bluuebunny/crossref_metadata_2025 huggingface dataset:
THE POWER OF EUROPEAN FATWAS: THE MINORITY FIQH PROJECT AND THE MAKING OF AN ISLAMIC COUNTERPUBLIC
Authors: Caeiro Alexandre
Published: July 2010

This paper seeks to understand and contextualize the work of the European Council for Fatwa and Research, an institution committed to the elaboration of a fiqh of minorities through the production and dissemination at regular intervals of fatwas for Muslims living in Europe. Drawing closely on the work of Michael Warner, I suggest that the minority fiqh project may be best understood as the result of a performative conjunction between a particular tension—the tension between the cultivation of a pious subjectivity in tune with the temporalities of the global Islamic Revival and the perceived necessity to integrate Muslims into local European contexts—and a specific relation to public discourse. The paper argues that the Islamic counterpublic brought about by the European Council for Fatwa and Research's mode of interpellation of European Muslim subjects finds in the Muslim reader its paradigmatic figure. It concludes by suggesting some of the ways in which the Islamic counterpublic may be authorized or disrupted both by its Muslim addressees and by other discourses articulated in mainstream European publics.
On Lagrangian drift in shallow-water waves on moderate shear
Authors: PHILLIPS W. R. C. , DAI A. , TJAN K. K.
Published: July 2010

The Lagrangian drift in anO(ϵ) monochromatic wave field on a shear flow, whose characteristic velocity isO(ϵ) smaller than the phase velocity of the waves, is considered. It is found that although shear has only a minor influence on drift in deep-water waves, its influence becomes increasingly important as the depth decreases, to the point that it plays a significant role in shallow-water waves. Details of the shear flow likewise affect the drift. Because of this, two temporal cases common in coastal waters are studied, viz. stress-induced shear, as would arise were the boundary layer wind-driven, and a current-driven shear, as would arise from coastal currents. In the former, the magnitude of the drift (maximum minus minimum) in shallow-water waves is increased significantly above its counterpart, viz. the Stokes drift, in like waves in otherwise quiescent surroundings. In the latter, on the other hand, the magnitude decreases. However, while the drift at the free surface is always oriented in the direction of wave propagation in stress-driven shear, this is not always the case in current-driven shear, especially in long waves as the boundary layer grows to fill the layer. This latter finding is of particular interest vis-à-vis Langmuir circulations, which arise through an instability that requires differential drift and shear of the same sign. This means that while Langmuir circulations form near the surface and grow downwards (top down), perhaps to fill the layer, in stress-driven shear, their counterparts in current-driven flows grow from the sea floor upwards (bottom up) but can never fill the layer.
Re-Mapping the Nation: Cartography, Geographical Knowledge and Ecuadorean Multiculturalism
Authors: RADCLIFFE SARAH A.
Published: July 2010

Starting from an understanding that maps of an entire nation-state territory reflect and regulate state projects and expressions of national identity, rather than providing detailed technical information for decision making, this paper examines the national maps of race/ethnicity produced under Ecuador's state-led multiculturalism. Using national-scale cartography as a means to examine contested processes of rearticulating state, citizen and nation, the paper analyses recent transformations in cartography, nation building and geographical knowledge in Ecuador. Directing a critical analysis towards the ways maps of indigenous populations are produced, circulated, authorised and read provides a distinctive lens by which to explore postcolonial questions of belonging, rights and presence. The paper discusses how, despite the emergence of innovative maps, the plurinational project envisaged by indigenous cartographers remains stymied by a series of material, cultural and postcolonial limitations.
A DETERMINANT FORMULA FOR RELATIVE CONGRUENCE ZETA FUNCTIONS FOR CYCLOTOMIC FUNCTION FIELDS
Authors: SHIOMI DAISUKE
Published: July 2010

Rosen gave a determinant formula for relative class numbers for cyclotomic function fields, which may be regarded as an analogue of the classical Maillet determinant. In this paper, we give a determinant formula for relative congruence zeta functions for cyclotomic function fields. Our formula may be regarded as a generalization of the determinant formula for the relative class number.
Inherent Vice: Minsky, Markomata, and the tendency of markets to undermine themselves
Authors: MIROWSKI PHILIP
Published: July 2010

Most current explanations of the crisis which began in 2007/8 tend to search for scapegoats, in the format of behavioral flaws. Their treatment of ‘risk’ is an important signpost to where such theories go awry. This paper suggests a structural theory of the crisis, informed by Institutionalist themes. We insist there is an alternative to a neoclassical macroeconomics, in the guise of possible alternative heterodox microfoundations for Minsky's account of economic crises, beyond the Kaleckian markup model. The sketch is based upon elevation of some formal notions of computational complexity to pride of place, and characterization of crises as a collapse of complexity. It is an attempt to portray a market system evolving to a point of ‘inherent vice’: an endogenous development which by its very nature, cannot be tamed through conventional insurance or risk models.
How does opportunistic behavior influence firm size? An evolutionary approach to organizational behavior
Authors: CORDES CHRISTIAN , RICHERSON PETER , MCELREATH RICHARD , STRIMLING PONTUS
Published: July 2010

This paper relates firm size and opportunism by showing that, given certain behavioural dispositions of humans, the size of a profit-maximizing firm can be determined by cognitive aspects underlying firm-internal cultural transmission processes. We argue that what firms do better than markets – besides economizing on transaction costs – is to establish a cooperative regime among its employees that keeps in check opportunism. A model depicts the outstanding role of the entrepreneur or business leader in firm-internal socialization processes and the evolution of corporate cultures. We show that high opportunism-related costs are a reason for keeping firms’ size small.
Factorial Invariance of Child Self-Report Across English and Spanish Language Groups in a Hispanic Population Utilizing the PedsQL™ 4.0 Generic Core Scales
Authors: Newman Daniel A. , Limbers Christine A. , Varni James W.
Published: July 2010

The measurement of health-related quality of life (HRQOL) in children has witnessed significant international growth over the past decade in an effort to improve pediatric health and well-being, and to determine the value of health-care services. In order to compare international HRQOL research findings across language groups, it is important to demonstrate factorial invariance, i.e., that the items have an equivalent meaning across the language groups studied. This study examined the factorial invariance of child self-reported HRQOL across English- and Spanish-language groups in a Hispanic population of 2,899 children ages 8–18 utilizing the 23-item PedsQL™ 4.0 Generic Core Scales. Multigroup confirmatory factor analysis (CFA) was performed specifying a five-factor model across language groups. The findings support an equivalent 5-factor structure across English- and Spanish-language groups. Based on these data, it can be concluded that children across the two languages studied interpreted the instrument in a similar manner. The multigroup CFA statistical methods utilized in the present study have important implications for cross-cultural assessment research in children in which different language groups are compared.
Precursor activation and substorm expansion associated with observations of a dipolarization front by Time History of Events and Macroscale Interactions during Substorms (THEMIS)
Authors: Tang C. L. , Angelopoulos V. , Runov A. , Russell C. T. , Frey H. , Glassmeier K. H. , Fornacon K. H. , Li Z. Y.
Published: July 2010

We analyzed simultaneous Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes and ground‐based observations during a set of successive auroral activations between 0600 and 0900 UT on 27 February 2009. The first (minor) activation, interpreted as a pseudobreakup, may be related to transient reconnection on closed plasma sheet field lines. During the pseudobreakup, a plasmoid was observed in the midtail. Other minor auroral activations were associated with earthward flow bursts accompanied by magnetic field disturbance in the near‐Earth plasma sheet. The effects of these minor activations (auroral brightening and ground responses) were limited in spatial scale, and weak or local variations in the near‐Earth magnetotail were observed. The slow but continuous increase in total lobe pressure suggests continuous flux accumulation in the magnetotail. A new reconnection episode likely occurred in the magnetotail, as evidenced by fast earthward flows (600∼800 km/s) accompanied by Bz > 0 observed by P1 and P2 at ∼0738 UT. At substorm expansion, an abrupt reduction in the lobe field at P5 (which had been increasing continuously) was observed. The rapid lobe flux reduction may indicate magnetotail lobe magnetic reconnection (TLR) and evolution of the expansion phase. Substorm expansion onset, as evidenced by a global expansion of auroral intensification and strong ground Pi2 pulsations, was accompanied by a decrease in total pressure and significant dipolarization and electron injections in the near‐Earth magnetotail. We interpret these minor activations (including a pseudobreakup and other minor activations at ∼0657 and ∼0705 UT) as precursors of a substorm onset. In this scenario, closed field line reconnection results in ionospheric effects consistent with very localized auroral intensifications, including limited poleward expansion. TLR provides most of the flux and energy required for fully developed substorms.
Predicting tropical cyclogenesis with a global mesoscale model: Hierarchical multiscale interactions during the formation of tropical cyclone Nargis (2008)
Authors: Shen B.‐W. , Tao W.‐K. , Lau W. K. , Atlas R.
Published: July 2010

Very severe cyclonic storm Nargis devastated Burma (Myanmar) in May 2008, caused tremendous damage and numerous fatalities, and became one of the 10 deadliest tropical cyclones (TCs) of all time. To increase the warning time in order to save lives and reduce economic damage, it is important to extend the lead time in the prediction of TCs like Nargis. As recent advances in high‐resolution global models and supercomputing technology have shown the potential for improving TC track and intensity forecasts, the ability of a global mesoscale model to predict TC genesis in the Indian Ocean is examined in this study with the aim of improving simulations of TC climate. High‐resolution global simulations with real data show that the initial formation and intensity variations of TC Nargis can be realistically predicted up to 5 days in advance. Preliminary analysis suggests that improved representations of the following environmental conditions and their hierarchical multiscale interactions were the key to achieving this lead time: (1) a westerly wind burst and equatorial trough, (2) an enhanced monsoon circulation with a zero wind shear line, (3) good upper‐level outflow with anti‐cyclonic wind shear between 200 and 850 hPa, and (4) low‐level moisture convergence.
Evaluation of satellite‐based upper troposphere cloud top height retrievals in multilayer cloud conditions during TC4
Authors: Chang Fu‐Lung , Minnis Patrick , Ayers J. Kirk , McGill Matthew J. , Palikonda Rabindra , Spangenberg Douglas A. , Smith William L. , Yost Christopher R.
Published: July 2010

Upper troposphere cloud top heights (CTHs), restricted to cloud top pressures (CTPs) < 500 hPa, inferred using four satellite retrieval methods applied to Twelfth Geostationary Operational Environmental Satellite (GOES‐12) data are evaluated using measurements during the July–August 2007 Tropical Composition, Cloud and Climate Coupling Experiment (TC4). The four methods are the single‐layer CO2‐absorption technique (SCO2AT), a modified CO2‐absorption technique (MCO2AT) developed for improving both single‐layered and multilayered cloud retrievals, a standard version of the Visible Infrared Solar‐infrared Split‐window Technique (old VISST), and a new version of VISST (new VISST) recently developed to improve cloud property retrievals. They are evaluated by comparing with ER‐2 aircraft‐based Cloud Physics Lidar (CPL) data taken during 9 days having extensive upper troposphere cirrus, anvil, and convective clouds. Compared to the 89% coverage by upper tropospheric clouds detected by the CPL, the SCO2AT, MCO2AT, old VISST, and new VISST retrieved CTPs < 500 hPa in 76, 76, 69, and 74% of the matched pixels, respectively. Most of the differences are due to subvisible and optically thin cirrus clouds occurring near the tropopause that were detected only by the CPL. The mean upper tropospheric CTHs for the 9 days are 14.2 (±2.1) km from the CPL and 10.7 (±2.1), 12.1 (±1.6), 9.7 (±2.9), and 11.4 (±2.8) km from the SCO2AT, MCO2AT, old VISST, and new VISST, respectively. Compared to the CPL, the MCO2AT CTHs had the smallest mean biases for semitransparent high clouds in both single‐layered and multilayered situations whereas the new VISST CTHs had the smallest mean biases when upper clouds were opaque and optically thick. The biases for all techniques increased with increasing numbers of cloud layers. The transparency of the upper layer clouds tends to increase with the numbers of cloud layers.
Study of impact demagnetization at Mars using Monte Carlo modeling and multiple altitude data
Authors: Lillis Robert J. , Purucker Michael E. , Halekas Jasper S. , Louzada Karin L. , Stewart‐Mukhopadhyay Sarah T. , Manga Michael , Frey Herbert V.
Published: July 2010

The magnetic field signatures of large demagnetized impact basins on Mars offer a unique opportunity to study the magnetic properties of the crust and the processes of basin formation and impact shock demagnetization. We present a framework for determining the effects on such signatures due to the dominant direction, strength, thickness, and vertical and horizontal coherence wavelengths of the surrounding crustal magnetization, as well as the demagnetization radius and the width of the demagnetization gradient zone caused by impact shock. By comparing model results with observed magnetic field profiles at 185 km and 400 km over the five largest apparently demagnetized impact structures, we find that (1) the dominant lateral size of coherently magnetized regions of crust falls in the range ∼325 km to 600 km, (2) the magnetic field observed over a circular demagnetized region is such that clear demagnetization signatures should only be visible in magnetic field maps at 185 km and 400 km altitude for demagnetization diameters larger than ∼600 km and ∼1000 km, respectively, (3) demagnetization radii can be meaningfully constrained despite relatively poor constraints on associated demagnetization gradient zone widths, (4) the ratio of demagnetization diameter to the outer topographic ring diameter is close to 0.8 for the Isidis, Hellas, Argyre, and Utopia basins, suggesting that similar basin‐forming and shock demagnetization processes occurred in each of these four ancient impacts, and (5) if used in conjunction with impact simulations, such modeling may lead to improved constraints on peak pressure contours and impact energies for these basins.
Modeling particle transport in downward and upward flows
Authors: Basha H. A. , Culligan P. J.
Published: July 2010

Experimental data obtained for particle transport in downward and upward flows in smooth and rough porous media are analyzed at various flow rates. The data analysis and interpretation are aided through an analytical model with linear kinetics that assumes two sites for particle deposition within a medium, namely, reversible and irreversible, together with a dual mode of irreversible deposition. The bimodal particle transport model is obtained using the Green's function method and is capable of fitting, with reasonable accuracy, the observed transport and deposition behavior of particles. Approximations for advection‐dominated flows are also obtained that could represent a simplified modeling tool. Expressions of the temporal moments are developed and algebraic equations are derived that express the model parameters in terms of the moments of the measured particle concentration distributions. The transport models helped define the relationship of the modeled parameters to flow velocity and media roughness. The fitting results show that the parameters for rough and smooth media vary in a systematic way with the pore fluid velocity. The results also reveal that flow direction has a significant influence on the mode and magnitude of irreversible particle deposition for the conditions investigated. For the same seepage velocity, the rate of particle deposition is greater for upward flows than for downward flows. Moreover, roughness effects increase the irreversible particle deposition in downward flows but have little effect in upward flows.
Permeability estimates of self‐affine fracture faults based on generalization of the bottleneck concept
Authors: Talon L. , Auradou H. , Hansen A.
Published: July 2010

We propose a method for calculating the effective permeability of two‐dimensional self‐affine permeability fields based on generalizing the one‐dimensional concept of a bottleneck. We test the method on fracture faults where the local permeability field is given by the cube of the aperture field. The method remains accurate even when there is substantial mechanical overlap between the two fracture surfaces. The computational efficiency of the method is comparable to calculating a simple average and is more than two orders of magnitude faster than solving the Reynolds equations using a finite difference scheme.
Protein catabolism and impairment of skeletal muscle insulin signalling in heart failure
Authors: Schulze P. Christian
Published: July 2010

Derangements in systemic and local metabolism develop in patients with CHF [chronic HF (heart failure)] and contribute to the progression of the disease. Impaired skeletal muscle metabolism, morphology and function leading to exercise intolerance are hallmarks of the syndrome of CHF. These changes result in abnormal glucose and lipid metabolism, and the associated insulin resistance, which contribute to progression of skeletal muscle catabolism and development of muscle atrophy in patients with advanced HF. In the present issue of Clinical Science, Toth and co-workers demonstrate the impairment of skeletal muscle protein metabolism in patients with HF, and specifically show an impaired anabolic response in the skeletal muscle of these patients following a period of nutritional deficiency.
Sensitivity to local anaesthetics among asthmatic children
Authors: Çetinkaya F.
Published: July 2010

Objectives.

Although true allergic reactions to local anaesthetics are rare in the general population, the importance of the problem among asthmatic children has yet to be documented.

Sample and methods.

Skin prick, intradermal and incremental challenge tests with lidocain were performed in 157 asthmatic children aged 8–15 years and compared with 72 nonasthmatic children of a similar age. All of the asthmatic subjects were allergic to at least one allergen, most frequently pollens and house dust mites. Prick testing began with an undiluted solution in patients without a history of allergy and with 1:100 dilution in those with a reaction history. Following negative prick testing, intradermal or incremental challenge tests were performed.

Results.

A total of 125 patients (80%) had been given local anaesthetics in the past, only three children gave history of an adverse local reaction. At the end of the tests, none of the subjects including controls, were found to have immediate or delayed‐type allergy to lidocain.

Conclusions.

Local anaesthetic allergy does not seem to be a serious problem among asthmatic children and testing in all asthmatic children is not warranted. Those with an adverse reaction history to local anaesthetics should be tested with these drugs.
The relationship between erosion, caries and rampant caries and dietary habits in preschool children in Saudi Arabia
Authors: Al‐Malik M. I. , Holt R. D. , Bedi R.
Published: July 2010

Objectives.

The aim of this study was to investigate the possible association between dental erosion and caries, and variables including socio‐economic status, reported dietary practices and oral hygiene behaviour, in a sample of children in Jeddah, Saudi Arabia. A cross‐sectional study including dental examination and questionnaire survey was carried out at a number of kindergartens.

Sample and methods.

A sample of 987 children (2–5‐year‐olds) was drawn from 17 kindergartens. Clinical examinations were carried out under standardized conditions by a trained and calibrated examiner (MAM). Information regarding diet and socio‐economic factors was drawn from questionnaires distributed to the parents through the schools. These were completed before the dental examination.

Results.

Of the 987 children, 309 (31%) showed signs of erosion. Caries were diagnosed in 720 (73%) of the children and rampant caries in 336 (34%). Vitamin C supplements, frequent consumption of carbonated drinks and the drinking of fruit syrup from a feeding bottle at bed‐ or nap‐time when the child was a baby, were all related to erosion. Consumption of carbonated drinks and fruit syrups was also related to caries but they were part of a larger number of significant factors including socio‐demographic measures and oral hygiene practices.

Conclusions.

There was no clear relationship between erosion and social class, or between erosion and oral hygiene practices; the reverse was true for caries. Dietary factors relating to both erosion and caries and/or rampant caries were found in this sample of children.
Age‐Associated Changes in Hypothalamic and Pituitary Neuroendocrine Gene Expression in the Rat
Authors: Kappeler L. , Gourdji D. , Zizzari P. , Bluet‐Pajot M.‐T. , Epelbaum J.
Published: July 2010

A cDNA membrane array displaying 1183 probes was used to detect hypothalamic and pituitary changes in gene expression accompanying ageing and age‐associated pituitary macroadenomas. Four groups of male Sprague‐Dawley rats (3‐, 15‐, 24‐month‐old and 24‐month‐old with prolactinoma) were compared in two independent hybridizations. cDNA array data were confirmed and completed by comparative reverse transcriptase‐polymerase chain reaction on selected genes. The expression of 454 and 116 mRNAs was detected in hypothalamus and pituitary, respectively. Growth hormone (GH) mRNA alone represented 85% of total gene expression in the gland of young rats, and other pituitary hormone transcripts 2.8%, while melanin‐concentrating hormone (MCH) mRNA, the most expressed neuropeptide transcript involved in neuroendocrine regulation, accounted for only 0.8% of total hypothalamic transcripts. The proportion of genes modified in the hypothalamus and pituitary was rather modest: 1.5% and 5.2%, respectively, for ageing per se, and 1.1% and 5.2% for age‐associated macroprolactinomas. Among pituitary specific RNAs, GH mRNA expression was notably decreased with age. At the hypothalamic level, expression of genes directly involved in GH regulation, such as somatostatin and growth hormone‐releasing hormone, was not altered, while neuropeptide transcripts involved in feeding behaviour [orexin/hypocretin, MCH, pro‐opiomelanocortin (POMC), cocaine‐ and amphetamine‐regulated transcript (CART)] were significantly altered. In addition, a few ubiquitous transcripts (hnRNP‐K, PFKm, CCND 2, calponin and set) were differently affected in both tissues. Modifications in hypothalamic orexigenic (orexin, MCH) and anorexigenic (POMC, CART) gene expression are in keeping with an age‐associated decrease in energy consumption but a higher one in the presence of macroprolactinomas.
Sex Differences in the Developing Brain: Crossroads in the Phosphorylation of cAMP Response Element Binding Protein
Authors: Auger A. P.
Published: July 2010

Although it is widely known that steroid hormones differentiate the brain, little is known about the signal transduction pathways that are influenced by steroid hormones during development. This review focuses on divergence in the phosphorylation of cAMP response element binding protein (CREB) in the developing male and female rat brain. At birth, males have an increased phosphorylation of CREB compared to females. As CREB mediates changes in cellular morphology, function and survival rates, its activation may underlie an important event in steroid‐mediated sexual differentiation of the brain. The importance of CREB is further supported by a sex difference in the expression of the nuclear receptor coactivator, CREB‐binding protein, a critical factor involved in the genomic actions of CREB. This suggests that the developing male brain may be in a hyper‐responsive state to factors that lead to increased phosphorylation of CREB, resulting in divergent responses in males versus females. An example of this divergence is the response to GABA. In the male rat brain, GABA action leads to increased phosphorylation of CREB; whereas GABA action in the female brain leads to decreased phosphorylation of CREB. The potential consequences of this divergence in the regulation of CREB are discussed in relation to adult sexually dimorphic brain morphology, physiology and behaviour.
Diagnosis and prediction of recurrence and progression in superficial bladder cancers with DNA image cytometry and urinary cytology
Authors: Desgrippes A. , Izadifar V. , Assailly J. , Fontaine E. , Beurton D.
Published: July 2010

Objective To investigate the roles of urinary cytology and image cytometric analysis of nuclear DNA ploidy pattern in the diagnosis and prediction of recurrence and/or progression of superficial bladder cancers.

Patients and methods Aliquots of catheterized urine from 92 patients with primary (23) or previous (69) superficial bladder cancers were assessed using urine cytology and image‐analysis cytometry independently.

Results Of the 23 primary superficial transitional cell carcinomas (TCCs), 11 (48%) were detected by urinary cytology while 12 (52%) were detected by image‐analysis cytometry (P > 0.05) and 13 (57%) were revealed by combined cytology and cytometry. Of 42 recurrent superficial TCCs, 29 (69%) were detected by urinary cytology, whilst 19 (45%) were diagnosed by cytometry (P < 0.05) and 29 (69%) by combined cytology and cytometry. The degree of ploidy in relation to pathological stage and/or grade showed an increasing frequency of aneuploid pattern in more invasive and undifferentiated tumours, but with no statistical significance (P > 0.05). The positivity of DNA image cytometry had no significant association (P > 0.05) with tumour recurrence and/or progression.

Conclusions DNA image cytometry can provide a limited but not significant advantage over urinary cytology in the detection of primary superficial TCCs, but it does not seem to be indicated for the prediction of tumour recurrence and/or progression.
Urological complications after living‐donor renal transplantation
Authors: El‐Mekresh M. , Osman Y. , Ali‐El‐Dein B. , El‐Diasty T. , Ghoneim M.A.
Published: July 2010

ObjectiveTo determine the incidence and management of urological complications after 1200 consecutive live‐donor renal transplantations, all of which were carried out in one centre; the possible risk factors and the effect on patient and graft survival were also assessed.

Patients and methodsData were retrieved from an electronic database; the incidence of urological complications was determined, and correlated with relevant risk factors by univariate and multivariate analysis. The effect on patient and graft survival was assessed using Kaplan–Meier statistics.

ResultsThere were 100 complications in 96 patients (8%); urinary leaks occurred in 37, ureteric strictures in 23 and lymphoceles causing ureteric obstruction in 17. Percutaneous needle biopsy was complicated by haematuria and clot anuria in six patients. Late complications included 11 cases of stones, four of bladder malignancy and two of haemorrhagic cystitis. There was evidence that the age of the recipients (< 10 years), method of establishing urinary continuity (uretero‐ureteric anastomosis) and a high dose of steroids had an independent positive effect on the incidence of urological complications. However, their development did not influence graft or patient survival.

ConclusionWhen there is meticulous attention to the technical details, renal transplantation should incur few urological complications. Early intervention with percutaneous drainage reduces morbidity and the likelihood loss of graft function. Proper and prompt management should not affect the graft and/or the patient's survival.
Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c‐fos and junB in PC12 Cells
Authors: Haby Christelle , Lisovoski Fabrice , Aunis Dominique , Zwiller Jean
Published: July 2010

Abstract: Stimulation of several second messenger pathways induces the expression of immediate early genes such as c‐fos, c‐jun, junB, and junD, but little is known about their induction via the stimulation of the cyclic GMP pathway. Here we looked at the expression of early genes in pheochromocytoma PC12 cells after activation of cytosolic guanylate cyclase by sodium nitroprusside. This compound spontaneously releases NO, a molecule known to be involved in cell communication. We found that expression of c‐fos and junB but not of c‐jun or junD is increased upon activation of cyclic GMP pathway. c‐fos mRNA expression was the most activated (fourfold at 30 min), whereas junB response was more modest (2.2‐fold activation at 60 min). Nuclear extracts of stimulated cells show increased binding capacity to the AP1 binding site consistent with the dose‐response curve. The activating effect of nitroprusside could be reproduced by dipyridamole, a selective cyclic GMP phosphodiesterase inhibitor and by 8‐p‐chlorophenylthio‐cyclic GMP, a permeant selective cyclic GMP‐dependent protein kinase activator, and abolished by KT5823, an inhibitor of that kinase. The results show that NO promotes early gene activation and AP1 binding enhancement through the stimulation of the cyclic GMP pathway.
Heterogeneity of Nucleotide Receptors in NG108‐15 Neuroblastoma and C6 Glioma Cells for Mediating Phosphoinositide Turnover
Authors: Lin Wan‐Wan
Published: July 2010

Abstract: We have compared the characteristics of receptors for nucleotide analogues and the involvement of phospholipase C (PLC) in the effector mechanism in NG108‐15 neuroblastoma and C6 glioma cells. The relative potency of these analogues to stimulate inositol phosphate (IP) formation is UTP > UDP ≫ 2‐methylthio‐ATP (2‐MeSATP), GTP > ATP, CTP > ADP > UMP in NG108‐15 cells and ATP > UTP > ADP > GTP > UDP ≫ 2Me‐SATP, CTP, UMP in C6 glioma cells. α,β‐Methylene‐ATP, β,γ‐methylene‐ATP, AMP, and adenosine had little or no effect in both types of cells. The EC50 values were 3 and 106 µM for UTP in NG108‐15 and C6 glioma cells, respectively. The EC50 value for ATP in C6 glioma cells was 43 µM. 2‐MeSATP was threefold more potent than ATP in NG108‐15 cells but had little effect in C6 glioma cells at 1 mM. In NCB‐20 cells, a similar rank order of potency to that found in NG108‐15 cells, i.e., UTP ≫ GTP > ATP > CTP, was observed. In both NG108‐15 and C6 glioma cells, preincubation with ATP or UTP caused a pronounced cross‐desensitization of subsequent nucleotide‐stimulated IP production. ATP and UTP displayed no additivity in terms of IP formation at maximally effective concentrations. In contrast, endothelin‐1, bradykinin, and NaF interacted in an additive manner with either nucleotide in stimulating PI hydrolysis. Pretreatment with pertussis toxin did not affect ATP‐, UTP‐, and GTP‐stimulated IP generation in these cells, indicating that nucleotide receptors coupled to PLC by a pertussis toxin‐resistant G protein in both cell types. Short‐term treatment of the cells with protein kinase C (PKC) activators [phorbol 12‐myristate 13‐acetate (PMA) and octylindolactam V] produced a dose‐dependent inhibition of ATP‐ and UTP‐induced IP formation with a greater extent and higher susceptibility in C6 glioma cells than in NG108‐15 cells. Furthermore, a 24‐h exposure of the cells to PMA resulted in an obvious attenuation of nucleotide‐induced IP formation in C6 glioma cells but failed to change the response in NG108‐15 cells. These results suggest that distinct nucleotide receptors that respond to ATP and UTP with different selectivity exist in NG108‐15 and C6 glioma cells. These heterogeneous nucleotide receptors coupled to PLC undergo discriminative modulation by PKC. NG108‐15 and NCB‐20 neuroblastoma are two cell lines that showed the highest specificity to extracellular UTP rather than ATP among the nucleotide receptors so far studied in various cells, suggesting the presence of a pyrimidine receptor in these cells.
Relevance of Endogenous Ascorbate and Tocopherol for Brain Cell Vitality Indicated by Photon Emission
Authors: Reiber H. , Martens U. , Prall F. , Uhr M.
Published: July 2010

Abstract: In vitro lipid peroxidation of brain cell membranes was recorded directly by monitoring the concomitant photon emission. Chemiluminescence appeared spontaneously after disintegration of vital brain cells (pig brain cell homogenate, isolated oligodendrocytes), decreasing the high intracellular ascorbate concentration in the vital glial cell (1 mmol/L) to a lower overall concentration (<100 µmol/L). This had a prooxidant effect in the homogenate. Intracellular high antioxidant ascorbate concentrations were also efficient at protecting membrane lipids of vital oligodendrocytes against extracellular low prooxidant ascorbate concentrations (50 µmol/L). The intramembranous α‐tocopherol content limited the antioxidant efficiency of ascorbate. With physiological concentrations (0.4 nmol of iron to 0.1 nmol of tocopherol per milliliter of membrane suspension), a 50% inhibition of lipid peroxidation was obtained with 410 nmol/ml ascorbate; this was reduced to 90 nmol/ml in the case of fivefold increased tocopherol content. So in vivo ascorbate concentrations were sufficient to protect against lipid peroxidation. Only when endogenous tocopherol was decreased to 20% was the in vivo intracellular ascorbate concentration too small for antioxidative protection of lipids. The product of tocopherol concentration and ascorbate concentration, effective for 50% inhibition of lipid peroxidation, remained constant. When iron concentrations were increased 104‐fold, maximal chemiluminescence and malondialdehyde formation were increased twofold and less than 50%, respectively. This quantitative description of the interactions between vitamin E, vitamin C, and iron are relevant to the modification of interpretations of pathological conditions in parkinsonian brains. The chemiluminescent indicator reaction was characterized as a separate step following lipid peroxidation and malondialdehyde formation. Its relevance as a new tool for sensitive monitoring of changing cell vitality, e.g., by virus infection of cells or by endogenous metabolites, is discussed.
α, βI, βII, δ, and ε Protein Kinase C Isoforms and Compound Activity in the Sciatic Nerve of Normal and Diabetic Rats
Authors: Borghini Isabelle , Ania‐Lahuerta Aldonza , Regazzi Romano , Ferrari Giovanna , Gjinovci Asllan , Wollheim Claes B. , Pralong William‐F.
Published: July 2010

Abstract: Defective protein kinase C (PKC) has been implicated in impaired Na+,K+‐ATPase activity in the sciatic nerve of streptozotocin‐induced diabetic rats. In the present study, α, βI, βII, γ, δ, and ε isoform‐specific antibodies were used in parallel to the measurement of compound PKC activity for the characterization of PKC distribution and isoform expression in sciatic nerves of normal and diabetic rats. To distinguish isoform expression between the axonal and glial compartments, PKC isoforms were evaluated in nerves subjected to Wallerian degeneration and in a pure primary Schwann cell culture. α, βI, βII, δ, and ε but no γ isoforms were detected in sciatic nerve. Similar immunoreactivity was observed in degenerated nerves 3–4 days after transection except for diminished βI and ε species; in Schwann cell cultures, only α, βII, δ, and ε were detected. In normal nerves, two‐thirds of PKC compound activity was found in the cytosol and 50% of total enzyme activity translocated to the Na+,K+‐ATPase‐enriched membrane fraction with phorbol myristate acetate. Similar redistribution patterns were observed for the immunoreactivity of all isoforms with the exception of δ, which did not translocate to the membrane with phorbol myristate acetate. No abnormality in compound PKC activity, in the immunoreactive intensity, or in the distribution of PKC isoforms could be detected in rat sciatic nerve after 6–12 weeks of diabetes. Thus, defective activation rather than decreased intrinsic PKC activity may occur in diabetic neuropathy.
Alzheimer's Disease Abnormally Phosphorylated τ Is Dephosphorylated by Protein Phosphatase‐2B (Calcineurin)
Authors: Gong Cheng‐Xin , Singh Toolsee J. , Grundke‐Iqbal Inge , Iqbal Khalid
Published: July 2010

Abstract: Abnormally hyperphosphorylated τ is the major protein subunit of paired helical filaments in Alzheimer brains. We have examined its site‐specific dephosphorylation by different protein phosphatases. Dephosphorylation of τ was monitored by its interaction with several phosphorylation‐dependent antibodies. Alzheimer τ was dephosphorylated by brain protein phosphatase‐2B at the abnormally phosphorylated sites Ser46, Ser199, Ser202, Ser235, Ser396, and Ser404, and its relative mobility on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis shifted to that of normal τ. Protein phosphatases‐1 and ‐2A could dephosphorylate only some of the above six phosphorylation sites. These results indicate that protein phosphatase‐2B might be involved in hyperphosphorylation of τ in Alzheimer's disease.
Nicotine Tolerance in Chromaffin Cell Cultures: Acute and Chronic Exposure to Smoking‐Related Nicotine Doses
Authors: Bullock Amy E. , Barke Kim E. , Schneider Allan S.
Published: July 2010

Abstract:Nicotine tolerance and dependence are key aspects of tobacco addiction; however, the cellular mechanisms underlying these phenomena are poorly understood. Adrenal chromaffin cells release catecholamines upon exposure to nicotine and with repeated exposure this response exhibits nicotine tolerance. Using bovine adrenal chromaffin cells in culture, we have demonstrated acute and chronic nicotine tolerance at doses relevant to that in the blood and tissues of smokers (10–7Mto 10–6M). Chromaffin cells are preexposed to low doses of nicotine for time periods ranging from 10 min to 7 days and then subsequently challenged with a maximally stimulating dose of nicotine (10–5M) for 10 min, all at 37°C. Preexposure to nicotine results in a depression of45Ca uptake and catecholamine release upon subsequent nicotine challenge. Acute tolerance or desensitization of nicotinestimulated catecholamine release begins to occur in minutes after preexposure to 10–6Mnicotine at 37°C. The depression of catecholamine release upon preexposure to nicotine is both dose and temperature dependent and is not seen with potassium‐evoked release. Chronic exposure to 10–7Mnicotine for 3 days led to a depression of the secretory response to ∼70% of control responses. There was a trend toward recovery of full response by days 5 and 7 of 10–7Mnicotine preexposure. Nearly complete depression of the nicotine‐evoked release occurs within the first day of exposure to 10–6Mnicotine and persists for at least a week of nicotine exposure at 37°C. Nicotine tolerance in the catecholamine release response was reversible after nicotine washout. Cross‐tolerance between nicotine, acetylcholine, and dimethylphenylpiperazinium was observed after 5 days’exposure to one agonist and subsequent challenge with a different agonist. Acute tolerance is likely to be related to nicotinic receptor desensitization. The mechanisms of chronic tolerance and potential adaptive cellular changes remain to be determined.
Pentylenetetrazole‐Induced Chemoshock Affects Protein Kinase C and Substrate Proteins in Mouse Brain
Authors: Chen Ching‐Chow
Published: July 2010

Abstract: Protein kinase C (PKC) activity, western blot analysis of PKCα, β, γ, ε, and ζ by isozyme‐specific antibodies, and in vitro phosphorylation of endogenous substrate proteins were studied in the mice brain after pentyl‐enetetrazole‐induced chemoshock. The PKC isozymes and endogenous substrates in the crude cytosolic and membrane fractions were partially purified by DE‐52 columns eluted with buffer A containing 100 or 200 mM KCI. This method consistently separates cytosolic and membrane proteins and various PKC isoforms. The 100 mM KCI eluates from DE‐52 columns contain more PKC α and β in both cytosol and membrane than the 200 mM KCI eluates, whereas PKCγ, ε, and ζappear in equal amounts in these two eluates. The kinase activity assayed by phosphorylation of exogenous histone was increased in the chemoshocked mice in both the cytosol and membrane of 200 mM KCI eluates. In further analysis by immunoblotting, this increased activity was found to be due to the increase in content of PKC7 isozyme. As for novel‐type ε and ζ isozymes, they were not altered in the chemoshocked mice. From autoradiography, the endogenous substrate 17‐kDa neurogranin, which was shown below 21 kDa, was mostly eluted by 100 mM KCI from the DE‐52 column, whereas 43‐kDa neuromodulin, which was also demonstrated in sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis, only appeared in the 200 mM KCI eluates. The in vitro phosphorylation of neuromodulin was found to be increased in the chemoshocked mice. Therefore, the increased phosphorylation of neuromodulin and increased content of the PKCγ isoform were involved in the pentylenetetrazole‐induced chemoshock.
Inhibition of Glutamate Dehydrogenase in Brain Mitochondria and Synaptosomes by Mg2+ and Polyamines: A Possible Cause for Its Low In Vivo Activity
Authors: Kuo Nina , Michalik Mariusz , Erecińska Maria
Published: July 2010

Abstract: Magnesium and the polyamines putrescine, spermidine, and spermine inhibited the activity of glutamate dehydrogenase in permeabilized rat brain mitochondria in a concentration‐dependent manner. The inhibitory effect was observed on both the reductive amination of 2‐oxoglutarate and oxidative deamination of glutamate, as well as in the presence and absence of ADP and leucine, the allosteric activators of the enzyme. Kinetic studies at various concentrations of substrates showed that inhibition by magnesium and spermine was very pronounced at 2‐oxoglutarate concentrations less than 0.5 mM and NADH levels less than 0.08 mM. The presence of the former compounds also accentuated the inhibitory effect of high concentrations of 2‐oxoglutarate (>2.0 mM) and NADH (>0.32 mM). Addition of magnesium and spermine to suspensions of synaptosomes decreased the amount of ammonia produced from glutamate. It is suggested that polyamines and magnesium, normal constituents of mammalian brain, are responsible, at least in part, for the low glutamate dehydrogenase activity in vivo.
SV2 and o‐rab3 Remain Associated with Recycling Synaptic Vesicles
Authors: Wittich Beate , Volknandt Walter , Zimmermann Herbert
Published: July 2010

Abstract: o‐rab3 is an electric ray homologue of low molecular weight GTP‐binding proteins thought to be involved in targeting of secretory vesicles to sites of exocytosis. The stimulation‐dependent association of o‐rab3 with synaptic vesicles was compared with that of the membrane‐integral synaptic vesicle protein 2 (SV2). On application of immunoelectron microscopy and the colloidal gold technique, antibodies against either protein labeled the synaptic vesicle membrane compartment. Synaptic vesicles recycled under conditions of low frequency stimulation (0.1 Hz) retained their complement of both SV2 and o‐rab3. Isolation of synaptic vesicles by density‐gradient centrifugation and subsequent column chromatography yielded no indication of a stimulation‐dependent release of o‐rab3 from synaptic vesicles. In contrast, multivesicular bodies and vacuoles occasionally observed in the nerve terminals contained SV2 but little if any o‐rab3. It is concluded that o‐rab3 remains associated with the synaptic vesicle membrane compartment during stimulation‐induced cycles of repeated exo‐ and endocytosis. o‐rab3 may be lost once the vesicle enters the prelysosomal pathway.
[3H]Dizocilpine Association Kinetics Distinguish Stimulatory and Inhibitory Polyamine Sites of N‐Methyl‐d‐Aspartate Receptors
Authors: Marvizón Juan‐Carlos , Baudry Michel
Published: July 2010

Abstract: Spermine and other polyamines both stimulate and inhibit N‐methyl‐d‐aspartate receptor function, probably by interacting with two separate sites. To characterize these two actions, the effect of spermine on the binding kinetics of the channel blocker [3H]dizocilpine was studied in the presence of glutamate and glycine. Low concentrations (10 µM) of spermine increased the association and dissociation rates without modifying equilibrium binding, indicating that spermine increases the accessibility of [3H]dizocilpine to the channel by interacting with a high‐affinity, stimulatory site. At higher concentrations (1 mM), spermine markedly decreased equilibrium [3H]‐dizocilpine binding by decreasing both affinity and Bmax, indicating that spermine allosterically inhibits binding by interacting with a second, low‐affinity site. The presumed polyamine antagonists arcaine, diethylenetriamine, and 1,10‐diaminodecane completely inhibited equilibrium [3H]dizocilpine binding, probably by interacting with the inhibitory polyamine site or other sites, but not with the stimulatory polyamine site. Low concentrations (10 µM) of ifenprodil completely reversed the increase in association rate produced by spermine, whereas higher concentrations (IC50 = 123 µM) inhibited equilibrium binding, indicating that ifenprodil is both a potent antagonist of the stimulatory site and a low‐affinity ligand of the inhibitory site. The polyamine agonists spermine, spermidine, and neomycin interacted with the inhibitory site, but produced only partial inhibition of equilibrium [3H]dizocilpine binding.
Isoform Specific Reductions in Na+,K+‐ATPase Catalytic (α) Subunits in the Nerve of Rats with Streptozotocin‐Induced Diabetes
Authors: Fink David J. , Datta Subhash , Mata Marina
Published: July 2010

Abstract: Na+,K+‐ATPase activity in nerve is reduced in rats with streptozotocin‐induced diabetes; three different isoforms of the α (catalytic) subunit of the enzyme are present in nerve. Using western blot to determine subunit isoform polypeptide levels in sciatic nerve, we found a substantial reduction in α1‐isoform polypeptide (88% at 3 weeks, 94% at 8 weeks) after induction of diabetes by streptozotocin. Reductions in α2 and α3 polypeptide were smaller and not statistically significant. The reduction in amount of all three isoform polypeptides in the nerve of 3‐week diabetic animals was corrected by administration of insulin. Accumulation of α1 polypeptide at a nerve ligature indicated that rapid transport of that polypeptide in nerve occurs with normal kinetics. The results implicate a specific marked deficit in α1, much more than α2 or α3, catalytic subunit isoform of Na+,K+‐ATPase in the pathogenesis of diabetic neuropathy.