bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of isolectin B4‐conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation
Authors: Nishiguchi Jun , Sasaki Katsumi , Seki Satoshi , Chancellor Michael B. , Erickson Kristin A. , De Groat William C. , Kumon Hiromi , Yoshimura Naoki 
Published: July 2004

AbstractIn order to clarify the functional role of the isolectin B4 (IB4)‐binding afferent pathway in the micturition reflex, we investigated the effects on bladder activity of intrathecal application of the IB4–saporin conjugate, a targeting cytotoxin that destroys neurons binding IB4. In rats, IB4–saporin (2.5 µm) or vehicle was administered through an intrathecal catheter implanted at the level of the L6–S1 spinal cord. Three weeks after IB4–saporin administration, cystometry in conscious animals revealed a reduction in bladder overactive responses induced by intravesical capsaicin or ATP infusion without affecting normal voiding function. In histochemical studies, double staining for IB4 and saporin was detected in L6 dorsal root ganglia (DRG) neurons 2 days after the treatment. Three weeks after the treatment, the area in lamina II of the L6 spinal cord stained with IB4 was significantly reduced compared with the area stained in control rats. The staining in the L1 spinal cord was not affected. The percentage of neurons in the L6 DRG intensely labeled with IB4 was also reduced in IB4–saporin‐treated rats. These results indicate that intrathecal treatment with the IB4–saporin conjugate at the level of L6–S1 spinal cord, which reduces IB4 afferent nerve terminal staining in lamina II of the L6 spinal cord as well as the number of IB4‐binding neurons in L6 DRG, suppressed bladder overactivity induced by bladder irritation without affecting normal micturition. Thus targeting IB4‐binding, non‐peptidergic afferent pathways sensitive to capsaicin and adenosine 5′‐triphosphate may be an effective treatment for overactivity and/or pain responses in the bladder.
Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues
Authors: Zugaro Michaël B. , Arleo Angelo , Déjean Cyril , Burguière Eric , Khamassi Mehdi , Wiener Sidney I. 
Published: July 2004

AbstractHead direction cells, which are functionally coupled to ‘place’ cells of the hippocampus, a structure critically involved in spatial cognition, are likely neural substrates for the sense of direction. Here we studied the mechanism by which head direction cells are principally anchored to background visual cues [M.B. Zugaro et al. (2001) J. Neurosci., 21, RC154,1–5]. Anterodorsal thalamic head direction cells were recorded while the rat foraged on a small elevated platform in a 3‐m diameter cylindrical enclosure. A large card was placed in the background, near the curtain, and a smaller card was placed in the foreground, near the platform. The cards were identically marked, proportionally dimensioned, subtended the same visual angles from the central vantage point and separated by 90°. The rat was then disoriented in darkness, the cards were rotated by 90° in opposite directions about the center and the rat was returned. Preferred directions followed either the background card, foreground card or midpoint between the two cards. In continuous lighting, preferred directions shifted to follow the background cue in most cases (30 of the 53 experiments, Batschelet V‐test, P < 0.01). Stroboscopic illumination, which perturbs dynamic visual signals (e.g. motion parallax), blocked this selectivity. Head direction cells remained equally anchored to the background card, foreground card or configuration of the two cards (Watson test, P > 0.1). This shows that dynamic visual signals are critical in distinguishing typically more stable background cues which govern spatial neuronal responses and orientation behaviors.
Complete Freunds adjuvant‐induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS
Authors: Raghavendra Vasudeva , Tanga Flobert Y. , DeLeo Joyce A. 
Published: July 2004

AbstractPeripheral inflammation induces central sensitization characterized by the development of allodynia and hyperalgesia to mechanical and thermal stimuli. Recent evidence suggests that activation of glial cells and a subsequent increase in proinflammatory cytokines contribute to the development of behavioral hypersensitivity after nerve injury or peripheral inflammation. In the present study, we examined mRNA and protein expression of glial markers and proinflammatory cytokines at the lumbar spinal cord, brainstem and forebrain following intraplantar administration of complete Freunds adjuvant (CFA) in rats. Gene expression studied by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) for microglial markers (Mac‐1, TLR4 and CD14) showed a significant increase in their expression during all phases (acute, subacute and chronic) of inflammation. Conversely, up‐regulation of astroglial markers [glial fibrillary acidic protein (GFAP) and S100B] was observed only at the subacute and chronic phases of inflammation. Increased immunoreactivity for OX‐42 (CR3/CD11b) and GFAP at various brain regions was also observed after the acute and subacute phases of the inflammation, respectively. Quantification of proinflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) at the mRNA (by real‐time RT‐PCR) and protein level (by ELISA) revealed enhanced expression during the acute, subacute and chronic phases of CFA‐induced peripheral inflammation. This study demonstrates that CFA‐induced peripheral inflammation induces robust glial activation and proinflammatory cytokines both spinally and supraspinally. In addition, similar to nerve injury‐induced behavioral hypersensitivity microglial activation preceded astrocytic activation following CFA‐induced peripheral inflammation, supporting a role of microglia in the initiation phase and astrocytes in maintaining hypersensitivity. These findings further support a unifying theory that glial activation and enhanced cytokine expression at the CNS have a role in eliciting behavioral hypersensitivity.
Functional MRI during sleep: BOLD signal decreases and their electrophysiological correlates
Authors: Czisch Michael , Wehrle Renate , Kaufmann Christian , Wetter Thomas C. , Holsboer Florian , Pollmächer Thomas , Auer Dorothee P. 
Published: July 2004

AbstractProminent local decreases in blood oxygenation level (BOLD) can be observed by functional magnetic resonance imaging (fMRI) upon acoustic stimulation during sleep. The goal of this study was to further characterize this BOLD signal decrease with respect to corresponding neurophysiological phenomena using a simultaneous electroencephalography (EEG)/fMRI approach in sleeping human subjects. Healthy volunteers were subjected to acoustic stimulation during non‐rapid eye movement (NREM) sleep. On the basis of statistical parametric maps, the correlations between the fMRI response (both amplitude and extent of the BOLD response) and the concomittant changes in the EEG (delta power and K‐complexes) were calculated. Amplitude and extent of the stimulus‐induced negative BOLD effect correlated positively with measures of EEG synchronization, namely an increase in the number of K‐complexes and EEG delta power. Stimulus‐induced BOLD decreases were most prominent during light (stage 2) NREM sleep and disappeared during slow wave sleep, indicating an influence of the baseline degree of hyperpolarization. Our observations provide first evidence that ‘negative’ BOLD signal changes during human sleep are associated with electrophysiological indicators of altered neuronal activity. Increased number of K‐complexes and delta power reflecting hyperpolarization suggests true cortical deactivation upon stimulus presentation. This sleep stage‐dependent deactivation might serve to protect the brain from arousing stimuli, particularly during the light phases of sleep shortly after sleep onset.
Selective Schools
Authors: Brunello Giorgio , Giannini Massimo 
Published: July 2004

AbstractThis paper studies how schooling admission tests affect economic performance in an economy where individuals are endowed with both academic and non‐academic abilities and both abilities matter for labour productivity. We develop a simple model with schools run by the goverment, where individuals signal their abilities by taking an admission test and sort into low quality and high quality schools. When abilities are poorly correlated in the population, as documented in the literature, a standard test based only on academic abilities can be less efficient than a balanced test, which considers both ability types. We show that a sequential testing strategy, with schools testing academic abilities and firms testing non‐academic abilities on the sub‐sample of graduates of high quality schools, does not necessarily replicate the outcome of a balanced test.
Compulsory Schooling Laws and the Cure for Child Labour
Authors: Bellettini Giorgio , Ceroni Carlotta Berti 
Published: July 2004

AbstractThis paper provides an explanation for the existence of child labour which relies on the imperfect enforcement of compulsory schooling laws. In the presence of complementarities in the production of human capital that justify legislative intervention, mandatory measures ensure that coordination failures are solved so that all parents send their children to school and the socially optimal equilibrium is reached. However, if enforcement of legislation is too low, multiple equilibria emerge. In this case, compulsory schooling laws may have adverse welfare effects on all households.
The Delaying Effect of Financing Constraints on Investment
Authors: Van De Laar Mindel , Letterie Wilko 
Published: July 2004

AbstractWe develop a simple model in which a firm considers a number of investment projects. Because of limited financial resources, the firm can undertake at most one project. In line with the literature on real options we stress features like irreversibility, uncertainty and the possibility of postponing the investment decision and show under which conditions limited availability of funds tends to increase the value of waiting.
RADICAL ORTHODOXY AND THE NEW CULTURE OF OBSCURANTISM
Authors: JANZ PAUL D. 
Published: July 2004

AbstractCentering around a careful, sustained critique of John Milbank's polemic against Kant, this essay connects the growing anti‐philosophical sentiments in theology to a wider anti‐rational trend in the human sciences generally. What most visibly unifies these new obscurantist outlooks is their reliance on free‐floating, unapologetically self‐perpetuating ideological historiographies, which are advanced via a kind of “co‐opt‐and‐plunder” approach to historical texts. However, the rejection of rational integrity also entails a rejection of the traditional intellectual virtues—attentiveness, consistency, modesty, charity etc.—virtues which any theological claim to orthodoxy cannot do without. Radical Orthodoxy therefore risks a worrying slide into new forms of esoteric gnosticism.
William Warham and English heresy policy after the fall of Wolsey
Authors: D'Alton Craig 
Published: July 2004

Abstract
This article examines actions against heresy and heretics in England in the wake of the 1529 fall of Cardinal Thomas Wolsey. It charts the brief re-emergence of William Warham, archbishop of Canterbury, as the main driving force, arguing that the lord chancellor, Sir Thomas More, did not assert control over heresy policy until late 1531. Warham's policy combined anti-heresy activity with attempts at clerical reform. Moreover, he sought to publicize and publicly refute the errors of the heretics, eschewing show trials and burnings. This policy ultimately failed, and was replaced with more direct action which saw several key heretics handed over for burning.
The Hitler émigrés: the cultural impact on Britain of refugees from Nazism
Authors: Snowman Daniel 
Published: July 2004

Abstract
This article reflects upon some of the issues arising from the author's work on the ‘Hitler émigrés’. It looks in particular at the reasons for the huge recent resurgence of scholarly (and popular) interest in the history of the Second World War, Hitler, Nazism and the Holocaust; the relevance – or otherwise – of the Jewishness of many of the ‘Hitler émigrés’ to what they went on to achieve; and finally culture and identity among asylum-seekers and immigrants, then and now.
The breakdown of starch in leaves
Authors: Zeeman Samuel C. , Smith Steven M. , Smith Alison M. 
Published: July 2004

SummaryThis review describes recent progress in discovering the pathway of starch breakdown in leaves. The synthesis of starch from photo‐assimilated carbon is one of the major biochemical fluxes in plants. Despite this, the pathway through which this starch is remobilized has not been defined. Numerous enzymes that could participate in starch breakdown are present in leaves, but until recently, the relative importance of each had not been determined. Through studies using model species such as Arabidopsis and potato, significant progress has now been made in determining the roles of known enzymes, and in the discovery of novel proteins necessary for breakdown. These data allow a tentative pathway for starch breakdown to be mapped out, involving hydrolysis primarily to maltose and subsequent maltose export to the cytosol. This provides a framework for complete discovery of the pathway and for the analysis of its regulation.

Contents

Summary
247

I.
Introduction
247

II.
Structure of the starch granule
248

III.
Initial attack on the granule and the role of glucan, water dikinase
249

IV.
Debranching of branched glucans
250

V.
The metabolism of linear glucans
251

VI.
Export of starch catabolites
254

VII.
Metabolism of glucose and maltose
255

VIII.
The emerging pathway of starch breakdown and its regulation
256

Acknowledgements
258

References
258
The plant nuclear envelope: new prospects for a poorly understood structure
Authors: Brandizzi Federica , Irons Sarah L. , Evans David E. 
Published: July 2004

SummaryThe nuclear envelope (NE) is one of the least characterized cellular structures in plant cells. In particular, knowledge of its dynamic behaviour during the cell cycle and of its protein composition is limited. This review summarizes current views on the plant NE and highlights fundamental differences with other organisms. We also introduce the power of new technology available to investigate the NE and how this has already begun to revolutionize our knowledge of the biology of the plant NE.

Contents

Summary
227

I.
Introduction
227

II.
The membranes of the nuclear envelope
228

III.
Functions of the nuclear envelope
231

IV.
Proteins associated with the nuclear envelope
236

V.
New tools for studying the nuclear envelope
239

VI.
Conclusions and future prospects
241

Acknowledgements
242

References
242
Developmental differences in H2O2‐induced oligodendrocyte cell death: role of glutathione, mitogen‐activated protein kinases and caspase 3
Authors: Fragoso Gabriela , Martínez‐Bermúdez Ana Katherine , Liu Hsueh‐Ning , Khorchid Amani , Chemtob Sylvain , Mushynski Walter E. , Almazan Guillermina 
Published: July 2004

AbstractThe molecular mechanisms underlying H2O2‐induced toxicity were characterized in rat oligodendrocyte cultures. While progenitor cells were more sensitive than mature oligodendrocytes to H2O2, the antioxidant, N‐acetyl‐l‐cysteine, blocked toxicity at both stages of development. Differentiated oligodendrocytes contained more glutathione than did progenitors and were less susceptible to decreases in glutathione concentration induced by H2O2 stress. As free radicals have been considered to serve as second messengers, we examined the effect of H2O2 on activation of the mitogen‐activated protein kinases (MAPK), extracellular signal‐regulated kinases (ERK) 1/2 and p38. H2O2 caused a time‐ and concentration‐dependent increase in MAPK phosphorylation, an effect that was totally blocked by N‐acetyl‐l‐cysteine. Further exploration of potential mechanisms involved in oligodendrocyte cell death showed that H2O2 treatment caused DNA condensation and fragmentation at both stages of development, whereas caspase 3 activation and poly (ADP‐ribose) polymerase cleavage were significantly increased only in oligodendrocyte progenitors. The pan‐caspase inhibitor, benzyloxycarbonyl‐Val‐Ala‐Asp fluoromethyl ketone, blocked DNA fragmentation in progenitors and produced a small but significant level of protection from H2O2 toxicity in progenitors and mature oligodendrocytes. In contrast, inhibitors of both p38 and MEK reduced H2O2‐induced death most significantly in oligodendrocytes. The poly (ADP‐ribose) polymerase inhibitor, PJ34, reduced H2O2‐induced toxicity on its own but was most effective when combined with benzyloxycarbonyl‐Val‐Ala‐Asp fluoromethyl ketone or PD169316. The finding that molecular mechanisms conferring resistance to reactive oxygen species toxicity are regulated during oligodendrocyte differentiation may be of importance in designing therapies for certain neurological diseases affecting white matter.
Angiotensin II regulates tyrosine hydroxylase activity and mRNA expression in rat mediobasal hypothalamic cultures: the role of specific protein kinases
Authors: Ma Frank Y. , Grattan David R. , Bobrovskaya Larisa , Dunkley Peter R. , Bunn Stephen J. 
Published: July 2004

AbstractDopamine secreted by hypothalamic neurons is crucial in regulating prolactin secretion from the pituitary. We have examined the ability of angiotensin II (AngII) to regulate the activity of these dopaminergic neurons and thus act as a potential physiological regulator of prolactin secretion. Using a hypothalamic cell culture preparation we determined the effect of AngII on tyrosine hydroxylase activity and expression (TOH). This is important because TOH is the rate‐limiting enzyme in dopamine biosynthesis. AngII stimulated a time‐ and concentration‐dependent increase in TOH activity which was suppressed by inhibitors able to act on protein kinase A (PKA), protein kinase C (PKC) and Ca2+/calmodulin‐dependent protein kinase II (CaMPKII). An inhibitor of the mitogen‐activated protein kinase (MAPK) pathway, PD 98059, reduced basal TOH activity but the AngII response was still detectable. AngII stimulation enhanced the phosphorylation of TOH at Ser19, Ser31 and Ser40. AngII also induced a time‐dependent increase in TOH mRNA expression which was unaffected by inhibitors able to act on PKA and CaMPKII, but was abolished by inhibitors able to act on ERK and PKC. AngII responses were very much larger in cultures prepared from female when compared to male rat pups. Data from adult hypothalamic slices confirmed this sexual dimorphism and supported the role of the protein kinases noted above. Therefore AngII can regulate both the activity and expression of TOH in hypothalamic neurons employing multiple, but only partially overlapping, signaling pathways.
Interference with ubiquitination causes oxidative damage and increased protein nitration: implications for neurodegenerative diseases
Authors: Hyun Dong‐Hoon , Gray Douglas A. , Halliwell Barry , Jenner Peter 
Published: July 2004

AbstractInhibition of the proteasomal pathway for degrading abnormal proteins leads to protein aggregation, increased oxidative damage and increased protein nitration. We now show that interference with polyubiquitination has similar consequences. Expression of a dominant‐negative mutant form of ubiquitin (K48R) in NT‐2 and SK‐N‐MC cells caused decreased cell growth rates and increased oxidative damage (protein carbonyls and lipid peroxidation), nitric oxide production and elevated protein nitration. It also rendered cells highly sensitive to 4‐hydroxy‐2,3‐trans‐nonenal, a neurotoxic end‐product of lipid peroxidation, hydrogen peroxide and deprivation of growth factors. Overexpression of wild‐type ubiquitin did not produce these effects. Our data show that interference with the ubiquitin‐proteasome pathway at a different point and by a different mechanism can produce many of the common features of human neurodegenerative diseases, such as increased lipid peroxidation, protein oxidation and protein nitration. We suggest that defects in this pathway at multiple points could produce the common features of neurodegenerative diseases, and that more such defects remain to be discovered.
A novel peptide modulates α7 nicotinic receptor responses: implications for a possible trophic‐toxic mechanism within the brain
Authors: Greenfield Susan A. , Day Toni , Mann Edward O. , Bermudez Isabel 
Published: July 2004

AbstractThe α7 nicotinic acetylcholine receptor (nAChR) plays a key role in neural development and neurodegeneration. Here, we identify a novel, modulatory receptor ligand, a 14‐amino acid peptide (AEFHRWSSYMVHWK) derived from the C‐terminus of acetylcholinesterase (AChE). In three different in vitro preparations, this ‘AChE‐peptide’ is bioactive in a ligand‐specific and concentration‐dependent manner. First, it modulates acutely the effect of acetylcholine (ACh) on Xenopus oocytes transfected with human α7, but not α4/β2, nAChR. The action persists when intracellular calcium is chelated with BAPTA or when calcium is substituted with barium ions. This observation suggests that intracellular Ca2+ signals do not mediate the interaction between the peptide and nAChR, but rather that the interaction is direct: however, the intervention of other mediators cannot be excluded. Secondly, in recordings from the CA1 region in guinea‐pig hippocampal slices, AChE‐peptide modulates synaptic plasticity in a α‐bungarotoxin (α‐BgTx)‐sensitive manner. Thirdly, in organotypic cultures of rat hippocampus, long‐term exposure to peptide attenuates neurite outgrowth: this chronic, functional effect is selectively blocked by the α7 nAChR antagonists, α‐BgTx and methyllycaconitine, but not by the α4/β2‐preferring blocker dihydro‐β‐ethroidine. A scrambled peptide variant, and the analogous peptide from butyrylcholinesterase, are ineffective in all three paradigms. The consequences of this novel modulation of the α7 nAChR may be activation of a trophic‐toxic axis, of relevance to neurodegeneration.
Protein kinase C regulates the activity and stability of serotonin N‐acetyltransferase
Authors: Choi Bo‐Hwa , Chae Hee‐Don , Park Tae‐Ju , Oh Jisun , Lim Jinkyu , Kang Shin‐Sung , Ha Hyunjung , Kim Kyong‐Tai 
Published: July 2004

AbstractEffects of protein kinase C on protein stability and activity of rat AANAT were investigated in vitro and in vivo. When COS‐7 cells transfected with AANAT cDNA were treated with phorbol 12‐myristate 13‐acetate (PMA), both the activity and protein level of AANAT were increased. These effects of PMA were blocked by GF109203X, a specific inhibitor of PKC. Moreover, PMA increased the phosphorylation of AANAT and induced the formation of AANAT/14‐3‐3ζ complex. PMA did not affect the basal level of cAMP and did not involve the potentiation of the cAMP production by forskolin, indicating that PKC‐dependent activation of adenylyl cyclase was excluded in transfected COS‐7 cells. To identify which amino acids were phosphorylated by PKC, several conserved Thr and Ser residues in AANAT were targeted for site‐directed mutagenesis. Mutations of Thr29 and Ser203 prevented the increase of enzymatic activity and protein level mediated by PMA. To explore the nature of AANAT phosphorylation, purified rat AANAT was subjected to in vitro PKC kinase assay. PKC directly phosphorylated the rat recombinant AANAT. The phosphopeptides identified by mass spectrometric analysis, and western blotting indicated that Thr29 was one of target sites for PKC. To confirm the effects of the physiological activation of PKC, rat pineal glands were treated with α1‐adrenergic specific agonist phenylephrine. Phenylephrine caused the phosphorylation of endogenous AANAT whereas GF109203X or prazosin, an α1‐adrenergic‐specific antagonist, markedly inhibited it. These results suggest that AANAT was phosphorylated at Thr29 by PKC activation through the α1‐adrenergic receptor in rat pineal glands, and that its phosphorylation might contribute to the stability and the activity of AANAT.