ozone maximum during the winter to spring transition
Authors: Hitchman M. H. , Rogal M. J.
Published: July 2010

During the Southern Hemisphere (SH) winter a zonally asymmetric maximum in column ozone develops south of Australia, which amplifies from August through October. This ozone maximum lies in the band 50–60°S and extends from the southern Indian Ocean to the eastern Pacific. It is proposed that the location of the ozone maximum is due to the geographical distribution of outflow from tropical convection in the upper troposphere and lower stratosphere (UTLS), which is concentrated over the southern Indian Ocean. This southward flow of tropical air creates subtropical anticyclones in the UTLS and provides the angular momentum for the entrance to the Australian westerly jet. The ozone‐rich troughs in synoptic waves breaking on the jet contribute to the monthly mean ozone maximum poleward of the jet. As Indonesian convection contracts zonally and shifts eastward during SH spring, so do the Australian jet and ozone maximum. In addition, extratropical planetary waves become more active from August through October. Convective outflow surges lead to amplification of subtropical anticyclones, which often extend into the lower stratosphere and merge with stalling planetary wave ridges. Amplification of these ozone‐rich ridges over the high‐latitude South Pacific contributes to the eastward shift of the ozone maximum. The UTLS over the southern Indian Ocean appears to be a sensitive region where tropical convection can influence extratropical planetary waves via excitation of subtropical anticyclones and propagation of Rossby wave activity through the connecting westerly waveguide.
Direct climate effect of black carbon in China and its impact on dust storms
Authors: Gu Yu , Liou K. N. , Chen Wen , Liao Hong
Published: July 2010

Dust storms originating in the Gobi desert and the surrounding areas critically impact weather, climate, and public health in China and neighboring Pacific Rim countries. In the decades between 1954 and 2007, reports of annual dust storm occurrences and the corresponding amount of total precipitation at 753 Chinese meteorological sites show a reduction in the occurrence and intensity of dust storms and clearly demonstrate an inverse relationship between the two. The correlation between dust storm occurrence and temperature in northwestern China also displays a negative trend but is less significant. Using a global climate model, we demonstrate that increased loading of light‐absorbing aerosols in China, particularly black carbon (BC), is the primary reason for precipitation and temperature increases over northwestern China, and the consequence of reductions in dust storm frequency and intensity. The model‐simulated precipitation and temperature changes over northwestern China compare reasonably well with observed trends when a certain portion of BC has been added to the model, which significantly affects regional climate patterns through the heating of the air column. In addition to a reduction in dust storm intensity/frequency in response to an increase in BC, the model has also reproduced the substantial variability in precipitation which has been observed in other regions of China.
Tidal flow over three‐dimensional topography generates out‐of‐forcing‐plane harmonics
Authors: King Benjamin , Zhang H. P. , Swinney Harry L.
Published: July 2010

We conduct laboratory experiments and direct numerical simulations on internal gravity waves generated by tidal flow over a model three‐dimensional Gaussian mountain on the sea floor. When 2ω < N (where ω is the tidal frequency and N is the buoyancy frequency), the flow generates second harmonic internal waves that propagate perpendicular to the tidal forcing direction. These unexpected harmonics are observed only when the maximum slope of the bottom topography is greater than the slope of internal wave propagation. The out‐of‐plane harmonics saturate at a higher tidal forcing amplitude than the normal in‐tidal‐forcing‐plane harmonics, and could lead to increased wave breaking and mixing near rough topography in the ocean.
A Novel Inhibitory Role for Glucocorticoids in the Secretion of Angiotensinogen by C6 Glioma Cells
Authors: Sernia Conrad , Thomas Walter G.
Published: July 2010

Abstract: Astrocytes have been identified as the primary source of brain angiotensinogen (Ao), but the regulation of the secretion of this protein from astrocytes is poorly defined. In this study, the rat C6 glioma cell line was used as an astrocyte model to investigate the regulation of Ao secretion. C6 cultures secreted Ao at a rate of 4.05 ± 1.52 (mean ± SD) ng of Ao/106 cells/24 h as determined by a direct radioimmunoassay. This rate was not significantly altered by the hormones thyroxine, estradiol, angiotensin II, growth hormone, and prostaglandins or by increased levels of intracellular cyclic AMP. Treatment with the synthetic glucocorticoid dexamethasone (DEX; 10–6M) reduced the rate of Ao secretion to 1.82 ± 0.28 ng of Ao/108 cells/24 h. By comparison, the basal secretion rate for rat H4 hepatoma cells was 142.4 ± 10.0 ng of Ao/106 cells/24 h, and this increased fourfold (572.4 ± 173.1 ng/106 cells/ 24 h) in the presence of 10–6M DEX. Both these inhibitory (C6) and stimulatory (H4) actions of DEX were dose related. The inhibition observed in C6 cells was mimicked by RU28362, a pure glucocorticoid agonist, and reversed by the antagonist RU486, demonstrating that DEX was functioning as a true glucocorticoid. The action of DEX was also antagonized by the cyclic AMP analogue N6,2′‐O‐ dibutyryladenosine 3′:5′‐cyclic monophosphate (dBcAMP) (control, DEX, and DEX + dBcAMP, 3.58 ± 0.73, 1.69 ± 0.82, and 4.93 ± 1.88 ng of Ao/106 cells/24 h, respectively, and by the β‐adrenergic agonist isoprenaline, which stimulates cyclic AMP production. It was concluded that glucocorticoids inhibit Ao secretion, possibly by interacting with a cyclic AMP‐responsive pathway. The inhibition of Ao production by DEX is a novel observation supporting the view that regulation of Ao is tissue specific.
Cholinergic Deafferentation of Dorsal Hippocampus by Fimbria‐Fornix Lesioning Differentially Regulates Subtypes (m1‐m5) of Muscarinic Receptors
Authors: Wall Stephen J. , Wolfe Barry B. , Kromer Lawrence F.
Published: July 2010

Abstract:Unilateral aspiration lesions of the rostral supracallosal stria/cingulum bundle and fimbria‐fornix were performed on adult female rats. Ten and 24 days post lesioning, an elevation (17%; p<0.01) of total muscarinic receptors was observed in lesioned versus control hippocampi. By using antisera selective for each of the five molecularly defined subtypes (m1‐m5) of muscarinic receptors, significant changes were observed in the levels of expression for at least four receptor proteins. Three receptor subtypes increased in density: m1 by 14% (from 943 to 1,078 fmol/mg); m3 by 77% (from 150 to 268 fmol/ mg); and m4 by 29% (from 220 to 285 fmol/mg). In contrast, a 22% decrease in the density of m2 receptors was found (from 220 to 173 fmol/mg). Detectable levels of m5 receptors were low in the hippocampus (∼1% of total receptors), and reliable measurements were not obtained. The directions of these changes are likely to be related to the pre‐ or postsynaptic localization of these receptor subtypes.
Tyrosine Phosphorylation and Activation of Mitogen‐ Activated Protein Kinase in the Rat Brain Following Transient Cerebral Ischemia
Authors: Hu Bing‐Ren , Wieloch Tadeusz
Published: July 2010

Abstract: Activation of trophic factor receptors stimulates tyrosine phosphorylation on proteins and supports neuronal survival. We report that in the recovery phase following reversible cerebral ischemia, tyrosine phosphorylation increases in the membrane fraction of the resistant hippocampal CA3/dentate gyrus (DG) region, whereas in the sensitive CA1 region or striatum, tyrosine phosphorylation is less marked or decreases. In the cytosolic fractions, a 42‐kDa protein, identified as mitogen‐activated protein (MAP) kinase, is markedly phosphorylated and activated immediately following ischemia, in particular in CA3/DG, but not in striatum. In the CA1 region, phosphorylation of MAP kinase is less intense and decreases later during re‐ perfusion, which could explain the delay of neuronal degeneration in this structure. The data suggest that in ischemia‐resistant neurons the growth factor receptor‐coupled signaling cascade is stimulated and, through its effects on DNA transcription and mRNA translation, supports neuronal survival.
Binding of Cholecystokinin‐8 (CCK‐8) Peptide Derivatives to CCKAand CCKBReceptors
Authors: Schäfer Ute , Harhammer Rainer , Boomgaarden Monika , Sohr Reinhard , Ott Tilmann , Henklein Peter , Repke Heinrich
Published: July 2010

Abstract: The structural requirements for the selective binding of cholecystokinin‐8 (CCK‐8)‐related peptides to peripheral (CCKA) receptors are not sufficiently understood. In this study, the interaction of a series of newly shortened analogues of CCK‐8 with both receptor subtypes was analyzed by displacement studies using [3H]‐CCK‐8 and125l‐Bolton‐Hunter (BH)‐CCK‐8 as radioligands. The pentapeptide derivative of CCK‐8, succinyl‐Tyr (SO3H)‐Met‐Gly‐Trp‐Met‐phenethylamide, was found to bind selectively with high affinity to the CCKAreceptor. The replacement of Met28and/or Met31by norleucine and of L‐Trp30by its D‐analogue had no significant effect on the binding properties of the peptide. Further C‐terminal shortening resulted in a drastic loss of affinity and selectivity of the CCK receptor binding.
Stereoselectivity of the Inhibition of [3H]Hemicholinium‐3 Binding to the Sodium‐Dependent High‐Affinity Choline Transporter by the Enantiomers of a‐ and β‐Methylcholine
Authors: Ferguson S. S. G. , Collier B.
Published: July 2010

Abstract: In a previous report, we showed that the enantiomers of α‐ and β‐methylcholine inhibited choline uptake with Stereoselectivity, but that their transport by the choline carrier of nerve terminals showed stereospecificity. The present experiments used the same choline analogues to determine if either of the above characteristics pertains to their ability to interact with the [3H]‐hemicholinium‐3 binding site present on striatal membranes and synaptosomes. [3H]Hemicholinium‐3 binding to striatal membranes could be inhibited stereoselectively by the enantiomers of β‐methylcholine, butR(+)‐α‐methyl‐choline was little better than its enantiomer in this test. However, [3H]hemicholinium‐3 binding to striatal synaptosomes was inhibited stereoselectively by the enantiomers of both α‐ and β‐methylcholine. This difference between the properties of [3H]hemicholinium‐3 binding to membranes or to synaptosomes appears related to the presence of two ligand binding states. The [3H]hemicholinium‐3 binding site could be shifted to a low‐affinity state by ATP treatment and to a high‐affinity state by EDTA washing. When the [3H]hemicholinium‐3 binding site existed in its low‐affinity state, binding was inhibited stereoselectively by the enantiomers of both a‐ and β‐methylcholine, but when shifted to its high‐affinity state, it was inhibited stereoselectively only by the enantiomers of β–methylcholine. We conclude that hemicholinium‐3 interacts with the substrate recognition site of the high‐affinity choline transporter, but that the Stereoselectivity of this site changes depending on its affinity state.
Metabolic and Biosynthetic Alterations in Cultured Astrocytes Exposed to Hypoxia/Reoxygenation
Authors: Hori Osamu , Matsumoto Masayasu , Maeda Yusuke , Ueda Hirokazu , Ohtsuki Toshiho , Stern David M. , Kinoshita Taroh , Ogawa Satoshi , Kamada Takenobu
Published: July 2010

To investigate the astrocyte response to hypoxia/reoxygenation, as a model relevant to the pathogenesis of ischemic injury, cultured rat astrocytes were exposed to hypoxia. On restoration of astrocytes to normoxia, there was a dramatic increase in protein synthesis within 3 h, and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis of metabolically labeled astrocyte lysates showed multiple induced bands on fluorograms. Levels of cellular ATP declined during the first 3 h of reoxygenation and the concentration of AMP increased to ± 3.6 nmol/mg of protein within 1 h of reoxygenation. Reoxygenated astrocytes generated oxygen free radicals early after replacement into ambient air, and addition of diphenyliodonium, an NADPH oxidase inhibitor, diminished the generation of free radicals as well as the induction of several bands on fluorogram. Although addition of cycloheximide on reoxygenation resulted in inhibition of both astrocyte protein synthesis and accumulation of cellular AMP, it caused cell death within 6 h, suggesting the importance of protein synthesis in adaptation of hypoxic astrocytes to reoxygenation. Potential physiologic significance of biosynthetic products of astrocytes in hypoxia/reoxygenation was suggested by the recovery of glutamate uptake. These results indicate that the astrocyte response to hypoxia/reoxygenation includes generation of oxygen free radicals and de novo synthesis of products that influence cell viability and function in ischemia.
In Vitro Activation of Rat Brain Protein Kinase C by Polyenoic Very‐Long‐Chain Fatty Acids
Authors: Hardy Stephen J. , Ferrante Antonio , Robinson Brenton S. , Johnson David W. , Poulos Alf , Clark Katherine J. , Murray Andrew W.
Published: July 2010

Abstract: A variety of fatty acids including the cis‐polyunsaturated very‐long‐chain fatty acids (VLCFA) (>22 carbon atoms) common in retina, spermatozoa, and brain were examined for their ability to activate protein kinase C (PKC) purified from rat brain. Arachidonic [20:4(n‐6)], eicosapentaenoic [20:5(n‐3)], and docosahexaenoic [22:6(n‐ 3)] acids as well as the VLCFA dotriacontatetraenoic [32:4(n‐6)] and tetratriacontahexaenoic [34:6(n‐3)] were equally capable of activating PKC in vitro with maximal activity being between 25 and 50 μM. The phorbol ester 12‐O‐tetradecanoylphorbol 13‐acetate further enhanced the in vitro activation of PKC when added to the protein kinase assay system with the fatty acids. The fully saturated arachidic acid (20:0) was inactive in both assay systems. The potential significance of the in vitro activation of PKC by the VLCFA is discussed.
Differential Activities of Protein Phosphatase Types 1 and 2A in Cytosolic and Participate Fractions from Rat Forebrain
Authors: Sim Alistair T. R. , Ratcliffe Elizabeth , Mumby Marc C. , Villa‐Moruzzi Emma , Rostas John A. P.
Published: July 2010

Abstract:The activities and concentrations of protein phosphates type 1 (PP1) and type 2A (PP2A) were compared in cytosol and particulate fractions of rat forebrain. Although the activity of PP2A was highest in the cytosol, immunoblot analysis with a PP2A‐specific antibody showed that there were significant levels of the enzyme in the particulate fraction. There was no significant difference between the concentration of PP2A in the cytosol and particulate fractions such that the low activity of PP2A in the particulate fraction represents an inactivation of this form of the enzyme. Similar analysis in skeletal muscle, heart, and liver showed this finding was unique to the brain. Similarly, the majority of PP1 activity was recovered in the cytosol, but most PP1 enzyme was associated with the particulate fraction. Comparison with other tissues showed that the activities of PP1 in the particulate fractions were similar but that the forebrain contained significantly more enzyme than the other tissues. Thus, like PP2A it appears that the specific activity of PP1 in the particulate fraction of rat forebrain is much lower than that of the cytosol and of the particulate fractions of other tissues. Elution of PP1 and PP2A from membranes with 0.5MNaCl plus 0.3% Triton X‐100 resulted in severalfold activation of both enzymes. That the majority of PP1 and PP2A in rat forebrain are associated with membrane structures but in a low activity state suggests that novel regulatory mechanisms exist that have considerable and unique potential for activation of protein dephosphorylation.
Expression of Preproenkephalin A Gene and Presence of Met‐Enkephalin in Dorsal Root Ganglia of the Adult Rat
Authors: Pohl M. , Collin E. , Bourgoin S. , Conrath M. , Benoliel J. J. , Nevo I. , Hamon M. , Giraud P. , Cesselin F.
Published: July 2010

Abstract: The expression of the preproenkephalin A gene was investigated in adult rat dorsal root ganglia (DRG). A radioimmunoassayable Met‐enkephalin (ME)‐like material was detected in 0.1 M HCl extracts of rat DRG, representing ∼60 pg of ME equivalents/mg of protein. Chromatographic analyses indicated that the major component of the ME‐like material coeluted with authentic ME. In northern blot experiments on total RNA extracted from DRG, a cDNA probe corresponding to the entire coding region of rat preproenkephalin A mRNA yielded a single band of the expected size for this mRNA, i.e., 1.5 kb. Polymerase chain reaction (PCR) experiments were carried out with DRG, striatum, and liver cDNAs using two primers flanking the 1,371–1,771 base region of the preproenkephalin A gene. Thirty PCR cycles performed on both striatum and DRG cDNAs generated a single band of 400 bp, as expected, whereas only trace amounts of this product were detectable using liver cDNAs. Nucleotide sequencing of the PCR product obtained with DRG cDNAs revealed a 100% homology with the 1,371–1,771 sequence of the preproenkephalin A gene. In situ hybridization with a cRNA probe showed that about 3.5% of DRG cells expressed the preproenkephalin A transcript. However, most of these cells probably did not process proenkephalin to enkephalins, as thorough immunohistochemical investigations with anti‐ME antibodies allowed the detection of only one in ∼6,000 cells (in 30 sections of DRG) that exhibited ME‐like immunoreactivity. Cells expressing preproenkephalin A mRNA were intermediate‐sized neurons, suggesting that primary afferent ME‐containing fibers belong to the A category and may participate in a local (spinal) inhibitory control of nociception.
Modulation of Adenylylcyclase by Protein Kinase C in Human Neurotumor SK‐N‐MC Cells: Evidence that the α Isozyme Mediates Both Potentiation and Desensitization
Authors: Zhou Xiao‐Ming , Curran Patricia , Baumgold Jesse , Fishman Peter H.
Published: July 2010

Abstract: Exposure of human SK‐N‐MC neurotumor cells to 4β‐phorbol 12‐myristate 13‐acetate (PMA) increased isoproterenol stimulation of cyclic AMP levels by severalfold. This potentiation was blocked by inhibitors of protein kinase C (PKC) and did not occur in cells in which PKC had been down‐regulated. PMA treatment also enhanced the stimulation by dopamine, cholera toxin, and forskolin. Thus, the effect of PMA on the adenylylcyclase system was postreceptor and involved either the guanine nucleotide binding regulatory (G) proteins or the cyclase itself. As PMA treatment did not impair the inhibition of isoproterenol stimulation by neuropeptide Y, an involvement of the inhibitory G protein Gi was unlikely. Cholate extracts of membranes from control and PMA‐treated cells were equally effective in the reconstitution of adenylylcyclase activity in S49 cyc− membranes, which lack the stimulatory G protein subunit Gsα; thus, Gs did not appear to be the target of PMA action. Membranes from PMA‐treated cells exhibited increased adenylylcyclase activity to all stimulators including Mn2+ and Mn2+ plus forskolin. In addition, activity was increased when control membranes were incubated with ATP and purified PKC from rat brain. This is consistent with a direct effect of PKC on the adenylylcyclase catalyst in SK‐N‐MC cells. PMA treatment also resulted in a shift to less sensitivity in the Kact for isoproterenol but not for dopamine or CGP‐12177 (a β3‐adrenergic agonist) stimulation. Thus, the β1 but not the D1 or β3 receptors were being desensitized by PKC activation. Analysis of SK‐N‐MC cells by western blotting with antibodies against different PKC isozymes revealed that both the α and ζ isozymes were present in these cells. Whereas PKC‐α was activated and translocated from cytosol to membrane by phorbol esters, the ζ isozyme was not. Thus, PKC‐α, which has been implicated in desensitization in other cell lines, also appears to potentiate adenylylcyclase activity.
Increased Intra‐ and Extracellular Concentrations of γ‐Glutamylglutamate and Related Dipeptides in the Ischemic Rat Striatum: Involvement of γ‐Glutamyl Transpeptidase
Authors: Orwar Owe , Li Xiaoying , Andiné Peter , Bergström Carl‐Magnus , Hagberg Henrik , Folestad Staffan , Sandberg Mats
Published: July 2010

Abstract: The present work relates to the possibility that the ATP‐independent enzyme γ‐glutamyl transpeptidase (EC 2.3.2.2), which has been postulated to be part of an amino acid uptake system, is active during cerebral ischemia. This was evaluated in the ischemic rat striatum by determination of intra‐ and extracellular concentrations of γ‐glutamyl dipeptides (the products of the transpeptidation) and glutathione (the physiological γ‐glutamyl donor). An ischemic period (0–30 and 31–60 min) resulted in prominent increases in the respective concentration of extracellular γ‐glutamylglutamate (24‐ and 67‐fold), γ‐glutamyltaurine + γ‐glutamylglycine (5.8‐ and 19‐fold), and γ‐glutamylglutamine (2.6‐ and 6.8‐fold) as revealed using in vivo microdialysis. The changes coincided with increased respective extracellular concentrations of glutamate (83‐ and 115‐fold), taurine (17‐ and 25‐fold), glycine (4.6‐ and 6.1‐fold), and glutamine (1.7‐ and 2.1‐fold). Furthermore, under anoxic conditions in vitro (0–30 and 0–60 min), respective striatal tissue concentrations were increased for γ‐glutamylglutamate (20‐ and 17‐fold), γ‐glutamyltaurine (6.7‐ and 11‐fold), γ‐glutamylglutamine (1.7‐ and 1.2‐fold), and γ‐glutamylglycine (14‐ and 18‐fold), whereas glutathione levels were, on an average, decreased by ∼350 µM. In summary, γ‐glutamyl transpeptidase is involved in de novo dipeptide synthesis in the mammalian brain during anoxic conditions, indicating transport of amino acids such as glutamate.
Alterations in Regional Brain Catecholamine Concentrations After Experimental Brain Injury in the Rat
Authors: McIntosh Tracy K. , Yu Thomas , Gennarelli Thomas A.
Published: July 2010

Abstract: Although activation of brain catecholaminergic systems has been implicated in the cerebrovascular and metabolic changes during subarachnoid hemorrhage, cerebral ischemia, cortical ablation, and cortical freeze lesions, little is known of the response of regional brain catecholamine systems to traumatic brain injury. The present study was designed to characterize the temporal changes in concentrations of norepinephrine (NE), dopamine (DA), and epinephrine (E) in discrete brain regions following experimental fluid‐percussion traumatic brain injury in rats. Anesthetized rats were subjected to fluid‐percussion brain injury of moderate severity (2.2–2.3 atm) and killed at 1 h, 6 h, 24 h, 1 week, and 2 weeks postinjury (n = 6 per timepoint). Control animals (surgery and anesthesia without injury) were killed at identical timepoints (n = 6 per timepoint). Tissue concentrations of NE, DA, and E were evaluated using HPLC. Following brain injury, an acute decrease was observed in DA concentrations in the injured cortex (p < 0.05) at 1 h postinjury, which persisted up to 2 weeks postinjury. Striatal concentrations of DA were significantly increased (p < 0.05) only at 6 h postinjury. Hypothalamic concentrations of DA and NE increased significantly beginning at 1 h postinjury (p < 0.05 and p < 0.05, respectively) and persisted up to 24 h for DA (p < 0.05) and 1 week (p < 0.05) for NE. These data suggest that acute alterations occur in regional concentrations of brain catecholamines following brain trauma, which may persist for prolonged periods postinjury.
Neurotoxin Quinolinic Acid Is Selectively Elevated in Spinal Cords of Rats with Experimental Allergic Encephalomyelitis
Authors: Flanagan Ellen M. , Erickson Joel B. , Viveros O. Humberto , Chang Sai Y. , Reinhard John F.
Published: July 2010

Abstract: Experimental allergic encephalomyelitis (EAE) is an autoimmune, animal model of multiple sclerosis (MS) in which demyelination and paralysis are evident. Quinolinic acid (QUIN) is a neurotoxin and endogenous N‐methyl‐d‐aspartate receptor agonist formed from tryptophan. The role of neurotoxins in general and QUIN in particular in EAE or MS is unknown. Lewis rats inoculated with myelin basic protein developed signs of EAE by day 12, were killed, and their tissues assayed for QUIN by gas chromatography with mass spectrometry. QUIN levels were significantly elevated in the more caudal regions of the spinal cords of animals with EAE. Brain, serum, and liver levels of QUIN were not altered. In a similar manner, QUIN in mylin basic protein‐injected, asymptomatic animals was not different from control animals. The time course for QUIN was similar to the neurological signs of the disorder; however, the initial elevation in QUIN occurred before the appearance of behavioral signs. Last, treatment with the glucocorticoid dexamethasone prevented both the signs of EAE and the elevation in spinal cord QUIN. It is not known whether QUIN contributes to the paralysis in EAE. However, if QUIN is pathogenic in EAE, this finding could have therapeutic implications for MS.
Localization of Various Forms of the γ Subunit of G Protein in Neural and Nonneural Tissues
Authors: Asano Tomiko , Morishita Rika , Ohashi Kayoko , Nagahama Masato , Miyake Takenori , Kato Kanefusa
Published: July 2010

Abstract: For a study of the localization of various forms of the γ subunit of G proteins, antibodies were raised in rabbits against peptides that corresponded to partial amino acid sequences of bovine γ2, γ3, γ5, and γ7. Affinity‐purified antibodies against γ2, γ3, and γ5 reacted specifically with γ2, γ3, and γ5, respectively, but the antibody against γ7 reacted with γ2, γ3, and a novel γ subunit, designated γs1, as well as with γ7. Because these antibodies reacted with the respective forms of the γ subunit from rat brain, we investigated the localization of γ subunits in the rat. γ2 and γ3 were abundant in all regions in the brain, whereas the concentration of γ5 and γ7 was relatively low with the single exception being a high concentration of γ7 in the striatum. The concentration of γ2 was consistently high during ontogenic development in the rat brain, whereas γ3 appeared about a week after birth and their concentrations then increased until a month after birth. In tissues other than the brain, γ3 was observed only in the pituitary gland, whereas γ2, γ5, and γ7 were found in a variety of tissues. In addition, most tissues contained relatively high concentrations of some other γ subunit, which was detected with an antibody against a γ7‐derived peptide and appeared to be γs1. Among cloned cells tested, γ3 was detected only in PC12 pheochromocytoma cells. Taken together, the results indicated that γ3 was expressed specifically in neuronal cells, and γs1 was the major γ subunit in most nonneural cells. γ2, γ5, and γ7 were distributed in a variety of tissues, but γ2 was dominant in the brain.