bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of psychostimulant‐induced signaling and gene expression in the striatum
Authors: McGinty Jacqueline F. , Shi Xiangdang D. , Schwendt Marek , Saylor Alicia , Toda Shigenobu 
Published: February 2008

J. Neurochem. (2008) 104, 1440–1449.AbstractAmphetamine (AMPH) and cocaine are indirect dopamine agonists that activate multiple signaling cascades in the striatum. Each cascade has a different subcellular location and duration of action that depend on the strength of the drug stimulus. In addition to activating D1 dopamine‐Gs‐coupled‐protein kinase A signaling, acute psychostimulant administration activates extracellular‐regulated kinase transiently in striatal cells; conversely, inhibition of extracellular‐regulated kinase phosphorylation decreases the ability of psychostimulants to elevate locomotor behavior and opioid peptide gene expression. Moreover, a drug challenge in rats with a drug history augments and prolongs striatal extracellular‐regulated kinase phosphorylation, possibly contributing to behavioral sensitization. In contrast, AMPH activates phosphoinositide‐3 kinase substrates, like protein kinase B/Akt, only in the nuclei of striatal cells but this transient increase induced by AMPH is followed by a delayed decrease in protein kinase B/Akt phosphorylation whether or not the rats have a drug history, suggesting that the phosphoinositide‐3 kinase pathway is not essential for AMPH‐induced behavioral sensitization. Chronic AMPH or cocaine also alters the regulation of inhibitory G protein‐coupled receptors in the striatum, as evident by a prolonged decrease in the level of regulator of G protein signaling 4 after non‐contingent or contingent (self‐administered) drug exposure. This decrease is exacerbated in behaviorally sensitized rats and reversed by re‐exposure to a cocaine‐paired environment. A decrease in regulator of G protein signaling 4 levels may weaken its interactions with metabotropic glutamate receptor 5, Gαq, and phospholipase C β that may enhance drug‐induced signaling. Alteration of these protein–protein interactions suggests that the striatum responds to psychostimulants with a complex molecular repertoire that both modulates psychomotor effects and leads to long‐term neuroadaptations.
Osmotic swelling characteristics of glial cells in the murine hippocampus, cerebellum, and retina in situ
Authors: Hirrlinger Petra G. , Wurm Antje , Hirrlinger Johannes , Bringmann Andreas , Reichenbach Andreas 
Published: February 2008

AbstractGlial cells are proposed to play a major role in the ionic and osmotic homeostasis in the CNS. Swelling of glial cells contributes to the development of edema in neural tissue under pathological conditions such as trauma and ischemia. In this study, we compared the osmotic swelling characteristics of murine hippocampal astrocytes, cerebellar Bergmann glial cells, and retinal Müller glial cells in acutely isolated tissue slices in response to hypoosmotic stress and pharmacological blockade of Kir channels. Hypoosmotic challenge induced an immediate swelling of somata in the majority of Bergmann glial cells and hippocampal astrocytes investigated, whereas Müller cell bodies displayed a substantial delay in the onset of swelling and hippocampal astroglial processes remained unaffected. Blockade of Kir channels under isoosmotic conditions had no swelling‐inducing effect in Müller cell somata but caused a swelling in brain astrocytic somata and processes. Blockade of Kir channels under hypoosmotic conditions induced an immediate and strong swelling in Müller cell somata, but had no cumulative effect to brain astroglial somata. No regulatory volume decrease could be observed in all cell types. The data suggest that Kir channels are differently implicated in cell volume homeostasis of retinal Müller cells and brain astrocytes and that Müller cells and brain astrocytes differ in their osmotic swelling properties.
Structure‐activity analysis of ginkgolide binding in the glycine receptor pore
Authors: Heads Judith A. , Hawthorne Rebecca L. , Lynagh Timothy , Lynch Joseph W. 
Published: February 2008

AbstractGinkgolides, active constituents of Ginkgo biloba extracts, potently block the glycine receptor chloride channel (GlyR). Ginkgolides A, B, C and J are structurally similar, varying only by the presence or absence of oxygens at their R1 and R2 positions. The aim of this study was to understand how variable ginkgolide groups bind to pore‐lining 2′ and 6′ residues in the α1 GlyR. Ginkgolide potency was not affected by G2′A or G2′S mutations, suggesting 2′ residues are not important for ginkgolide coordination. Analysis of the α1T6′S GlyR suggests that ginkgolides bind to this receptor via hydrogen bonds between T6′S and ginkgolide R1 hydroxyls. The abolition of block by the T6′A and T6′V mutations but not by the T6′S mutation implies the existence a second transmembrane domain α‐helical kink formed by hydrogen bonding between 6′ threonine and serine sidechains and backbone carbonyl oxygens. We also found that ginkgolide A binds in different orientations in the closed and open states of a mutant GlyR, possibly reflecting its enhanced flexibility relative to other ginkgolides. Together these results indicate that small variations in ginkgolide structure or pore structure can lead to drastic potency variations. This property may be exploited to create improved pharmacological probes for discriminating among anionic Cys‐loop receptor isoforms with 6′ structural variations.
In vitro high affinity α‐synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain1
Authors: Ye Liang , Velasco Ana , Fraser Graham , Beach Thomas G. , Sue Lucia , Osredkar Tracy , Libri Vincenzo , Spillantini Maria Grazia , Goedert Michel , Lockhart Andrew 
Published: February 2008

AbstractAmyloid containing deposits are a defining neuropathological feature of a wide range of dementias and movement disorders. The positron emission tomography tracer PIB (Pittsburgh Compound‐B, 2‐[4′‐(methylamino)phenyl]‐6‐hydroxybenzothiazole) was developed to target senile plaques, an amyloid containing pathological hallmark of Alzheimer’s disease, formed from the amyloid‐β peptide. Despite the fact that PIB was developed from the pan‐amyloid staining dye thioflavin T, no detailed characterisation of its interaction with other amyloid structures has been reported. In this study, we demonstrate the presence of a high affinity binding site (Kd∼4 nM) for benzothiazole derivatives, including [3H]‐PIB, on α‐synuclein (AS) filaments generated in vitro, and further characterise this binding site through the use of radioligand displacement assays employing 4‐N‐methylamino‐4′‐hydroxystilbene (SB13) (Ki = 87 nM) and 2‐(1‐{6‐[(2‐fluoroethyl(methyl)amino]‐2‐naphthyl}ethylidene)malononitrile (FDDNP) (Ki = 210 nM). Despite the presence of a high‐affinity binding site on AS filaments, no discernible interaction of [3H]‐PIB was detected with amygdala sections from Parkinson’s disease cases containing frequent AS‐immunoreactive Lewy bodies and related neurities. These findings suggest that the density and/or accessibility of AS binding sites in vivo are significantly less than those associated with amyloid‐β peptide lesions. Lewy bodies pathology is therefore unlikely to contribute significantly to the retention of PIB in positron emission tomography imaging studies.
The separation of antagonist from agonist effects of trisubstituted purines on CaV2.2 (N‐type) channels
Authors: Buraei Zafir , Elmslie Keith S. 
Published: February 2008

AbstractDihydropyridines can affect L‐type calcium channels (CaV1) as either agonists or antagonists. Seliciclib or R‐roscovitine, a 2,6,9‐trisubstituted purine, is a potent cyclin‐dependent kinase inhibitor that induces both agonist and antagonist effects on CaV2 channels (N‐, P/Q‐ and R‐type). We studied the effects induced by various trisubstituted purines on CaV2.2 (N‐type) channels to learn about chemical structure–function relationships. We found that S‐roscovitine and R‐roscovitine showed similar potency to inhibit, but agonist activity of S‐roscovitine required at least a 20‐fold higher concentration, suggesting stereospecificity of the agonist‐binding site. The testing of other trisubstituted purines showed a correlation between CaV2.2 inhibition and cyclin‐dependent kinase affinity that broke down after determining that a chemically unrelated inhibitor, kenpaullone, was a poor CaV2.2 inhibitor, and a kinase inactive analog (dimethylamino‐olomoucine; DMAO) was a strong inhibitor, which together support a kinase independent effect. In fact, like dihydropyridine‐induced L‐channel inhibition, R‐roscovitine left‐shifted the closed‐state inactivation versus voltage relationship, which suggests that inhibition results from CaV2 channels moving into the inactivated state. Trisubstituted purine antagonists could become clinically important drugs to treat diseases, such as heart failure and neuropathic pain that result from elevated CaV2 channel activity.
Expression of multiple AQP4 pools in the plasma membrane and their association with the dystrophin complex
Authors: Nicchia Grazia Paola , Cogotzi Laura , Rossi Andrea , Basco Davide , Brancaccio Andrea , Svelto Maria , Frigeri Antonio 
Published: February 2008

AbstractAltered aquaporin‐4 (AQP4) expression has been reported in brain edema, tumors, muscular dystrophy, and neuromyelitis optica. However, the plasma membrane organization of AQP4 and its interaction with proteins such as the dystrophin‐associated protein complex are not well understood. In this study, we used sucrose density gradient ultracentrifugation and 2D blue native/sodium dodecyl sulfate–polyacrylamide gel electrophoresis and showed the expression of several AQP4 multi‐subunit complexes (pools) of different sizes, ranging from ≫ 1 MDa to ∼500 kDa and containing different ratios of the 30/32 kDa AQP4 isoforms, indicative of orthogonal arrays of particles of various sizes. A high molecular weight pool co‐purified with dystrophin and β‐dystroglycan and was drastically reduced in the skeletal muscle of mdx3cv mice, which have no dystrophin. The number and size of the AQP4 pools were the same in the kidney where dystrophin is not expressed, suggesting the presence of dystrophin‐like proteins for their expression. We found that AQP2 is expressed only in one major pool of ∼500 kDa, indicating that the presence of different pools is a peculiarity of AQP4 rather than a widespread feature in the AQP family. Finally, in skeletal muscle caveolin‐3 did not co‐purify with any AQP4 pool, indicating the absence of interaction of the two proteins and confirming that caveolae and orthogonal arrays of particles are two independent plasma membrane microdomains. These results contribute to a better understanding of AQP4 membrane organization and raise the possibility that abnormal expression of specific AQP4 pools may be found in pathological states.
Transcriptional activation of human mu‐opioid receptor gene by insulin‐like growth factor‐I in neuronal cells is modulated by the transcription factor REST
Authors: Bedini Andrea , Baiula Monica , Spampinato Santi 
Published: February 2008

AbstractThe human mu‐opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. We investigated whether insulin‐like growth factor I (IGF‐I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1‐luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma‐derived SH‐SY5Y cells and PC12 cells. In the former, endogenous levels of human mu‐opioid receptor (hMOPr) mRNA were evaluated by real‐time PCR. IGF‐I up‐regulated OPRM1 transcription in: PC12 cells lacking REST, in SH‐SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down‐regulated in retinoic acid‐differentiated cells. IGF‐I activates the signal transducer and activator of transcription‐3 signaling pathway and this transcription factor, binding to the signal transducer and activator of transcription‐1/3 DNA element located in the promoter, increases OPRM1 transcription. We propose that a reduction in REST is a critical switch enabling IGF‐I to up‐regulate hMOPr. These findings help clarify how hMOPr expression is regulated in neuronal cells.
IL‐1F5 mediates anti‐inflammatory activity in the brain through induction of IL‐4 following interaction with SIGIRR/TIR8
Authors: Costelloe Ceire , Watson Melanie , Murphy Aine , McQuillan Keith , Loscher Christine , Armstrong Michelle E. , Garlanda Cecilia , Mantovani Alberto , O’Neill Luke A. J. , Mills Kingston H. G. , Lynch Marina A. 
Published: February 2008

AbstractSimilarity in structure and sequence homology has led to the identification of new members of the interleukin‐1 (IL‐1) ligand and receptor superfamilies. IL‐1F6, IL‐1F8 and IL‐1F9 have been shown to signal through IL‐1R‐related protein 2 and IL‐1 receptor accessory protein leading to activation of NFκB, while IL‐1F7 and IL‐1F10 interact with the IL‐18 receptor and the soluble IL‐1 receptor type I respectively. In contrast, identification of a biological role for IL‐1F5 has remained elusive, with conflicting data relating to its possible ability to antagonize IL‐1F9‐stimulated activation of NFκB in Jurkat cells transfected with IL‐1R‐related protein 2. In this study, we set out to investigate a possible role for IL‐1F5 in the brain and report that it antagonizes the inflammatory effects of IL‐1β and lipopolysaccharide (LPS) in vivo and in vitro including the inhibitory effect on long‐term potentiation (LTP) in rat hippocampus. We demonstrate that IL‐1F5 induces IL‐4 mRNA and protein expression in glia in vitro and enhances hippocampal expression of IL‐4 following intracerebroventricular (i.c.v.) injection. The inhibitory effect of IL‐1F5 on LPS‐induced IL‐1β is attenuated in cells from IL‐4‐defective (IL−4−/− mice). Our findings suggest that IL‐1F5 mediates anti‐inflammatory effects through its ability to induce IL‐4 production and that this is a consequence of its interaction with the orphan receptor, single Ig IL‐1R‐related molecule (SIGIRR)/TIR8, as the effects were not observed in SIGIRR−/− mice. In contrast to its effects in brain tissue, IL‐1F5 did not attenuate LPS‐induced changes, or up‐regulated IL‐4 in macrophages or dendritic cells, suggesting that the effect is confined to the brain.
Impacts of Market Reform on Spatial Volatility of Maize Prices in Tanzania
Authors: Kilima Fredy T. M. , Chung Chanjin , Kenkel Phil , Mbiha Emanuel R. 
Published: February 2008

AbstractMaize is one of the major staples and cash crops for many Tanzanians. Excessive volatility of maize prices destabilises farm income in maize‐growing regions and is likely to jeopardise nutrition and investment in many poor rural communities. This study investigates whether market reform policies in Tanzania have increased the volatility of maize prices, and identifies regional characteristics that can be attributed to the spatial price volatility. To achieve the objectives, an autoregressive conditional heteroskedasticity in mean (ARCH‐M) model is developed and estimated in this study. Results show that the reforms have increased farm‐gate prices and overall price volatility. Maize prices are lower in surplus and less developed regions than those in deficit and developed regions. Results also show that the developed and maize‐deficit regions, and regions bordering other countries have experienced less volatile prices than less developed, maize‐surplus and non‐bordering regions. Our findings indicate that investments in communication and transportation infrastructures from government and donor countries are likely to increase inter‐regional and international trade, thereby reducing the spatial price volatility in Tanzanian maize prices in the long run.
Forecasting the Adoption of GM Oilseed Rape: Evidence from a Discrete Choice Experiment in Germany
Authors: Breustedt Gunnar , Müller‐Scheeßel Jörg , Latacz‐Lohmann Uwe 
Published: February 2008

AbstractThis paper explores farmers’ willingness to adopt genetically modified (GM) oilseed rape prior to its commercial release and estimates the ‘demand’ for the new technology. The analysis is based upon choice experiments with 202 German arable farmers. A multinomial probit estimation reveals that GM attributes such as gross margin, expected liability from cross pollination, or flexibility in returning to conventional oilseed rape significantly affect the likelihood of adoption. Neighbouring farmers’ attitudes towards GM cropping and a number of farmer and farm characteristics were also found to be significant determinants of prospective adoption. Demand simulations suggest that adoption rates are very sensitive to the profit difference between GM and non‐GM rape varieties. A monopolistic seed price would substantially reduce demand for the new technology. A monopolistic seed supplier would reap between 45% and 80% of the GM rent, and the deadweight loss of the monopoly would range between 15% and 30% of that rent. The remaining rent for farmers may be too small to outweigh possible producer price discounts resulting from the costs of segregating GM and non‐GM oilseed rape along the supply chain.
The Spatial Integration of Paddy Markets in Vietnam
Authors: Baulch Bob , Hansen Henrik , Trung Le Dang , Tam Tran Ngo Minh 
Published: February 2008

AbstractThis paper examines whether there is spatial integration between and within paddy markets in the north and south of Vietnam. The empirical model developed uses estimates of transfer costs to generalise Ravallion's model of spatial market integration to allow for threshold effects. A sequential testing strategy is used to test for market segmentation, the number of thresholds, long‐run integration, informational efficiency and the Law of One Price within an error‐correction framework. We find neither threshold effects nor weak evidence of paddy market integration between northern and southern Vietnam. There is, however, evidence of both threshold effects and stronger market integration within the Red and Mekong River deltas. Whenever price spreads exceed their thresholds, at least 60% of price changes are transmitted between regional markets within a month. Nonetheless, the instantaneous version of the Law of One Price only holds for a few regimes and market pairs. These results suggest that national level policies cannot be relied upon to stabilise or support paddy prices in Vietnam. Instead, policies need to be designed with the specific production, consumption and marketing characteristics of northern and southern Vietnam in mind.
Cost Structure and Vertical Integration between Farming and Processing
Authors: Kvaløy Ola , Tveterås Ragnar 
Published: February 2008

AbstractIn several food‐producing sectors, we observe vertical integration between the farming and processing stages. The salmon industry, which has motivated this paper, has seen a rise in large vertically integrated companies over the last decade, with direct ownership of production activities including hatcheries, fish processing and exporting. Both the farming and processing stages have become more capital intensive, which has led to a steeper U‐shaped average cost (AC) curve. In this paper we present a theoretical link between this technological shift and vertical integration: in a repeated game model of relational contracting, we show that when the AC curve is sufficiently steep, then processors and farmers are more likely to vertically integrate. The reason is that steep AC curves make it costly to deviate from the optimal production scale, which in turn makes processors more vulnerable to hold‐up and opportunistic behaviours from its suppliers.
Evaluating the Potential of Index Insurance Schemes to Reduce Crop Yield Risk in an Arid Region
Authors: Breustedt Gunnar , Bokusheva Raushan , Heidelbach Olaf 
Published: February 2008

AbstractWe evaluate yield risk reduction through weather index, area yield index and farm yield insurance contracts for wheat farms in Kazakhstan by employing data from 1980 to 2002. We use the usual mean variance (MV) approach and also a second‐degree stochastic dominance (SSD) criterion. While MV is not necessarily consistent with the expected utility (EU) theory, SSD results only in a minimum but EU‐consistent benefit from insuring. Differences in the estimation results for both approaches underline the advantage of applying both criteria to analyse the risk‐reducing potential of crop insurance. Bootstrapping results show that none of the analysed insurance schemes provides statistically significant risk reduction for every single farm. In addition, weather‐based index insurance is found to provide less risk reduction than area yield insurance based on the rayon (county) yield. Moreover, rayon yield index insurance can reduce yield risk more effectively for Kazakhstan's wheat producers than farm yield insurance with a low strike yield.
Modelling the Crop Variety Demand of Semi‐Subsistence Households: Bananas in Uganda
Authors: Edmeades Svetlana , Phaneuf Daniel J. , Smale Melinda , Renkow Mitch 
Published: February 2008

AbstractWe propose an approach to model the derived demand for crop varieties among semi‐subsistence farmers in a developing economy, and apply it to smallholder banana producers in Uganda. We model variety planting decisions as being composed of an extensive margin decision to grow a subset of locally available varieties (variety choice); and an intensive margin decision about the scale or extent of variety cultivation per farm (variety demand). We estimate variety demand equations using a more complete representation of the choice set upon which observed planting decisions are made. Computed elasticities of variety demand with respect to variety attributes indicate that the relative importance of consumption and production attributes varies by location and proximity to markets, from which we draw implications for the social and economic impact of crop improvement. The approach that we propose has broad appeal for analysing adoption decisions for modern or traditional varieties of both major and minor crops in developing countries.
Dental caries and body mass index by socio‐economic status in Swedish children
Authors: Gerdin Elisabeth Wärnberg , Angbratt Marianne , Aronsson Kerstin , Eriksson Elin , Johansson Ingegerd 
Published: February 2008

AbstractObjectives:  The aim of the present study was to evaluate the association between dental caries, childhood body mass index (BMI), and socioeconomic status in Swedish children.Methods:  The study cohort consisted of 2303 10‐year‐old children with data on socioeconomic status, BMI at 4, 5, 7 and 10 years of age, and caries at 6, 10 and 12 years of age. Anthropometric measures were carried out by trained nurses according to standardized routines. The occurrence of caries was registered from county records, and the children were classified into one of five socioeconomic clusters based on their census registration address.Results:  Caries prevalence decreased with increasing socioeconomic status at all ages, whereas childhood BMI and proportion of overweight/obese children were unrelated to socioeconomic status. Obese, but not overweight, children had more caries affected teeth than non‐obese, and BMI had an independent, though weak, effect on caries variation in multiple regression. Interestingly, overweight/obese 4‐year‐olds, who had normal body weight at 5, 7 and 10 years of age, had significantly less caries than children who had normal body weight from 4 to 10 years of age.Conclusions:  Overweight and caries prevalence are significantly associated in Swedish children. However, the association is weak. Nevertheless, the concept that child dental services and child welfare services can benefit from joint programs is supported.