bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the relative contribution of COX‐1 and COX‐2 isoforms to ischemia‐induced oxidative damage and neurodegeneration following transient global cerebral ischemia
Authors: Candelario‐Jalil Eduardo , González‐Falcón Armando , García‐Cabrera Michel , Álvarez Dalia , Al‐Dalain Said , Martínez Gregorio , León Olga Sonia , Springer Joe E.
Published: July 2003

We investigated the relative contribution of COX‐1 and/or COX‐2 to oxidative damage, prostaglandin E2 (PGE2) production and hippocampal CA1 neuronal loss in a model of 5 min transient global cerebral ischemia in gerbils. Our results revealed a biphasic and significant increase in PGE2 levels after 2 and 24–48 h of reperfusion. The late increase in PGE2 levels (24 h) was more potently reduced by the highly selective COX‐2 inhibitor rofecoxib (20 mg/kg) relative to the COX‐1 inhibitor valeryl salicylate (20 mg/kg). The delayed rise in COX catalytic activity preceded the onset of histopathological changes in the CA1 subfield of the hippocampus. Post‐ischemia treatment with rofecoxib (starting 6 h after restoration of blood flow) significantly reduced measures of oxidative damage (glutathione depletion and lipid peroxidation) seen at 48 h after the initial ischemic episode, indicating that the late increase in COX‐2 activity is involved in the delayed occurrence of oxidative damage in the hippocampus after global ischemia. Interestingly, either selective inhibition of COX‐2 with rofecoxib or inhibition of COX‐1 with valeryl salicylate significantly increased the number of healthy neurons in the hippocampal CA1 sector even when the treatment began 6 h after ischemia. These results provide the first evidence that both COX isoforms are involved in the progression of neuronal damage following global cerebral ischemia, and have important implications for the potential therapeutic use of COX inhibitors in cerebral ischemia.
Obliteration of α‐melanocyte‐stimulating hormone derived from POMC in pituitary and brains of PC2‐deficient mice
Authors: Miller Ruthellen , Aaron Wade , Toneff Thomas , Vishnuvardhan Daesety , Beinfeld Margery C. , Hook Vivian Y. H.
Published: July 2003

Alpha‐melanocyte‐stimulating hormone (α‐MSH) is a neuropeptide expressed in pituitary and brain that is known to regulate energy balance, appetite control, and neuroimmune functions. The biosynthesis of α‐MSH requires proteolytic processing of the proopiomelanocortin (POMC) precursor. Therefore, this study investigated the in vivo role of the prohormone convertase 2 (PC2) processing enzyme for production of α‐MSH in PC2‐deficient mice. Specific detection of α‐MSH utilized radioimmunoassay (RIA) that does not crossreact with the POMC precursor, and which does not crossreact with other adrenocorticotropin hormone (ACTH) and β‐endorphin peptide products derived from POMC. α‐MSH in PC2‐deficient mice was essentially obliterated in pituitary, hypothalamus, cortex, and other brain regions (collectively), compared to wild‐type controls. These results demonstrate the critical requirement of PC2 for the production of α‐MSH. The absence of α‐MSH was accompanied by accumulation of ACTH, ACTH‐containing imtermediates, and POMC precursor. ACTH was increased in pituitary and hypothalamus of PC2‐deficient mice, evaluated by RIA and reversed‐phase high pressure liquid chromatography (RP‐HPLC). Accumulation of ACTH demonstrates its role as a PC2 substrate that can be converted for α‐MSH production. Further analyses of POMC‐derived intermediates in pituitary, conducted by denaturing western blot conditions, showed accumulation of ACTH‐containing intermediates in pituitaries of PC2‐deficient mice, which implicate participation of such intermediates as PC2 substrates. Moreover, accumulation of POMC was observed in PC2‐deficient mice by western blots with anti‐ACTH and anti‐β‐endorphin. In addition, increased β‐endorphin1−31 was observed in pituitary and hypothalamus of PC2‐deficient mice, suggesting β‐endorphin1−31 as a substrate for PC2 in these tissues. Overall, these studies demonstrated that the PC2 processing enzyme is critical for the in vivo production of α‐MSH in pituitary and brain.
Cytochrome c, released from cerebellar granule cells undergoing apoptosis or excytotoxic death, can generate protonmotive force and drive ATP synthesis in isolated mitochondria
Authors: Atlante Anna , De Bari Lidia , Bobba Antonella , Marra Ersilia , Calissano Pietro , Passarella Salvatore
Published: July 2003

In rat cerebellar granule cells, cytochrome c release takes place during glutamate toxicity and apoptosis due to deprivation of depolarising levels of potassium. We show that, as in necrosis, the released cytochrome c present in the cytosolic fraction obtained from cerebellar granule cells undergoing apoptosis can operate as a reactive oxygen species (ROS) scavenger and as a respiratory substrate. The capability of the cytosolic fraction containing cytochrome c, obtained from cerebellar granule cells undergoing either necrosis or apoptosis, to energise coupled mitochondria isolated by the same cells is also investigated. We show that, in both cases, the cytosolic fraction containing cytochrome c, added to mitochondria, can cause proton ejection, and membrane potential generation and can drive ATP synthesis and export in the extramitochondrial phase, as photometrically measured via the ATP detecting system.

Cytochrome c, separated immunologically from the cytosolic fraction of apoptotic cells when added to mitochondria, is found to cause proton ejection to generate membrane potential and to drive ATP synthesis and export in a manner not sensitive to the further addition of the cytosolic fraction depleted of cytochrome c, which failed to do this. In the light of these findings we propose that in apoptosis the released cytochrome c can contribute to provide ATP required for the cell programmed death to occur.
Repeated variable prenatal stress alters pre‐ and postsynaptic gene expression in the rat frontal pole
Authors: Kinnunen Anu K. , Koenig James I. , Bilbe Graeme
Published: July 2003

Exposure of pregnant women to stress during a critical period of fetal brain development is an environmental risk factor for developing schizophrenia in the adult offspring. We have applied a repeated variable stress paradigm to pregnant Sprague–Dawley rats during the last week of gestation coinciding with the second trimester in human brain development. Here we report our findings from a microarray analysis of the frontal pole of the prenatally stressed adult offspring and non‐stressed adult controls complemented with measurement of plasma corticosterone levels following exposure to an acute stress. The direction of change of selected genes was confirmed by real time quantitative fluorescence PCR andin situhybridization. The analysis revealed significant changes in genes associated with the NMDA receptor/postsynaptic density complex and the vesicle exocytosis machinery including NMDA receptor NR1 and NR2A subunits, densin‐180, brain enriched guanylate kinase‐associated protein, synaptosome‐associated protein of 25 kDa, synaphin/complexin and vesicle‐associated membrane protein 2/synaptobrevin 2. Interestingly, some of the changes in this animal preparation are analogous to changes observed in schizophrenic and bipolar patients. Our results suggest that application of a repeated variable prenatal stress paradigm during a critical period of fetal brain development reprograms the response of the hypothalamo–pituitary–adrenal axis to acute stress and results in gene expression changes that may have enduring effects on synaptic function in the offspring during adulthood.
NT‐4 protein is localized in neuronal cells in the brain stem as well as the dorsal root ganglion of embryonic and adult rats
Authors: Katoh‐Semba Ritsuko , Ichisaka Satoshi , Hata Yoshio , Tsumoto Tadaharu , Eguchi Kazuyo , Miyazaki Noriko , Matsuda Motoko , Takeuchi Ikuo K. , Kato Kanefusa
Published: July 2003

We have newly established a sensitive, two‐site enzyme immunoassay system for neurotrophin‐4 (NT‐4) and investigated its tissue distribution in the rat nervous system. The minimal limit of detection of the assay is 0.3 pg/0.2 mL of assay mixture. Concentrations of NT‐4 were found to be extremely low in all brain regions, irrespective of the animal age, the highest level being found in the brain stem of 40‐day‐old rats, at 0.12 ng/g wet weight. NT‐4 levels in young adult rats were significantly lower in the thalamus and higher in the olfactory bulb, neocortex, hypothalamus and brain stem than respective levels in 1‐week‐old rats. NT‐4 immunoreactivity was strong in large neurons of the red nucleus and pontine reticular nucleus as well as the locus coeruleus, and moderate in cells in the mesencephalic trigeminal nucleus and interstitial nucleus of the medial longitudinal fasciculus. In the rat embryo, stong staining of NT‐4 was detected in cells of regions corresponding to the midbrain/pons from E11.5 through E15.5. The intensity was decreased after E13.5 when the cytoplasm of cells in the medulla oblongata, fibers of the cerebellar primordium, and both cells and fibers of the dorsal root ganglion were also stained. Concentrations of NT‐4 were detected in regions including the hindbrain and the dorsal root ganglion. Immunoblotting of NT‐4‐immunoreactive proteins extracted from these two regions revealed a band corresponding to mature NT‐4 with a molecular mass of ∼14 kDa. Kainic acid and another glutamte agonist, (+/–)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid did not affect NT‐4 levels in the hippocampus. The present results show NT‐4 to be localized in very limited brain cells and fibers from the embyonic period through to the young adult, suggesting specific roles in brain functions.
A palmitoylated RING finger ubiquitin ligase and its homologue in the brain membranes
Authors: Araki Kazuaki , Kawamura Meiko , Suzuki Toshiaki , Matsuda Noriyuki , Kanbe Daiji , Ishii Kyoko , Ichikawa Tomio , Kumanishi Toshiro , Chiba Tomoki , Tanaka Keiji , Nawa Hiroyuki
Published: July 2003

Ubiquitin (Ub) ligation is implicated in active protein metabolism and subcellular trafficking and its impairment is involved in various neurologic diseases. In rat brain, we identified two novel Ub ligases, Momo and Sakura, carrying double zinc finger motif and RING finger domain. Momo expression is enriched in the brain gray matter and testis, and Sakura expression is more widely detected in the brain white matter as well as in many peripheral organs. Both proteins associate with the cell membranes of neuronal and/or glial cells. We examined their Ub ligase activity in vivo and in vitro using viral expression vectors carrying myc‐tagged Momo and Sakura. Overexpression of either Momo or Sakura in mixed cortical cultures increased total polyubiquitination levels. In vitro ubiquitination assay revealed that the combination of Momo and UbcH4 and H5c, or of Sakura and UbcH4, H5c and H6 is required for the reaction. Deletion mutagenesis suggested that the E3 Ub ligase activity of Momo and Sakura depended on their C‐terminal domains containing RING finger structure, while their N‐terminal domains influenced their membrane association. In agreement, Sakura associating with the membrane was specifically palmitoylated. Although the molecular targets of their Ub ligation remain to be identified, these findings imply a novel function of the palmitoylated E3 Ub ligase(s).
Cellular prion protein function in copper homeostasis and redox signalling at the synapse
Authors: Vassallo Neville , Herms Jochen
Published: July 2003

The fundamental physiological function of native cellular prion (PrPC) remains unknown. Herein, the most salient observations as regards prion physiology are critically evaluated. These include: (i) the role of PrPC in copper homeostasis, particularly at the pre‐synaptic membrane; (ii) involvement of PrPC in neuronal calcium disturbances; and (iii) the neuroprotective properties of PrPC in response to copper and oxidative stress. Ultimately, a tentative hypothesis of basic prion function is derived, namely that PrPC acts as a sensor for copper and/or free radical stimuli, thereby triggering intracellular calcium signals that finally translate into modulation of synaptic transmission and maintenance of neuronal integrity.
Localization of the RNA‐binding proteins Staufen1 and Staufen2 at the mammalian neuromuscular junction
Authors: Bélanger Guy , Stocksley Mark A. , Vandromme Marie , Schaeffer Laurent , Furic Luc , DesGroseillers Luc , Jasmin Bernard J.
Published: July 2003

Staufen is an RNA‐binding protein, first identified for its role in oogenesis and CNS development in Drosophila. Two mammalian homologs of Staufen have been identified and shown to bind double‐stranded RNA and tubulin, and to function in the somatodendritic transport of mRNA in neurons. Here, we examined whether Staufen proteins are expressed in skeletal muscle in relation to the neuromuscular junction. Immunofluorescence experiments revealed that Staufen1 (Stau1) and Staufen2 (Stau2) accumulate preferentially within the postsynaptic sarcoplasm of muscle fibers as well as at newly formed ectopic synapses. Western blot analyses showed that the levels of Stau1 and Stau2 are greater in slow muscles than in fast‐twitch muscles. Muscle denervation induced a significant increase in the expression of Stau1 and Stau2 in the extrasynaptic compartment of both fast and slow muscles. Consistent with these observations, we also demonstrated that expression of Stau1 and Stau2 is increased during myogenic differentiation and that treatment of myotubes with agrin and neuregulin induces a further increase in the expression of both Staufen proteins. We propose that Stau1 and Stau2 are key components of the postsynaptic apparatus in muscle, and that they contribute to the maturation and plasticity of the neuromuscular junction.
Rottlerin, an inhibitor of protein kinase Cδ (PKCδ), inhibits astrocytic glutamate transport activity and reduces GLAST immunoreactivity by a mechanism that appears to be PKCδ‐independent
Authors: Susarla Bala T. S. , Robinson Michael B.
Published: July 2003

Protein kinase C (PKC) regulates the activity and/or cell surface expression of several different neurotransmitter transporters, including subtypes of glutamate transporters. In the present study, the effects of pharmacological inhibitors of PKC were studied in primary astrocyte cultures that express the glutamate aspartate transporter (GLAST) subtype of glutamate transporter. We found that general inhibitors of PKC, bisindolylmaleimide I (Bis I), bisindolylmaleimide II (Bis II), staurosporine and an inhibitor of classical PKCs, Gö6976, had no effect on Na+‐dependent glutamate transport activity. However, rottlerin, a putative specific inhibitor of PKCδ, decreased transport activity with an IC50value (less than 10 µm) that is comparable to that reported for inhibition of PKCδ. The effect of rottlerin was very rapid (maximal effect within 5 min) and was due to a decrease in the capacity (Vmax) for transport. Rottlerin also caused a drastic loss of GLAST immunoreactivity within 5 min, suggesting that rottlerin accelerates GLAST degradation/proteolysis. Rottlerin had no effect on cell surface or total expression of the transferrin receptor, providing evidence that the effect on GLAST cannot be attributed to a non‐specific internalization/degradation of plasma membrane proteins. Down‐regulation of PKCδ with chronic phorbol ester treatment did not block rottlerin‐mediated inhibition of transport activity. These results suggest a novel mechanism for regulation of the GLAST subtype of glutamate transporter and indicate that there is a rottlerin target that is capable of controlling the levels of GLAST by controlling the rate of degradation or limited proteolysis. It appears that the target for rottlerin may not be PKCδ.
Evaluation of blood–brain barrier thiamine efflux using the in situ rat brain perfusion method
Authors: Lockman P. R. , Mumper R. J. , Allen D. D.
Published: July 2003

Thiamine is an essential, positively charged (under physiologic conditions), water‐soluble vitamin requiring transport into brain. Brain thiamine deficiency has been linked to neurodegenerative disease by subsequent impairment of thiamine‐dependent enzymes used in brain glucose/energy metabolism. In this report, we evaluate brain uptake and efflux of [3H]thiamine using the in situ rat brain perfusion technique. To confirm brain distribution was not related to blood–brain barrier endothelial cell uptake, we compared parenchymal and cell distribution of [3H]thiamine using capillary depletion. Our work supports previous literature findings suggesting blood–brain barrier thiamine uptake is via a carrier‐mediated transport mechanism, yet extends the literature by redefining the kinetics with more sensitive methodology. Significantly, [3H]thiamine brain accumulation was influenced by a considerable efflux rate. Evaluation of the efflux mechanism demonstrated increased stimulation by the presence of increased vascular thiamine. The influx transport mechanism and efflux rate were each comparable throughout brain regions despite documented differences in glucose and thiamine metabolism. The observation that [3H]thiamine blood–brain barrier influx and efflux is regionally homogenous may have significant relevance to neurodegenerative disease linked to thiamine deficiency.
Na+ stimulates binding of dopamine to the dopamine transporter in cells but not in cell‐free preparations
Authors: Chen Nianhang , Rickey Judy , Reith Maarten E. A.
Published: July 2003

Although Na+ is crucial for the function of the dopamine (DA) transporter (DAT), its role in the substrate binding step has been questioned. To address this issue, we investigated the effect of Na+ on DA binding by measuring the potency of DA in inhibiting the binding of the cocaine analogue [3H]2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT) in intact cells expressing DAT in their plasma membranes and in membranes isolated from these cells. In cells, Na+ substantially enhanced the potency of DA in inhibiting CFT binding. This effect of Na+ was independent of buffer compositions and substitutes (sucrose vs. NMDG), more pronounced at 4°C than 25°C, and correlated with its stimulatory effect on DA uptake Km. Removing extracellular Na+ had little effect on intracellular concentrations of Na+ and K+, or on membrane potential. These data suggest that extracellular Na+ most likely acts at the transporter level to enhance the binding of external DA during the transport cycle. In contrast, in cell‐free membrane preparations the Na+ stimulation was abolished without impairment of the potency of DA in inhibiting CFT binding, regardless of whether sucrose was used to maintain the buffer osmolarity. The difference in Na+ dependence for DA to inhibit CFT binding between plasma membranes of intact cells and isolated membranes raises the possibility that intracellular ion environment, alone or in combination with other cellular factors, plays a critical role in determining DA–DAT interaction and the integration of Na+ modulation in this interaction.
Regulation of noradrenergic function by inflammatory cytokines and depolarization
Authors: Li Wei , Knowlton David , Woodward William R. , Habecker Beth A.
Published: July 2003

Although the sympathetic neurons innervating the heart are exposed to the inflammatory cytokines cardiotrophin‐1 (CT‐1), interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNFα) after myocardial infarction, the effects of these cytokines on noradrenergic function are not well understood. We used cultured sympathetic neurons to investigate the effects of these cytokines on catecholamine content, the tyrosine hydroxylase co‐factor, tetrahydrobiopterin (BH4), and norepinephrine (NE) uptake. CT‐1, but not IL‐6 or TNFα, suppressed NE uptake and catecholamines in these neurons, whereas CT‐1 and, to a lesser extent, IL‐6 decreased BH4 content. CT‐1 exerted these effects by decreasing tyrosine hydroxylase, GTP cyclohydrolase (GCH) and NE transporter mRNAs, while IL‐6 lowered only GCH mRNA. The neurons innervating the heart are also activated by the central nervous system after myocardial infarction. We examined the combined effect of depolarization and cytokines on noradrenergic function. In CT‐1‐treated cells, depolarization caused a small increase in BH4 and NE uptake, and a large increase in catecholamines. These changes were accompanied by increased TH, GCH and NE transporter mRNAs. CT‐1 and depolarization regulate expression of noradrenergic properties in an opposing manner, and the combined treatment results in elevated cellular catecholamines and decreased NE uptake relative to control cells.
Hypothalamic ependymal‐glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing
Authors: García María de los Angeles , Millán Carola , Balmaceda‐Aguilera Carolina , Castro Tamara , Pastor Patricia , Montecinos Hernán , Reinicke Karin , Zúñiga Felipe , Vera Juan Carlos , Oñate Sergio A. , Nualart Francisco
Published: July 2003

The GLUT2 glucose transporter and the K‐ATP‐sensitive potassium channels have been implicated as an integral part of the glucose‐sensing mechanism in the pancreatic islet β cells. The expression of GLUT2 and K‐ATP channels in the hypothalamic region suggest that they are also involved in a sensing mechanism in this area. The hypothalamic glial cells, known as tanycytes α and β, are specialized ependymal cells that bridge the cerebrospinal fluid and the portal blood of the median eminence. We used immunocytochemistry, in situ hybridization and transport analyses to demonstrate the glucose transporters expressed in tanycytes. Confocal microscopy using specific antibodies against GLUT1 and GLUT2 indicated that both transporters are expressed in α and β tanycytes. In addition, primary cultures of mouse hypothalamic tanycytes were found to express both GLUT1 and GLUT2 transporters. Transport studies, including 2‐deoxy‐glucose and fructose uptake in the presence or absence of inhibitors, indicated that these transporters are functional in cultured tanycytes. Finally, our analyses indicated that tanycytes express the K‐ATP channel subunit Kir6.1 in vitro. As the expression of GLUT2 and K‐ATP channel is linked to glucose‐sensing mechanisms in pancreatic β cells, we postulate that tanycytes may be responsible, at least in part, for a mechanism that allows the hypothalamus to detect changes in glucose concentrations.
Epileptiform activity in hippocampal slice cultures exposed chronically to bicuculline: increased gap junctional function and expression
Authors: Samoilova Marina , Li Jianxue , Pelletier Marc R. , Wentlandt Kirsten , Adamchik Yana , Naus Christian C. , Carlen Peter L.
Published: July 2003

Chronic (18 h) exposure of cultured hippocampal slices to the type‐A GABA receptor blocker, bicuculline methiodide (BMI) 10 μm increased the levels of connexin 43 (Cx43) and connexin 32 (Cx32) mRNAs, but not connexin 26 and connexin 36, as demonstrated by RNase protection assays. The levels of Cx43 and Cx32 proteins in membrane fractions detected by western blotting were also significantly increased. Immunoblotting indicated that BMI also promoted a significant expression of the transcription protein c‐fos. The rate of fluorescence recovery after photobleaching, an index of gap junctional coupling, was also significantly increased, whereas it was blocked by the gap junctional blocker, carbenoxolone (100 μm). Extracellular recordings in CA1 stratum pyramidale, performed in BMI‐free solution, demonstrated that BMI‐exposed cultures possessed synaptic responses characteristic of epileptiform discharges: (i) significantly greater frequency of spontaneous epileptiform discharges, (ii) post‐synaptic potentials with multiple population spikes, and (iii) significantly longer duration of primary afterdischarges. Carbenoxolone (100 μm), but not its inactive analog, oleanolic acid (100 μm), reversibly inhibited spontaneous and evoked epileptiform discharges. The findings of BMI‐induced parallel increases in levels of gap junction expression and function, and the increase in epileptiform discharges, which were sensitive to gap junctional blockers, are consistent with the hypothesis that increased gap junctional communication plays an intrinsic role in the epileptogenic process.
Chronic ethanol consumption enhances internalization of α1 subunit‐containing GABAA receptors in cerebral cortex
Authors: Kumar S. , Kralic J. E. , O'Buckley T. K. , Grobin A. C. , Morrow A. L.
Published: July 2003

The molecular mechanisms that underlie ethanol dependence involve alterations in the functional properties and subunit expression of GABAA receptors. Chronic ethanol exposure decreases GABAA receptor α1 subunits and increases α4 subunit levels in cerebral cortical membranes. This study explored the effect of chronic ethanol exposure on internalization of GABAA/benzodiazepine receptors. Chronic ethanol exposure increased α1 subunit levels by 46 ± 12% and [3H]flunitrazepam binding by 35 ± 9% in the clathrin‐coated vesicle (CCV) fraction. There was a corresponding 34 ± 8% decrease in α1 peptide expression and 37 ± 6% decrease in [3H]flunitrazepam binding in the synaptic fraction. Chronic ethanol consumption also increased the α1 subunit immunoprecipitate in the cytosolic fraction (77 ± 22%), measured by western blot analysis. Moreover, co‐immunoprecipitation of both clathrin and adaptin‐α with α1 subunits was increased in the cytosolic fraction, suggesting that α1 subunit endocytosis is enhanced by chronic ethanol consumption. In contrast, α4 subunit peptide levels were not altered in the CCV fraction despite a 39 ± 13% increase in peptide levels in the synaptic fraction of cortex. Moreover, acute ethanol exposure did not alter α1 subunit peptide expression or [3H]flunitrazepam binding in the synaptic or CCV fractions. These results suggest that chronic ethanol consumption selectively increases internalization of α1 subunit‐containing GABAA receptors in cerebral cortex.
Neuropeptide Y is neuroproliferative for post‐natal hippocampal precursor cells
Authors: Howell Owain W. , Scharfman Helen E. , Herzog Herbert , Sundstrom Lars E. , Beck‐Sickinger Annette , Gray William P.
Published: July 2003

New neurones are produced in the adult hippocampus throughout life and are necessary for certain types of hippocampal learning. Little, however, is known about the control of hippocampal neurogenesis. We used primary hippocampal cultures from early post‐natal rats and neuropeptide Y Y1 receptor knockout mice as well as selective neuropeptide Y receptor antagonists and agonists to demonstrate that neuropeptide Y is proliferative for nestin‐positive, sphere‐forming hippocampal precursor cells and β‐tubulin‐positive neuroblasts and that the neuroproliferative effect of neuropeptide Y is mediated via its Y1 receptor. Immunohistochemistry confirmed Y1 receptor staining on both nestin‐positive cells and β‐tubulin‐positive cells in culture and short pulse 5‐bromo‐2‐deoxyuridine studies demonstrated that neuropeptide Y has a proliferative effect on both cell types. These studies suggest that the proliferation of hippocampal neuroblasts and precursor cells is increased by neuropeptide Y and, therefore, that hippocampal learning and memory may be modulated by neuropeptide Y‐releasing interneurones.
Promising Alliances: The Critical Feminist Theory of Nancy Fraser and Seyla Benhabib
Authors: Canaday Margot
Published: July 2003

This essay examines the work of Nancy Fraser and Seyla Benhabib, two philosophers who have demonstrated that feminist theorists can usefully draw upon both postmodernism and the critical theory tradition, with which Fraser and Benhabib are more clearly associated. I argue that each theorist claims the universal ideals and normative judgements of modernism, and the contextualism, particularity, and skepticism of postmodernism. I do this by revisiting each of their positions in the now well-known Feminist Contentions exchange, by examining the diverse ways in which they reconcile universalism and difference, and by exploring each theorist's critique of the Habermasian public sphere.
The Liminal Body: The Language of Pain and Symbolism around Sati
Authors: Lakshmi Aishwarya
Published: July 2003

Recent scholarship on sati has stressed the fact that the ‘problem’ of sati is that the problem extends far beyond and begins far before the act itself. One of the things that lies prior to and post the act is language, yet sati is an act that stands in a curious relationship to language. I will examine the relationship between the physical act of sati and the language that surrounds it: the ‘story’ prior to the act which gives the act its meaning; the act itself which stands in an ironic relationship to the story –I will argue that the act is in fact possible only because it displaces the original story, so that every act of becoming sati presents itself not as a radical act in experience, but as an ‘acting out’ of the original story. It is in this acting out of a displaced story, that the boundary between the physical act and language becomes obscured and the body doing the act begins to occupy a liminal position, as it itself begins to function as a language – a language, which in its aspect of an ‘acting out’ obscures its own act. Lastly, I will consider the implications of the symbolic language of sati for the contemporary woman.
The Power of the Ordinary Subversive in Jackie Kay's Trumpet
Authors: Hargreaves Tracy
Published: July 2003

In Jackie Kay's award-winning novel, Trumpet (1998), the main character Joss Moody, a celebrated jazz trumpet player, is discovered upon his death to be anatomically female. The essay traces both postmodern and humanist affirmations of constructions of self-hood. Situating Virginia Woolf's version of a metaphysical and escapist androgyny as one kind of aesthetic against the material politics of the transgendered subject, the essay argues that Kay's novel can be seen as part of a 20th century tradition of literature and film which satirizes, parodies and painfully exposes the discontinuities of dominant sex–gender systems. The essay ends by arguing that Kay also develops these systems by imbricating sex and gender within a series of dislocated familial, sexual and racial identities, beginning with the arrival of Joss's African father in Scotland at the beginning of the 20th century.
Did Mrs Danvers Warm Rebecca's Pearls? Significant Exchanges and the Extension of Lesbian Space and Time in Literature
Authors: Hallett Nicky
Published: July 2003

This article is concerned with the ways in which literary spaces can become sexualized by the transfer of objects between women, as well as by the ways in which bodies themselves touch. It discusses how lesbian desire changes both spatial and temporal structures, via a consideration of the use of pearl imagery. In particular, it analyses the link between sexual, class and bodily construction in two texts: Daphne du Maurier's novel Rebecca (1938) and Carol Ann Duffy's poem ‘Warming Her Pearls’ (1987). These texts encode contrasting ideas about the lesbian body, ideas that are discursively textured by the periods in which they were written and by the relative ideological resistance of their writers. While du Maurier's novel establishes a concept of spatial and temporal enclosure, Duffy's poem creates an unconfined and unstable lesbian body-text. Within this, the pearl can be seen as a subversive device, destructuring and stretching the parameters of lesbian desire.
Low-order dynamical model for low-Prandtl number fluid flow in a laterally heated cavity
Authors: Jing Cheng-Jun , Henry Daniel , Ben Hadid Hamda , Imaishi Nobuyoki
Published: July 2003

By applying proper orthogonal decomposition (method of snapshots) to low Prandtl number fluid flow in a laterally heated cavity of dimensions 4×2×1 in length×width×height, characteristic basic modes have been extracted. Using Galerkin projection of the governing equations on these basic modes, a low-dimensional dynamical model (set of ordinary differential equations) was constructed. Some results obtained from the low-order model are presented and compared with those calculated by direct numerical simulation (DNS). The factors influencing the reliability of the low-order model such as the length of the reference signal, the snapshot density, the number of modes chosen for Galerkin projection, the characteristic velocity, and the chosen expansions for velocity and temperature are discussed. It is found that the low-order model can exactly reproduce the results obtained by DNS at the design conditions (i.e., for the Grashof and Prandtl numbers at which the basic modes have been obtained). The model can also fairly well approach the DNS results in a domain around these conditions. Nevertheless, it seems that such models have to be used with care and that, in any case, they can qualitatively predict the DNS results only in a not very large range around the design conditions.
Scaling in three-dimensional and quasi-two-dimensional rotating turbulent flows
Authors: Baroud Charles N. , Plapp Brendan B. , Swinney Harry L. , She Zhen-Su
Published: July 2003

We have made velocity time series measurements (using hot film probes) and velocity field measurements (using particle image velocimetry) on turbulent flow in a rotating annulus. For low annulus rotation rates the Rossby number was of order unity and the flow was three-dimensional (3D), but at high rotation rates the Rossby number was only about 0.1, comparable to the value for oceans and the atmosphere on large length scales. The low Rossby number (quasi-geostrophic) flow was nearly two-dimensional (2D), as expected from the Taylor–Proudman theorem. For the 3D flow we found that the probability distribution function (PDF) for velocity differences along the direction of the flow, δv(d)=v(x0+d)−v(x0), was Gaussian for large separations d and non-Gaussian (with exponential tails) for small d, as has been found for nonrotating turbulent flows. However, for low Rossby number flow, the PDF was self-similar (independent of d) and non-Gaussian. The exponents characterizing the structure functions, Sp=〈(δv)p〉∼dζp were obtained by the extended self-similarity method. For 3D flow the exponents departed from p/3 with increasing p, as has been found for turbulence in nonrotating flows, while for the quasi-2D turbulent flow, the exponents increased linearly with p, as expected for a self-similar flow. We applied the β-test of the hierarchical structure model [She and Lévêque, Phys. Rev. Lett. 72, 336 (1994)] and found that β remained constant at β≃0.75 as the rotation was increased from the 3D to the 2D regime; this indicates that both the quasi-2D and 3D flows are highly intermittent. The PIV images provided another indication of the intermittency—both the quasi-2D and 3D flows had coherent vortices which could be distinguished from the background flow. We also applied the γ-test of the hierarchical structure model and found that γ increased from 0.18 for the 3D flow to 0.34 for the quasi-2D flow; the latter value is in accord with expectation for self-similar turbulence. We conclude that our rotating 3D flow is similar to nonrotating turbulent flows, while the rotating quasi-2D turbulence is different from both the 3D rotating turbulence and from nonrotating 2D turbulence studied in other experiments.
Feedback control of a flow past a cylinder via transverse motion
Authors: Li Fu , Aubry Nadine
Published: July 2003

The instability giving rise to the Karman vortex street in a flow past a circular cylinder is responsible for the occurrence of large amplitude oscillations in the lift. In this work, we seek to control the instability via active feedback control by means of transverse displacements of the solid structure. Our investigation is based on Föppl’s four-dimensional potential flow model of point vortices. A feedback controller capable of manipulating the flow in order to maintain zero lift at all times is derived analytically by using perturbation methods and asymptotic expansions. We then apply the controller to the viscous flow by direct numerical simulation of the flow based on the two-dimensional Navier–Stokes equations and show that our control algorithm is capable of keeping the lift close to zero in the impulsively started viscous flow and, therefore, controlling vortex shedding. Computations are carried out at the Reynolds numbers Re=100 and Re=200.
Coherent vortices and kinetic energy ribbons in asymptotic, quasi two-dimensional f-plane turbulence
Authors: Arbic Brian K. , Flierl Glenn R.
Published: July 2003

This paper examines coherent vortices and spatial distributions of energy density in asymptotic states of numerically simulated, horizontally homogeneous, doubly periodic, quasi two-dimensional f-plane turbulence. With geophysical applications in mind, the paper progresses from freely decaying two-dimensional flow to freely decaying equivalent barotropic flow, freely decaying two-layer quasi-geostrophic (QG) flow, and, finally, statistically steady two-layer QG turbulence forced by a baroclinically unstable mean flow and damped by bottom Ekman friction. It is demonstrated here that, with suitable elaborations, a two-vortex state having a sinh-like potential vorticity/streamfunction (q/ψ) scatter plot arises in all of these systems. This extends, at least qualitatively, previous work in inviscid and freely decaying two-dimensional flows to flows having stratification, forcing, and dissipation present simultaneously. Potential vorticity steps and ribbons of kinetic energy are shown to form in freely decaying equivalent barotropic flow and in the equivalent barotropic limit of baroclinically unstable flow, which occurs when Ekman damping is strong. Thus, contrary to expectations, strong friction can under some circumstances create rather than hinder the formation of sharp features. The ribbons are present, albeit less dramatically, in moderately damped baroclinically unstable turbulence, which is arguably a reasonable model for mid-ocean mesoscale eddies.
Three-dimensional linear stability analysis of lid-driven magnetohydrodynamic cavity flow
Authors: Shatrov V. , Mutschke G. , Gerbeth G.
Published: July 2003

We present numerical results of a linear three-dimensional (3D) stability analysis of a square lid-driven cavity flow under the influence of an external magnetic field which is directed parallel to the lid. The Lorentz force has a strong influence on the two-dimensional (2D) flow structure, thereby changing number, shape and strength of the eddies. The resulting 3D stability behavior is rather complex since it depends on the 2D flow structure. Although increasing magnetic fields are able to damp 3D instability, in a parameter region around Re=3100, several branches of the neutral stability curve do exist. For a fixed Reynolds number in this range, an increase of the magnetic field strength may lead to a transition from a stable flow to an oscillatory unstable one.
Protein labeling reactions in electrochemical microchannel flow: Numerical simulation and uncertainty propagation
Authors: Debusschere Bert J. , Najm Habib N. , Matta Alain , Knio Omar M. , Ghanem Roger G. , Le Maı̂tre Olivier P.
Published: July 2003

This paper presents a model for two-dimensional electrochemical microchannel flow including the propagation of uncertainty from model parameters to the simulation results. For a detailed representation of electroosmotic and pressure-driven microchannel flow, the model considers the coupled momentum, species transport, and electrostatic field equations, including variable zeta potential. The chemistry model accounts for pH-dependent protein labeling reactions as well as detailed buffer electrochemistry in a mixed finite-rate/equilibrium formulation. Uncertainty from the model parameters and boundary conditions is propagated to the model predictions using a pseudo-spectral stochastic formulation with polynomial chaos (PC) representations for parameters and field quantities. Using a Galerkin approach, the governing equations are reformulated into equations for the coefficients in the PC expansion. The implementation of the physical model with the stochastic uncertainty propagation is applied to protein-labeling in a homogeneous buffer, as well as in two-dimensional electrochemical microchannel flow. The results for the two-dimensional channel show strong distortion of sample profiles due to ion movement and consequent buffer disturbances. The uncertainty in these results is dominated by the uncertainty in the applied voltage across the channel.
The temporally filtered Navier–Stokes equations: Properties of the residual stress
Authors: Pruett C. D. , Gatski T. B. , Grosch C. E. , Thacker W. D.
Published: July 2003

Recent interest in the development of a unifying framework among direct numerical simulations, large-eddy simulations, and statistically averaged formulations of the Navier–Stokes equations, provides the motivation for the present paper. Toward that goal, the properties of the residual (subgrid-scale) stress of the temporally filtered Navier–Stokes equations are carefully examined. This includes the frame-invariance properties of the filtered equations and the resulting residual stress. Causal time-domain filters, parametrized by a temporal filter width 0<Δ<∞, are considered. For several reasons, the differential forms of such filters are preferred to their corresponding integral forms; among these, storage requirements for differential forms are typically much less than for integral forms and, for some filters, are independent of Δ. The behavior of the residual stress in the limits of both vanishing and infinite filter widths is examined. It is shown analytically that, in the limit Δ→0, the residual stress vanishes, in which case the Navier–Stokes equations are recovered from the temporally filtered equations. Alternately, in the limit Δ→∞, the residual stress is equivalent to the long-time averaged stress, and the Reynolds-averaged Navier–Stokes equations are recovered from the temporally filtered equations. The predicted behavior at the asymptotic limits of filter width is further validated by numerical simulations of the temporally filtered forced, viscous Burger’s equation. Finally, finite filter widths are also considered, and both a priori and a posteriori analyses of temporal similarity and temporal approximate deconvolution models of the residual stress are conducted for the model problem.
The decay of homogeneous anisotropic turbulence
Authors: Biferale L. , Boffetta G. , Celani A. , Lanotte A. , Toschi F. , Vergassola M.
Published: July 2003

We present the results of a numerical investigation of three-dimensional decaying turbulence with statistically homogeneous and anisotropic initial conditions. We show that at large times, in the inertial range of scales: (i) isotropic velocity fluctuations decay self-similarly at an algebraic rate which can be obtained by dimensional arguments; (ii) the ratio of anisotropic to isotropic fluctuations of a given intensity falls off in time as a power law, with an exponent approximately independent of the strength of the fluctuation; (iii) the decay of anisotropic fluctuations is not self-similar, their statistics becoming more and more intermittent as time elapses. We also investigate the early stages of the decay. The different short-time behavior observed in two experiments differing by the phase organization of their initial conditions gives a new hunch on the degree of universality of small-scale turbulence statistics, i.e., its independence of the conditions at large scales.
Dynamics of two-dimensional Rayleigh–Taylor bubbles for fluids with a finite density contrast
Authors: Abarzhi Snezhana I. , Glimm James , Lin An-Der
Published: July 2003

We study the motion of a two-dimensional coherent structure of bubbles and spikes in the Rayleigh–Taylor instability for fluids with a finite density contrast in the case of a small amplitude initial perturbation. The theoretical and numerical solutions for the system of conservation laws are found, and the dynamics of the bubble shape and velocity in the nonlinear regime is described. Good agreement between theory and simulations is achieved. A comparison to earlier models is performed.
Reduction of flow-induced forces on a circular cylinder using a detached splitter plate
Authors: Hwang Jong-Yeon , Yang Kyung-Soo , Sun Seung-Han
Published: July 2003

Control of flow-induced forces on a circular cylinder using a detached splitter plate is numerically studied for laminar flow. A splitter plate with the same length as the cylinder diameter is placed horizontally in the wake region. Suppressing the vortex shedding, the plate significantly reduces drag force and lift fluctuation; there exists an optimal location of the plate for maximum reduction. However, they sharply increase as the plate is placed further downstream of the optimal location. This trend is consistent with the experimental observation currently available in the case of turbulent wake.
Another exact solution for two-dimensional, inviscid sinh Poisson vortex arrays
Authors: Chow K. W. , Tsang S. C. , Mak C. C.
Published: July 2003

Arrays of vortices are considered for two-dimensional, inviscid flows when the functional relationship between the stream function and the vorticity is a hyperbolic sine. An exact solution as a doubly periodic array of vortices is expressed in terms of the Jacobi elliptic functions. There is a threshold value of the period parameter such that a transition from globally smooth distributions of vorticity to singular distributions occurs.
The influence of a uniform magnetic field on the Soret coefficient of magnetic nanoparticles
Authors: Völker T. , Odenbach S.
Published: July 2003

Investigations were made to determine the Soret coefficient of magnetic particles in a ferrofluid. Based on zero field measurements from which the Soret coefficient is quantitatively determined with a theoretical model, the influence of a magnetic field on this parameter will be shown. A clear dependence of the intensity of the thermodiffusive process on the magnetic field strength could be found. In addition it could be shown, that the direction of the field relative to the driving temperature gradient has a significant influence too. In particular a change of the sign of the Soret coefficient was observed if the magnetic field is orientated parallel to the temperature gradient.
High critical current densities in Cu-sheathed MgB2 formed from a mechanically-alloyed precursor
Authors: Strickland N. M. , Buckley R. G. , Otto A.
Published: July 2003

Mechanical alloying is used to produce a metallic precursor for MgB2 formation. Micron-scale mixing of magnesium and boron powders allows the MgB2 formation reaction to proceed at as low as 450 °C, with high-quality material formed in an hour at 600 °C. These low reaction temperatures allow the reaction to be performed in situ in a copper sheath. Critical current densities, calculated from a full critical-state simulation of magnetization hysteresis loops, are up to 7×105 A/cm2 at 13.6 K and 1×105 A/cm2 at 30 K, in zero applied field.