bluuebunny/crossref_metadata_2025_split huggingface dataset:
TorsinA and dystonia: from nuclear envelope to synapse
Authors: Granata Alessandra , Schiavo Giampietro , Warner Thomas T. 
Published: April 2009

AbstractA GAG deletion in the DYT1 gene is responsible for the autosomal dominant movement disorder, early onset primary torsion dystonia, which is characterised by involuntary sustained muscle contractions and abnormal posturing of the limbs. The mutation leads to deletion of a single glutamate residue in the C‐terminus of the protein torsinA, a member of the AAA+ ATPase family of proteins with multiple functions. Since no evidence of neurodegeneration has been found in DYT1 patients, the dystonic phenotype is likely to be the result of neuronal functional defect(s), the nature of which is only partially understood. Biochemical, structural and cell biological studies have been performed in order to characterise torsinA. These studies, together with the generation of several animal models, have contributed to identify cellular compartments and pathways, including the cytoskeleton and the nuclear envelope, the secretory pathway and the synaptic vesicle machinery where torsinA function may be crucial. However, the role of torsinA and the correlation between the dysfunction caused by the mutation and the dystonic phenotype remain unclear. This review provides an overview of the findings of the last ten years of research on torsinA, a critical evaluation of the different models proposed and insights towards future avenues of research.
JNK signaling in insulin‐producing cells is required for adaptive responses to stress in Drosophila
Authors: Karpac Jason , Hull‐Thompson Julie , Falleur Melody , Jasper Heinrich 
Published: April 2009

SummaryAdaptation to environmental challenges is critical for the survival of an organism. Repression of Insulin/IGF Signaling (IIS) by stress‐responsive Jun‐N‐terminal Kinase (JNK) signaling is emerging as a conserved mechanism that allows reallocating resources from anabolic to repair processes under stress conditions. JNK activation in Insulin‐producing cells (IPCs) is sufficient to repress Insulin and Insulin‐like peptide (ILP) expression in rats and flies, but the significance of this interaction for adaptive responses to stress is unclear. In this study, it is shown that JNK activity in IPCs of flies is required for oxidative stress‐induced repression of the Drosophila ILP2. It is found that this repression is required for growth adaptation to heat stress as well as adult oxidative stress tolerance, and that induction of stress response genes in the periphery is in part dependent on IPC‐specific JNK activity. Endocrine control of IIS by JNK in IPCs is thus critical for systemic adaptation to stress.
Sex differences in nutrient‐dependent reproductive ageing
Authors: Maklakov Alexei A. , Hall Matthew D. , Simpson Stephen J. , Dessmann Josephine , Clissold Fiona J. , Zajitschek Felix , Lailvaux Simon P. , Raubenheimer David , Bonduriansky Russell , Brooks Robert C. 
Published: April 2009

SummaryEvolutionary theories of aging predict that fitness‐related traits, including reproductive performance, will senesce because the strength of selection declines with age. Sexual selection theory predicts, however, that male reproductive performance (especially sexual advertisement) will increase with age. In both bodies of theory, diet should mediate age‐dependent changes in reproductive performance. In this study, we show that the sexes exhibit dramatic, qualitative differences in age‐dependent reproductive performance trajectories and patterns of reproductive ageing in the cricket Teleogryllus commodus. In females, fecundity peaked early in adulthood and then declined. In contrast, male sexual advertisement increased across the natural lifespan and only declined well beyond the maximum field lifespan. These sex differences were robust to deviations from sex‐specific dietary requirements. Our results demonstrate that sexual selection can be at least as important as sex‐dependent mortality in shaping the signal of reproductive ageing.
Ciprofloxacin decreases survival in HT‐29 cells via the induction of TGF‐β1 secretion and enhances the anti‐proliferative effect of 5‐fluorouracil
Authors: Bourikas Leonidas A , Kolios George , Valatas Vassilis , Notas George , Drygiannakis Ioannis , Pelagiadis Iordanis , Manousou Pinelopi , Klironomos Stefanos , Mouzas Ioannis A , Kouroumalis Elias 
Published: April 2009

Background and purpose: Fluoroquinolones are potent anti‐microbial agents with multiple effects on host cells and tissues. Previous studies have highlighted their pro‐apoptotic effect on human cancer cells and an immunoregulatory role in animal models of inflammatory bowel disease. We examined the effect of ciprofloxacin on proliferation, cell cycle and apoptosis of HT‐29 cells, a human colonic epithelial cell line sensitive to transforming growth factor (TGF)‐β1‐mediated growth inhibition and its role in TGF‐β1 production. We also examined the effect of ciprofloxacin on proliferation of HT‐29 cells in combination with 5‐fluorouracil (5‐FU), a well‐established pro‐apoptotic agent.Experimental approach: Using subconfluent cultures of HT‐29 and Caco‐2 cells, we studied the effect of ciprofloxacin, TGF‐β1 and 5‐FU on proliferation, apoptosis, necrosis and cell cycle. The effect of ciprofloxacin on TGF‐β1 mRNA expression and production was studied in RNA extracts and cell culture supernatants respectively, using confluent cultures.Key results: Ciprofloxacin decreased proliferation of HT‐29 cells in a concentration‐ and time‐dependent manner. This was mediated by accumulation of HT‐29 cells into the S‐phase but without any effect on apoptosis or necrosis. Additionally, ciprofloxacin enhanced the antiproliferative effect of 5‐FU. Interestingly, ciprofloxacin was found to up‐regulate TGF‐β1 production by HT‐29 cells and its anti‐proliferative effect was abolished when TGF‐β1 was blocked. Confirming this mechanism further, ciprofloxacin had no effect on Caco‐2, a human colonic epithelial cell line that lacks functional TGF‐β1 receptors.Conclusions and implications: We demonstrate a novel anti‐proliferative and immunoregulatory effect of ciprofloxacin on human intestinal epithelial cells mediated via TGF‐β1.
Does CYP2E1 play a major role in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes?
Authors: Yue Jiang , Peng Renxiu 
Published: April 2009

Isoniazid and rifampicin are first‐line anti‐tubercular drugs. In a recent paper, Shenet al.provided interesting findings that rifampicin exacerbated isoniazid toxicity in human hepatocytes but not in rat hepatocytes. The main conclusion was that the difference in cytochrome P450 2E1 (CYP2E1) induction by rifampicin between rat and human hepatocytes accounted for the difference in exacerbation of isoniazid hepatotoxicity by rifampicin. 4‐Nitrophenol hydroxylase (4‐NP) activity was the only probe of CYP2E1 activity used in the paper. The authors presented data showing that rifampicin enhanced 4‐NP activity and CYP2E1 mRNA expression in human hepatocytes, but not in rat hepatocytes. However, CYP3A also makes a significant contribution to 4‐NP activity in humans and rats, which has been confirmed by both CYP3A‐specific inducer and inhibitors. Rifampicin is a strong inducer of human CYP3A; thus, the increase in 4‐NP activity in human hepatocytes could be due to the induction of CYP3A. Rifampicin did not increase 4‐NP activities in rat hepatocytes, which could reflect a lack of the induction of rat CYP3A by rifampicin. Additionally, more experiments are needed to support the conclusion that rifampicin increased CYP2E1 mRNA expression in human hepatocytes because of the small sample size and the limitations of semi‐quantitative RT‐PCR. The study by Shenet al.suggests that another drug‐metabolizing enzyme rather than CYP2E1 could be involved in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes.The 2008 paper by Shenet al.is available fromhttp://www3.interscience.wiley.com/cgi‐bin/fulltext/121667602/PDFSTART
Effects of zotepine on extracellular levels of monoamine, GABA and glutamate in rat prefrontal cortex
Authors: Yamamura S , Ohoyama K , Hamaguchi T , Nakagawa M , Suzuki D , Matsumoto T , Motomura E , Tanii H , Shiroyama T , Okada M 
Published: April 2009

Background and purpose: The atypical antipsychotic drug, zotepine, is effective in treatment of schizophrenia and acute mania, but the incidence of seizures during treatment is higher than with other antipsychotics. In addition, the mechanisms underlying the clinical actions of zotepine remain uncharacterized.Experimental approach: The effects of intraperitoneal administration of zotepine and haloperidol on the extracellular levels of noradrenaline, dopamine, 5‐HT, GABA, and glutamate in the medial prefrontal cortex (mPFC) were compared. Neuronal activities induced by each drug in the ventral tegmental area (VTA), locus coeruleus (LC), dorsal raphe nucleus (DRN) and mediodorsal thalamic nucleus (MTN) were also analysed.Key results: Haloperidol did not affect extracellular neurotransmitter levels in the mPFC. In contrast, zotepine activated neuronal activities in all nuclei and increased the extracellular levels of noradrenaline, dopamine, GABA, and glutamate in the mPFC, but not 5‐HT levels. The zotepine‐stimulated neuronal activity in the VTA, LC, DRN and MTN enhanced the release of dopamine, noradrenaline, 5‐HT, glutamate and GABA in the mPFC, although the enhanced GABAergic transmission possibly inhibited noradrenaline, dopamine and 5‐HT release. The other afferent to mPFC, which releases dopamine and noradrenaline, was partially insensitive to GABAergic inhibition, but possibly received stimulatory AMPA/glutamatergic regulation from the MTN.Conclusions and implications: Our results indicated that the positive interaction between prefrontal catecholaminergic transmission and AMPA/glutamatergic transmission from MTN might explain the regulatory effects of zotepine on neurotransmitter release. A mechanism is suggested to account for the pharmacological profile of this atypical antipsychotic and for its pro‐convulsive action.British Journal of Pharmacology(2009)157,656–665; doi:10.1111/j.1476‐5381.2009.00175.x; published online 9 April 2009
Effect of K+and Rb+on the action of verapamil on a voltage‐gated K+channel,hKv1.3: implications for a second open state?
Authors: Kuras Z , Grissmer S 
Published: April 2009

Background and purpose: Verapamil blocks current through the voltage‐gated K+channel Kv1.3 in the open and inactivated state of the channel but not the closed state. The binding site for verapamil was proposed to be close to the selectivity filter and the occupancy of the selectivity filter might therefore influence verapamil affinity.Experimental approach: We investigated the influence of intra‐ and extracellular K+and Rb+on the effect of verapamil by patch‐clamp studies, in COS‐7 cells transfected withhKv1.3 channels.Key results: Verapamil affinity was highest in high intracellular K+concentrations ([K+]i) and lowest in low [Rb+]i, indicating an influence of intracellular cations on verapamil affinity. Experiments with a mutant channel (H399T), exhibiting a strongly reduced C‐type inactivated state, demonstrated that part of this changed verapamil affinity in wild‐type channels could be caused by altered C‐type inactivation. External K+and Rb+could influence verapamil affinity by a voltage‐dependent entry into the channel thereby modifying the verapamil off‐rate and in addition causing a voltage‐dependent verapamil off‐rate.Conclusions and implications: Recovery from verapamil block was mainly due to the voltage‐dependent closing of channels (state‐dependent block), implying a second open state of the channel. This hypothesis was confirmed by the dependency of the tail current time course on duration of the prepulse. We conclude that the wild‐typehKv1.3 channel undergoes at least two different conformational changes before finally closing with a low verapamil affinity in one open state and a high verapamil affinity in the other open state.
Labour Market Adjustment and Intra‐Industry Trade: The Effects of Association on the Hungarian Food Industry
Authors: Ferto Imre 
Published: April 2009

Abstract The structure of Hungary’s food trade expansion over the period 1995–2003 and its implications for labour market adjustment are examined. The contributions of the paper are threefold. First, we test the sensitivity of results to the choice of measurement and their implications for the results. Second, we introduce more industry‐specific control variables. Third, we distinguish the short‐ and long‐run adjustment effects. Our results provide some support for the smooth‐adjustment hypothesis of intra‐industry trade. Estimations confirm that industry‐specific variables may have a significant effect on adjustment costs.
The Missionary Impact: The Northern Transvaal in the Late Nineteenth Century
Authors: Kirkaldy Alan 
Published: April 2009

AbstractDuring the nineteenth century, missionaries were largely unsuccessful in making, and keeping, a significant number of converts in the Northern Transvaal. In addition, in marked contrast to commonly‐held assumptions, much of the early work of evangelisation was performed by African converts, rather than white missionaries. The introduction of western medicine, education and literacy did not achieve the ends envisaged by the missionaries. The majority of people did not abandon their culture and adopt the new religions and cultural ways. Africans nevertheless took these new tools and used them in ways unforeseen by the missionaries. A blending of African and Western ways took place which led to cultural transformation.
Alexander the Great in Current Scholarship
Authors: Anson Edward M. 
Published: April 2009

AbstractInterest in Alexander the Great has never flagged from the time of his death until the present day. The bibliography of Alexander the Great continues to grow at near exponential rates. He was a commander of outstanding ability whose legacy was a world forever changed. However, plagued by a dearth of contemporary sources, scholars still debate his goals, his methods, and his true legacy. Did he envision and work towards a world where the races would be fused into one? Or was he an insatiable conqueror whose values were those of a Genghis Khan or a Tamarlane? Was his empire built on expediency or was it an attempt at a new world order under an absolute monarch. Finally, did Alexander order his own deification, and was this the result of practical administrative and political calculations, or was it the consequence of growing megalomaniacy. All of these interpretations have modern scholarly adherents, although some have come to dominate most current scholarship.
Factor Structure and Concurrent Validity of the Obsessive Compulsive Drinking Scale in a Group of Alcohol‐Dependent Subjects of Mexico City
Authors: Cordero Marta , Solís Luís , Cordero Roberto , Torruco Mario , Cruz‐Fuentes Carlos 
Published: April 2009

Background:  Obsessive thoughts and compulsive drinking behaviors have been proposed as key factors associated with the loss of control over alcohol consumption experienced by alcohol‐dependent patients. The self‐report 14‐item Obsessive Compulsive Drinking Scale (OCDS; Anton et al., 1995) was designed in order to rate these features.Methods:  A Spanish‐translated version of the OCDS was applied to a group of 159 alcohol‐dependent subjects while in abstinence, and data were analyzed in order to evaluate the factor structure and concurrent validity of the scale.Results:  Several solutions were explored after applying the principal factor analysis to the data. The most plausible result was obtained after excluding the items on quantity and frequency of drinking. This model explaining 56.9% of the variance included 2 factors: obsessive thoughts related to drinking and interference/behaviors related to drinking. Additionally, OCDS scores were significantly correlated with measures for the Alcohol Dependence Scale, number of DSM‐IV criteria met for alcohol dependence as well as the number of days in a week engaged in heavy drinking, indicating concurrent validity.Conclusions:  Our results support the use of OCDS as a valid self‐rated instrument that can be broadly applied in research and treatment settings. However, its current version includes questions that may not represent the core concept of craving. The abridged 12‐item version of the scale (excluding the items on drinking habits) maintains good psychometrics features and seems to be adequate when different cognitive and behavioral dimensions are explored.
Disparity Between Tonic and Phasic Ethanol‐Induced Dopamine Increases in the Nucleus Accumbens of Rats
Authors: Robinson Donita L. , Howard Elaina C. , McConnell Scott , Gonzales Rueben A. , Wightman R. Mark 
Published: April 2009

Background: Dopamine concentrations in the nucleus accumbens fluctuate on phasic (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol increases tonic concentrations of dopamine, but its effect on subsecond dopamine transients has not been fully explored.Methods: We measured tonic and phasic dopamine fluctuations in the nucleus accumbens of rats in response to ethanol (within‐subject cumulative dosing, 0.125 to 2 g/kg, i.v.).Results: Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between‐site effects reflected specific pharmacology at that recording site.Conclusions: These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens.
The Impact of Underage Drinking Laws on Alcohol‐Related Fatal Crashes of Young Drivers
Authors: Fell James C. , Fisher Deborah A. , Voas Robert B. , Blackman Kenneth , Tippetts A. Scott 
Published: April 2009

Background:  This study used a pre‐ to post‐design to evaluate the influence on drinking‐and‐driving fatal crashes of 6 laws directed at youth aged 20 and younger and 4 laws targeting all drivers.Methods:  Data on the laws were drawn from the Alcohol Policy Information System data set (1998 to 2005), the Digests of State Alcohol Highway Safety Related Legislation (1983 to 2006), and the Westlaw database. The Fatality Analysis Reporting System data set (1982 to 2004) was used to assess the ratio of drinking to nondrinking drivers involved in fatal crashes [fatal crash incidence ratio (CIR)]. The data were analyzed using structural equation modeling techniques.Results:  Significant decreases in the underage fatal CIR were associated with presence of 4 of the laws targeting youth (possession, purchase, use and lose, and zero tolerance) and 3 of the laws targeting all drivers (0.08 blood alcohol concentration illegal per se law, secondary or upgrade to a primary seat belt law, and an administrative license revocation law). Beer consumption was associated with a significant increase in the underage fatal CIR. The direct effects of laws targeting drivers of all ages on adult drinking drivers aged 26 and older were similar but of a smaller magnitude compared to the findings for those aged 20 and younger. It is estimated that the 2 core underage drinking laws (purchase and possession) and the zero tolerance law are currently saving an estimated 732 lives per year controlling for other exposure factors. If all states adopted use and lose laws, an additional 165 lives could be saved annually.Conclusions:  These results provide substantial support for the effectiveness of under age 21 drinking laws with 4 of the 6 laws examined having significant associations with reductions in underage drinking‐and‐driving fatal crashes. These findings point to the importance of key underage drinking and traffic safety laws in efforts to reduce underage drinking‐driver crashes.
IgA Immune Responses Against Acetaldehyde Adducts and Biomarkers of Alcohol Consumption in Patients with IgA Glomerulonephritis
Authors: Kaartinen Kati , Niemelä Onni , Syrjänen Jaana , Alatalo Päivikki , Pörsti Ilkka , Harmoinen Aimo , Pasternack Amos , Huhtala Heini , Mustonen Jukka 
Published: April 2009

Background:  The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo‐antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined.Methods:  A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self‐reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate‐deficient transferrin (CDT), glutamyl transferase, γ‐CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde–protein adducts.Results:  In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and γ ‐CDT, p < 0.05. In the reference population, all biomarkers and anti‐adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti‐adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self‐reported ethanol intake.Conclusions:  These data indicate high levels of IgA antibodies against acetaldehyde‐derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti‐adduct immune responses in IgAGN patients are warranted.
Art Museum Attendance, Public Funding, and the Business Cycle
Authors: Skinner Sarah J. , Ekelund, Jr. Robert B. , Jackson John D. 
Published: April 2009

AbstractThere are a number of important problems in contemporary museum finance, and this article identifies yet another possible difficulty. An aggregate statistical measure of museum attendance is calculated in this research and the attendance measure is shown to be countercyclical in nature. When set against federal and other allocations to museums, which are clearly pro‐cyclical in nature, an attendance “disease” may be at least tentatively identified. Efficiency criteria, of course, require that costs are covered in real time. We find, however, that, despite the likelihood that museum attendance is income‐elastic and a normal good, attendance varies countercyclically with the business cycle. We suggest that one possible explanation for this phenomenon is that a positive substitution effect on demand outweighs the income effect on demand for museum attendance over the cycle. From a policymaking perspective, these results call for a longer range planning horizon, that is, one that includes the full business cycle rather than just the financial year, as is the current U.S. government practice.