bluuebunny/crossref_metadata_2025_split huggingface dataset:
Source localization of auditory evoked potentials after cochlear implantation
Authors: Debener Stefan , Hine Jemma , Bleeck Stefan , Eyles Julie 
Published: October 2007

AbstractLittle is known about how the auditory cortex adapts to artificial input as provided by a cochlear implant (CI). We report the case of a 71‐year‐old profoundly deaf man, who has successfully used a unilateral CI for 4 years. Independent component analysis (ICA) of 61‐channel EEG recordings could separate CI‐related artifacts from auditory‐evoked potentials (AEPs), even though it was the perfectly time‐locked CI stimulation that caused the AEPs. AEP dipole source localization revealed contralaterally larger amplitudes in the P1–N1 range, similar to normal hearing individuals. In contrast to normal hearing individuals, the man with the CI showed a 20‐ms shorter N1 latency ipsilaterally. We conclude that ICA allows the detailed study of AEPs in CI users.
Comparison of the pharmacological properties of GK11 and MK801, two NMDA receptor antagonists: towards an explanation for the lack of intrinsic neurotoxicity of GK11
Authors: Vandame D. , Desmadryl G. , Becerril Ortega J. , Teigell M. , Crouzin N. , Buisson A. , Privat A. , Hirbec H. 
Published: October 2007

AbstractOver‐stimulation of NMDA receptors (NMDARs) is involved in many neurodegenerative disorders. Thus, developing safe NMDAR antagonists is of high therapeutic interest. GK11 is a high affinity uncompetitive NMDAR antagonist with low intrinsic neurotoxicity, shown to be promising for treating CNS trauma. In the present study, we investigated the molecular basis of its interaction with NMDARs and compared this with the reference molecule MK801. We show, on primary cultures of hippocampal neurons, that GK11 exhibits neuroprotection properties similar to those of MK801, but in contrast with MK801, GK11 is not toxic to neurons. Using patch‐clamp techniques, we also show that on NR1a/NR2B receptors, GK11 totally blocks the NMDA‐mediated currents but has a six‐fold lower IC50than MK801. On NR1a/NR2A receptors, it displays similar affinity but fails to totally prevent the currents. As NR2A is preferentially localized at synapses and NR2B at extrasynaptic sites, we investigated, using calcium imaging and patch‐clamp approaches, the effects of GK11 on either synaptic or extrasynaptic NMDA‐mediated responses. Here we demonstrate that in contrast with MK801, GK11 better preserve the synaptic NMDA‐mediated currents. Our study supports that the selectivity of GK11 for NR2B containing receptors accounts contributes, at least partially, for its safer pharmacological profile.
Kinase activities increase during the development of tauopathy in htau mice
Authors: Kelleher Ian , Garwood Claire , Hanger Diane P. , Anderton Brian H. , Noble Wendy 
Published: October 2007

AbstractHyperphosphorylated tau aggregates are the core constituent of neurofibrillary tangles. Recent research has shown a division between the presence of tangles, neurodegeneration and subsequent memory impairment, raising the possibility that an earlier pre‐aggregated form of tau may be toxic. To gain further insight into the relationship between abnormal forms of tau, we have analyzed pathological changes in tau during tauopathy development in tangle‐forming transgenic mice. In addition, we have quantified changes in the endogenous levels of a panel of protein kinases. We show progressive increases in aggregated tau and disease‐specific conformational change, with hyperphosphorylation occurring in an age‐dependent manner at specific sites. There were significant correlations between specific phosphorylation changes and amounts of aggregated tau and and abnormal tau conformations. Of the protein kinases tested, we found increases in phosphorylated (activated) p38 and the cyclin‐dependent kinase‐5 neuronal activators, p35 and p25, with aging, in the htau line, but not in non‐tangle‐forming control mice. Changes in tau kinases correlated with the amount of tau present in abnormal conformations and with insoluble tau in htau mice. These data suggest that cdk5 and p38 may be associated with pathological changes in wild‐type human tau during the progressive development of tauopathy.
The regulation of M1 muscarinic acetylcholine receptor desensitization by synaptic activity in cultured hippocampal neurons1
Authors: Willets Jonathon M. , Nelson Carl P. , Nahorski Stefan R. , Challiss R. A. John 
Published: October 2007

AbstractTo better understand metabotropic/ionotropic integration in neurons we have examined the regulation of M1 muscarinic acetylcholine (mACh) receptor signalling in mature (> 14 days in vitro), synaptically‐active hippocampal neurons in culture. Using a protocol where neurons are exposed to an EC50 concentration of the muscarinic agonist methacholine (MCh) prior to (R1), and following (R2) a desensitizing pulse of a high concentration of this agonist, we have found that the reduction in M1 mACh receptor responsiveness is decreased in quiescent (+tetrodotoxin) neurons and increased when synaptic activity is enhanced by blocking GABAA receptors with picrotoxin. The picrotoxin‐mediated effect on M1 mACh receptor responsiveness was completely prevented by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor blockade. Inhibition of endogenous G protein‐coupled receptor kinase 2 by transfection with the non‐Gq/11α‐binding, catalytically‐inactive D110A,K220RG protein‐coupled receptor kinase 2 mutant, decreased the extent of M1 mACh receptor desensitization under all conditions. Pharmacological inhibition of protein kinase C (PKC) activity, or chronic phorbol ester‐induced PKC down‐regulation had no effect on agonist‐mediated receptor desensitization in quiescent or spontaneously synaptically active neurons, but significantly decreased the extent of receptor desensitization in picrotoxin‐treated neurons. MCh stimulated the translocation of diacylglycerol‐ sensitive eGFP‐PKCε, but not Ca2+/diacylglycerol‐sensitive eGFP‐PKCβII in both the absence, and presence of tetrodotoxin. Under these conditions, MCh‐stimulated eGFP‐myristoylated, alanine‐rich C kinase substrate translocation was dependent on PKC activity, but not Ca2+/calmodulin. In contrast, picrotoxin‐driven translocation of myristoylated, alanine‐rich C kinase substrate was accompanied by translocation of PKCβII, but not PKCε, and was dependent on PKC and Ca2+/calmodulin. Taken together these data suggest that the level of synaptic activity may determine the different kinases recruited to regulate M1 mACh receptor desensitization in neurons.
Retinol activates tyrosine hydroxylase acutely by increasing the phosphorylation of serine40 and then serine31 in bovine adrenal chromaffin cells
Authors: Gelain Daniel P. , Moreira Jose C. F. , Bevilaqua Lia R. M. , Dickson Phillip W. , Dunkley Peter R. 
Published: October 2007

AbstractTyrosine hydroxylase is the rate‐limiting enzyme in the biosynthesis of the catecholamines. It has been reported that retinol (vitamin A) modulates tyrosine hydroxylase activity by increasing its expression through the activation of the nuclear retinoid receptors. In this study, we observed that retinol also leads to an acute activation of tyrosine hydroxylase in bovine adrenal chromaffin cells and this was shown to occur via two distinct non‐genomic mechanisms. In the first mechanism, retinol induced an influx in extracellular calcium, activation of protein kinase C and serine40 phosphorylation, leading to tyrosine hydroxylase activation within 15 min. This effect then declined over time. The retinol‐induced rise in intracellular calcium then led to a second slower mechanism; this involved an increase in reactive oxygen species, activation of extracellular signal‐regulated kinase 1/2 and serine31 phosphorylation and the maintenance of tyrosine hydroxylase activation for up to 2 h. No effects were observed with retinoic acid. These results show that retinol activates tyrosine hydroxylase via two sequential non‐genomic mechanisms, which have not previously been characterized. These mechanisms are likely to operate in vivo to facilitate the stress response, especially when vitamin supplements are taken or when retinol is used as a therapeutic agent.
Cerebral clearance of human amyloid‐β peptide (1–40) across the blood–brain barrier is reduced by self‐aggregation and formation of low‐density lipoprotein receptor‐related protein‐1 ligand complexes
Authors: Ito Shingo , Ohtsuki Sumio , Kamiie Junichi , Nezu Yasuko , Terasaki Tetsuya 
Published: October 2007

AbstractSoluble amyloid‐β peptide (Aβ) exists in the form of monomers and oligomers, and as complexes with Aβ‐binding molecules, such as low‐density lipoprotein receptor‐related protein‐1 (LRP‐1) ligands. The present study investigated the effect of self‐aggregation and LRP‐1 ligands on the elimination of human Aβ(1–40) [hAβ(1–40)] from the rat brain across the blood–brain barrier. Incubation of [125I]hAβ(1–40) monomer resulted in time‐dependent and temperature‐dependent dimer formation, and the apparent elimination rate of [125I]hAβ(1–40) dimer was significantly decreased by 92.7% compared with that of [125I]hAβ(1–40) monomer. Pre‐incubation with LRP‐1 ligands, such as activated α2‐macroglobulin (α2M), apolipoprotein E2 (apoE2), apoE3, apoE4, and lactoferrin, reduced the elimination of [125I]hAβ(1–40). By contrast, pre‐administration of the same concentration of these molecules in the rat brain did not significantly inhibit [125I]hAβ(1–40) monomer elimination. Purified [125I]hAβ(1–40)/activated α2M complex and [125I]activated α2M were not significantly eliminated from the rat brain up to 60 min. MEF‐1 cells, which have LRP‐1‐mediated endocytosis, exhibited uptake of [125I]activated α2M, and enhancement of [125I]hAβ(1–40) uptake upon pre‐incubation with apoE, suggesting that [125I]activated α2M and [125I]hAβ(1–40)/apoE complex function as LRP‐1 ligands. These findings indicate that dimerization and LRP‐1‐ligand complex formation prevent the elimination of hAβ(1–40) from the brain across the blood–brain barrier.
Split GFP complementation assay: a novel approach to quantitatively measure aggregation of tau in situ: effects of GSK3β activation and caspase 3 cleavage
Authors: Chun Wanjoo , Waldo Geoffrey S. , Johnson Gail V. W. 
Published: October 2007

AbstractTo quantitatively measure tau aggregation in situ, we established a cell model system using a split green fluorescence protein (GFP) complementation assay. In this assay the more aggregated the protein of interest the lower the GFP fluorescence. Tau microtubule‐binding domain constructs, whose aggregation characteristics have been described previously (Khlistunova et al. 2006), were used to validate the assay. The aggregation‐prone construct exhibited the lowest GFP intensity whereas the aggregation‐resistant construct showed the highest GFP intensity. To examine the role of glycogen synthase kinase 3β (GSK3β) activity and caspase 3 cleavage on tau aggregation, GFP complementation of full length (T4), caspase‐cleaved (T4C3), and pseudophosphorylated at S396/S404 (T4‐2EC) tau was examined in the presence of an active or a kinase‐dead GSK3β. Extensive phosphorylation of T4 by GSK3β resulted in increased GFP intensity. T4C3 showed neither efficient phosphorylation nor a significant GFP intensity change by GSK3β. The GFP intensity of T4‐2EC was significantly reduced by GSK3β accompanying its presence in the sarkosyl‐insoluble fraction, thus demonstrating that T4‐2EC was partitioning into aggregates. This indicates that if the majority of tau is phosphorylated at S396/S404, in combination with increased GSK3β activity, tau aggregation is favored. These data demonstrate that split GFP complementation may be a valuable approach to determine the aggregation process in living cells.
Down‐regulation of cAMP‐dependent protein kinase by over‐activated calpain in Alzheimer disease brain
Authors: Liang Zhihou , Liu Fei , Grundke‐Iqbal Inge , Iqbal Khalid , Gong Cheng‐Xin 
Published: October 2007

AbstractImpaired cognition and memory may be associated with down‐regulation of cAMP‐response element‐binding protein (CREB) in the brain in patients with Alzheimer disease, but the molecular mechanism leading to the down‐regulation is not understood. In this study, we found a selective reduction in the levels of the regulatory subunits (RIIα and RIIβ) and the catalytic subunit (Cβ) as well as the enzymatic activity of cAMP‐dependent protein kinase (PKA), which is the major positive regulator of CREB. We also observed that PKA subunits were proteolyzed by calpain and the levels of PKA subunits correlated negatively with calpain activation in the human brain. These findings led us to propose that in the brain in patients with Alzheimer disease, over‐activation of calpain because of calcium dysregulation causes increased degradation and thus decreased activity of PKA, which, in turn, contributes to down‐regulation of CREB and impaired cognition and memory.
PERMANENT GENETIC RESOURCES: Identification and characterization of 14 polymorphic microsatellite loci in the argasid tick Ornithodoros coriaceus
Authors: KIRCHOFF VERONICA S. , PEACOCK MARY M. , TEGLAS MIKE B. 
Published: October 2007

AbstractFourteen polymorphic microsatellite loci (di, tetra and di‐tetra complexes) were developed for the argasid tick Ornithodoros coriaceus. Polymorphism was assessed for 56 individuals from two populations separated by ~95 km. All loci were polymorphic (X = 7, range 3–17 alleles). All loci were in Hardy–Weinberg equilibrium except for one locus (OrC 8) in a single population (P < 0.00119, after Bonferroni correction for multiple tests).
Characterization of 25 microsatellite loci in bowhead whales (Balaena mysticetus)
Authors: HUEBINGER RYAN M. , PATTON JOHN C. , GEORGE J. CRAIG , SUYDAM ROBERT , LOUIS EDWARD E. , BICKHAM JOHN W. 
Published: October 2007

AbstractBowhead whales (Balaena mysticetus) experienced a severe demographic population bottleneck caused by commercial whaling that ceased in 1914. Aboriginal subsistence whale harvests have continued and are managed by the International Whaling Commission. In an effort to provide management advice for bowhead whales, 25 microsatellite loci were isolated from genomic DNA libraries. This panel of markers will be utilized to analyse stock structure hypotheses of current bowhead whale populations.
Sequencing breakthroughs for genomic ecology and evolutionary biology
Authors: HUDSON MATTHEW E. 
Published: October 2007

AbstractTechniques involving whole‐genome sequencing and whole‐population sequencing (metagenomics) are beginning to revolutionize the study of ecology and evolution. This revolution is furthest advanced in the Bacteria and Archaea, and more sequence data are required for genomic ecology to be fully applied to the majority of eukaryotes. Recently developed next‐generation sequencing technologies provide practical, massively parallel sequencing at lower cost and without the requirement for large, automated facilities, making genome and transcriptome sequencing and resequencing possible for more projects and more species. These sequencing methods include the 454 implementation of pyrosequencing, Solexa/Illumina reversible terminator technologies, polony sequencing and AB SOLiD. All of these methods use nanotechnology to generate hundreds of thousands of small sequence reads at one time. These technologies have the potential to bring the genomics revolution to whole populations, and to organisms such as endangered species or species of ecological and evolutionary interest. A future is now foreseeable where ecologists may resequence entire genomes from wild populations and perform population genetic studies at a genome, rather than gene, level. The new technologies for high throughput sequencing, their limitations and their applicability to evolutionary and environmental studies, are discussed in this review.
Division of labour during incubation in a woodpeckerColaptes auratuswith reversed sex roles and facultative polyandry
Authors: WIEBE KAREN L. 
Published: October 2007

The contribution of males to incubation has rarely been studied in altricial birds because the pursuit of extra mating opportunities is believed to conflict with incubation. Woodpeckers show reversed sex roles in parental care with males doing most of the nest construction, incubating and brooding of the young while females may be polyandrous. I investigated incubation by each sex at 71 monogamous and four polyandrous nests of the Northern FlickerColaptes auratus, predicting that males would contribute to incubation according to their energy reserves (body condition) whereas females would contribute based on alternate reproductive opportunities. Nest attendance was 99% with males contributing a mean of 66% of the total incubation including nocturnal incubation. The length of daytime bouts averaged about 2 h and did not differ between the sexes. Consistent with predictions of investment strategies, structurally larger males and those in poorer body condition incubated less than smaller males, perhaps because they required more recess time to forage or to conserve energy. Older females contributed less incubation than young females and polyandrous females contributed less incubation at their secondary nests than monogamous females. Incubation period, nest depredation rate and hatching success were not influenced by bout length, number of bouts or relative contribution of the sexes. Hatching success was 86% at nests of both monogamous and polyandrous females because males compensated for reduced female participation. Because incubation of the sexes is compensatory and not additive, incubation pattern did not influence short‐term reproductive success. I conclude that males invest in incubation according to their energy needs, and females may adjust their contributions based on alternate reproductive tactics.
Technology, Productivity and Public Policy*
Authors: Griffith Rachel 
Published: October 2007

AbstractThe poor productivity performance of the UK and the EU when compared with the US has been a major driver of policy reforms over the past decade. This paper considers what the evidence suggests about why we have lagged behind the US, considering among other factors the importance of globalisation and outsourcing, the role for public policy intervention and what the key drivers of growth are likely to be for the future.
Expenditure Reform in Industrialised Countries: A Case‐Study Approach*
Authors: Hauptmeier Sebastian , Heipertz Martin , Schuknecht Ludger 
Published: October 2007

AbstractThis study examines reforms of public expenditure in industrialised countries over the past two decades. We distinguish ambitious and timid reformers and analyse in detail reform experiences in eight case studies of ambitious reform episodes. We find that ambitious reform countries reduce spending on transfers, subsidies and public consumption. Such expenditure retrenchment is also typically part of a comprehensive reform package that includes improvements in fiscal institutions as well as structural and other macroeconomic reforms. The study finds that ambitious expenditure retrenchment and reform coincides with large improvements in fiscal and economic growth indicators.
Joint Taxation and the Labour Supply of Married Women: Evidence from the Canadian Tax Reform of 1988*
Authors: Crossley Thomas F. , Jeon Sung‐Hee 
Published: October 2007

AbstractThe Canadian federal tax reform of 1988 replaced a spousal tax exemption with a non‐refundable tax credit. This reduced the‘jointness’of the tax system: after the reform, secondary earners’effective‘first dollar’marginal tax rates no longer depended on the marginal tax rates of their spouses. In practice, the effective‘first dollar’marginal tax rates faced by women with high‐income husbands were particularly reduced. Using difference‐indifference estimators, we find a significant increase in labour force participation among women married to higher‐income husbands.
When Taxation Changes the Course of the Year: Fiscal‐Year Adjustments and the German Tax Reform of 2000–01*
Authors: Blasch Frank , Weichenrieder Alfons J. 
Published: October 2007

AbstractThis paper examines 157 German listed corporations that had the option of changing their fiscal year to achieve a possible tax reduction in connection with the major tax reform of 2000—01. The tax reduction from a change was larger, the larger the expected profits. However, with costs of changing the fiscal year, not all firms that expect a tax reduction from a change may do so. The paper presents empirical evidence that the propensity to change the fiscal year was significantly related to the amount of expected tax savings. This suggests that the corporate tax reduction — in combination with the special German transitory provisions — induced a deadweight loss: corporations incurred a non‐tax cost to avoid a tax cost.
On the Characterisation and Measurement of the Redistributive Effect of Agricultural Policy
Authors: Allanson Paul 
Published: October 2007

AbstractThe article proposes a coherent framework for the evaluation of the redistributive performance of agricultural policy. An illustrative study shows that the vertical stance of policy in Scotland was progressive in absolute terms, reflecting the chronic dependence of Scottish agriculture on policy transfers. Nevertheless, the overall redistributive effect of policy was to increase absolute inequality in farm incomes because of horizontal inequities in the incidence of transfers, though neither systematic discrimination between farm types nor systematic reranking was the main cause. The targeting of policy transfers could be improved by the use of indicator variables more strongly correlated with pre‐transfer incomes.
Some Consequences of the 1994–1995 Coffee Boom for Growth and Poverty Reduction in Uganda
Authors: Chant Lindsay , McDonald Scott , Verschoor Arjan 
Published: October 2007

AbstractThis paper reports a computable general equilibrium analysis that explores the consequences of the 1994–1995 increase in the international price of coffee for Uganda's economy. Evidence is found for a small effect on both medium‐term growth and poverty reduction. Aid dependence is among the reasons why this effect is not found to be larger. Major beneficiary groups are not primarily the farmers to which the windfall initially accrued, but urban wage earners and the urban self‐employed.
Factors Affecting Farmers’ Participation in Agri‐environmental Measures: A Northern Italian Perspective
Authors: Defrancesco Edi , Gatto Paola , Runge Ford , Trestini Samuele 
Published: October 2007

AbstractAgri‐environmental measures play an important role in Italian rural areas, as shown by the financial commitment to the Rural Development programmes. However, in contrast with other European Union (EU) countries, policy‐makers still have limited experience on how farmers approach environmental incentive schemes. This paper casts new light on this issue from a northern Italian perspective. The rationale of the farmers’ decision‐making process is explored using two multinomial models. The first explains the probability of non‐participation or participation in one of three specific agri‐environmental measures. The model outcomes show that labour‐intensive farming types and high dependency of household income on farming activity constrain farmers’ participation, whereas previous experience, easy‐to‐implement environmentally friendly farm practices and adequate compensation of extra costs encourage participation. The second model explores the effect of farmers’ attitudes and beliefs on their predispositions towards participation in any of the schemes. The results highlight that, besides income factors, the farm's future in the business, and the relationship with neighbouring farmers and their opinions on environmentally friendly practices all have significant effects on adoption of agri‐environmental measures. The paper concludes by suggesting that farmers’ attitudes and beliefs, as well as the local behavioural influences, have to be taken into account when designing and communicating agri‐environmental measures.