bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the Expanded Disability Status Scale and Multiple Sclerosis Functional C omposite
Authors: Hobart J , Kalkers N , Barkhof F , Uitdehaag B , Polman C , Thompson A
Published: February 2004

We compared the relative measurement precision (RMP) of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functio nal C omposite (MSFC) for discriminating between groups of patients known to differ in their extent of multiple sclerosis (MS). A total of 133 patients were rated with the EDSS and MSFC and had magnetic resonance imaging (MRI) scans. Patients were grouped on the basis of MRI appearances (T1- and T2-weighted lesion loads, parenchymal and ventricular fractions - T1LL, T2LL, PF, VF, respectively) and RMP was determined using the method of group differences. For each MRI parameter, the total sample was arranged in ascending order of magnitude and divided into two, three, four and five similar sized groups. For each division (two, three, four or five groups), EDSS and MSFC scores for the groups were compared using parametric (paired samples t-tests, one-way A NOVA) and nonparametric (Wilcoxon’s rank-sum test, Kruskal -Wallis analysis of variance) statistical methods and RMP was estimated. The EDSS and MSFC were correlated substantially (r = -0.64). Relative to the MSFC, the EDSS had inferior measurement precision regardless of the number of groups into which the total sample was divided, or the statistical method. However, the RMP of the EDSS compared with the MSFC varied from 2% to 86%. Results suggest the MSC F is better than the EDSS for detecting differences between groups of patients, defined by these MRI markers of MS. However, the finding that both scales correlated weakly with MRI markers, indicated that they are limited as predicto rs of MS patho logy as defined by MRI. A n explanatio n for this well-established clinical -MRI paradox is that rating scales and MRI measure fundamentally different manifestations of MS.
Scleromyxedema in a patient with multiple sclerosis and monoclonal gammopathy on interferon beta-1a
Authors: Kumar Neeraj , Rodriguez Moses
Published: February 2004

Background: Animal studies have shown that some human monoclonal antibodies promote myelin repair in models of demyelinating disease. Scleromyxedema is a dermatologic disorder associated with a monoclonal gammopathy and neurologic manifestations. The reason for occurrence of cutaneous reactio ns in interferon treated patients is unknown. Case description: A 37-year-o ld woman was started on weekly interferon beta-1a (IFN beta-1a) following a diagnosis of multiple sclerosis (MS). A fter having been on interferon therapy for three years, she developed skin lesions secondary to scleromyxedema. Her IFN beta-1a was discontinued and intravenous immunoglobulin therapy was started for her scleromyxedema. A t a six-month follow up, her skin lesions improved and there was no recurrence of neurologic symptoms. Conclusions: This is the first report of occurrence of scleromyxedema in a patient with MS. While this could be a chance association, it does raise the question if her neurologic manifestations could be secondary to scleromyxedema. Further research into the mechanism of IFN related cutaneo us side effects is needed. Evidence regarding the remyelinating nature of human monoclonal antibodies raises interest in the potential therapeutic role these antibodies may have.
Alkanoylsucroses in nasal delivery of low molecular weight heparins: in-vivo absorption and reversibility studies in rats
Authors: Yang Tianzhi , Mustafa Fatima , Ahsan Fakhrul
Published: January 2004

The efficacy of alkanoylsucroses in enhancing nasal absorption of low molecular weight heparin (LMWH) and the time span of action of these agents on the nasal membrane has been investigated. In this regard, LMWH formulated with alkanoylsucroses was administered nasally to anaesthetized male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. The duration of action of these agents at the site of administration was investigated by an in-vivo reversibility study. The potency and efficacy of dodecanoylsucrose was compared with that of sodium glycocholate. Alkanoylsucroses used in this study include dodecanoylsucrose, decanoylsucrose and octanoylsucrose. These agents enhance nasal absorption of enoxaparin in a dose-dependent and chain-length-dependent manner. Of the agents tested, dodecanoylsucrose was found to be the most potent in enhancing nasal absorption of LMWH. The bioavailability of enoxaparin formulated with alkanoylsucroses was increased by several folds compared with enoxaparin formulated in saline. The reversibility study with dodecanoylsucrose showed that the effect of alkanoylsucroses faded away with time and the duration of action of this agent at the site of administration was 120–140 min. Dodecanoylsucrose was found to be twice as potent as sodium glycocholate. Overall, the nasal absorption of LMWH was effectively enhanced by co-administration of alkanoylsucroses and the effect of alkanoylsucroses on nasal epithelium was found to be reversible. The potency of these agents depends on their hydrophobic chain lengths.
Vitamin E prevents buthionine sulfoximine-induced biochemical disorders in the rat
Authors: Rajasekaran Namakkal Soorappan , Devaraj Niranjali S , Devaraj Halagowder
Published: January 2004

Antioxidant therapy can improve the protection and metabolic activity of cells and tissues. In this study, the effect of vitamin E administration on buthionine sulfoximine (BSO)-induced glutathione (GSH) depletion in the rat lung and liver was investigated. Hepatic GSH was depleted by intraperitoneal administration of BSO (4 mmol kg−1), twice a day, for 30 days to rats. We also investigated whether the lung and liver mitochondrial GSH contents were influenced by BSO administration and whether an extracellular supply of vitamin E could prevent the changes caused by BSO-mediated GSH depletion. Glutathione levels in lung and liver tissues were depleted by 47% and 60%, respectively. Depletion of hepatic and pulmonary GSH in turn causes decline in the levels of mitochondrial GSH, leading to impaired antioxidant defence function of mitochondria. Both the cytosolic and mitochondrial glutathione disulfides (GSSG) were altered during BSO treatment, and led to drastic increase in GSSG/GSH redox status. One of the experimental groups was given vitamin E (65 mg (kg diet)−1) mixed with rat feed. The rats fed with vitamin E were found to have partially restored GSH levels in liver and lung, diminished levels of TBARS and minimized tissue damage. The current findings suggest that the impaired glutathione and glutathione-dependent enzyme status may be correlated with the elevated lipid peroxidation and mitochondrial membrane damage and that vitamin E therapy to the BSO-administered rats prevents the above changes. However, vitamin E did not have any effect on the activity of γ-glutamyl cysteine synthetase (γ-GCS).
Preparation of DNA dry powder for non-viral gene delivery by spray-freeze drying: effect of protective agents (polyethyleneimine and sugars) on the stability of DNA
Authors: Kuo Jung-hua Steven , Hwang Robin
Published: January 2004

This study investigates the feasibility of using the process of spray-freeze drying (SFD) to produce DNA dry powders for non-viral gene delivery. The effect of protective agents was assessed on the stability of DNA dry powders after SFD. The process of SFD had adverse effects on the tertiary structure of DNA with the protective agents of sucrose, trehalose and mannitol. With the protection of these sugars, a band corresponding to the linear form of DNA was observed during gel electrophoresis between the supercoiled form (SC) and the open circular (OC) form. On the contrary, excess cationic condensing polyethyleneimine (PEI), in conjunction with the above sugars, had the ability to provide protection for DNA from degradation after SFD. This is indicated by the reservation in SC and OC forms of DNA during agarose gel electrophoresis. The electrostatic forces between PEI polymer and DNA are critical for providing protection against various stresses generated by the process of SFD. Furthermore, on rehydration, the particle size and zeta potential of PEI/DNA complexes at weight ratios 3:1 of SFD dry powders were well maintained. Also, no transfection activity loss of PEI/DNA complexes at weight ratios 3:1 on NIH/3T3 cells was observed for reconstituted powders as compared with untreated control solutions. These results give a better understanding of preparing stable DNA dry powders by the process of SFD.
Morphogens, their identification and regulation
Authors: Tabata Tetsuya , Takei Yuki
Published: February 2004

During the course of development, cells of many tissues differentiate according to the positional information that is set by the concentration gradients of morphogens. Morphogens are signaling molecules that emanate from a restricted region of a tissue and spread away from their source to form a concentration gradient. As the fate of each cell in the field depends on the concentration of the morphogen signal, the gradient prefigures the pattern of development. In this article, we describe how morphogens and their functions have been identified and analyzed, focusing on model systems that have been extensively studied.
Remarkable Differences in Photo and Thermal (Acid-catalyzed) Reactivities between ortho- and para-Acylcyclohexadienones as Essential Factors Determining the Overall Efficiency of the Photo-Fries Rearrangement
Authors: Mori Tadashi , Takamoto Makoto , Saito Hideaki , Furo Takahiro , Wada Takehiko , Inoue Yoshihisa
Published: February 2004

Successful isolation of “ortho” and “para”-acylcyclohexadienones allowed us to comparatively study their ground- and excited-state behavior under a variety of conditions. In neutral solutions, the two isomeric cyclohexdienones showed completely different reactivities for photochemical and thermal reactions, while in acidic methanol both quantitatively afforded the corresponding transesterification product and naphthol. These studies help us understand the detailed photo-Fries rearrangement mechanism, which involves several crucial photochemical and thermal steps.
Amphiphilic Cyclodextrins as Novel Monosaccharide Transport Carriers through a Bulk Liquid Membrane
Authors: Kida Toshiyuki , Ohe Takeru , Higashimoto Hiroyuki , Harada Hitoshi , Nakatsuji Yohji , Ikeda Isao , Akashi Mitsuru
Published: February 2004

Monosaccharides, such as d-ribose, d-xylose, and d-glucose, were successfully transported through a bulk liquid membrane by using amphiphilic cyclodextrin carriers. The transport ability was remarkably affected by the lipophilicity and ring size of the carrier molecule.
Rapid Crystallization of High Quality Cubic Sillica SBA-16 Nanoporous Material
Authors: Cheng Chi-Feng , Lin Yi-Chun , Cheng Hsu-Hsuan , Liu Shr-Miau , Sheu Hwo-Shuenn
Published: February 2004

High quality cubic SBA-16 can be synthesized rapidly at room temperature in 1 h using low surfactant concentrations and has 65% of micropore volume and 5.3 nm of wall thickness on average. The structure integrity of SBA-16 is very sensitive to the acid concentration in gel because of the necessity of moderate hydrogen-bonding and electrostatic interaction between silicates and surfactants.
Direct Speciation of Tin Compounds in Environmental Samples Using Sn K-edge XANES
Authors: Sakakibara Naoki , Takahashi Yoshio , Yamaguchi Yoshitaka , Shibata Kiyoshi , Uruga Tomoya
Published: February 2004

Tin K-edge XANES spectra show systematic broadening in the first peak upon increasing the number of organic ligands coordinated to the Sn atom, which can be used to determine Sn speciation in environmental samples. Although the method only provides the average number of organic ligands bound to Sn, a direct method like XANES for Sn speciation can be useful in view of the difficulties associated with chromatographic methods for Sn speciation.
Synthesis of Meso-/Macroporous Zeolite (Fe,Al)-ZSM-5 Microspheres from Diatomite
Authors: Shan Wei , Zhang Yahong , Wang Yajun , Xia Jianchao , Tang Yi
Published: February 2004

Microspheres of (Fe,Al)-ZSM-5 crystallite aggregates with abundant meso-/macropores have been synthesized by hydrothermal treatment of natural diatomite in a NaCl-containing solution. It was found that the addition of NaCl would lead to the formation of spherical product as well as promoting the incorporation of the Fe originally existed in diatomite into zeolitic framework.
An Efficient and Green Synthesis of 2-Arylbenzothiazoles in an Ionic Liquid, [pmIm]Br under Microwave Irradiation
Authors: Ranu Brindaban C , Jana Ranjan , Dey Suvendu S
Published: February 2004

An efficient and green procedure for the synthesis of 2-arylbenzothiazoles has been developed by a simple condensation of 2-aminothiophenol and aromatic aldehyde in an inexpensive ionic liquid, 1-pentyl-3-methylimidazolium bromide ([pmIm]Br) by microwave irradiation under solvent and catalyst-free condition. The ionic liquid is recycled for subsequent reactions.
Do otolaryngology out-patients use the internet prior to attending their appointment?
Authors: Tassone Peter , Georgalas Christos , Patel Nimesh N. , Appleby Esther , Kotecha Bhik
Published: January 2004

The Internet has become a very important source of health information. We wanted to determine otolaryngology patients’ access to, and use of, the Internet as a medical information resource, to identify factors that make patients more likely to use it, and to determine how useful they find this information.

A questionnaire survey was completed by patients while waiting for their consultation in the out-patient department of the Royal National Throat Nose and Ear Hospital in London. Five hundred and thirty-five questionnaires were completed. Sixty-four per cent (344/535) reported having access to the Web. Of the 344 with access, 62 (18 per cent) had searched the Web for medical information prior to their consultation. Higher education (p <0.001) and age between 18 and 40 years (p = 0.001) correlated significantly with higher Internet use. Ninety-five per cent planned to use the Internet again.

Approximately one out of five otolaryngology out-patients with Internet access reported having obtained medical information from the Web before their consultation. The majority found it helpful to some degree and were planning to use it again. As clinicians we should be aware ofthis use and the onus should be on ourselves to review these sites in order to guide our patients to sources of reliable and helpful medical information on the Internet.
Waiting-list prioritization in the National Health Service
Authors: Prasad S. , Kapoor P. K. D. , Kumar Aneesh , Reddy K. T. V. , Kumar B. N.
Published: January 2004

The aim of this study was to find out whether there is a consensus of opinion among healthcare providers and different sections of the public on the relative prioritization of common otolaryngological conditions for outpatient consultations and inpatient treatment. ENT consultants, general practitioners, administrators, NHS employees, non-ENT patients and members of the general public were given common scenarios of otolaryngological conditions and asked to prioritize them in order of importance. All the groups gave top priority for patients with suspected cancer of the larynx (outpatients) and for surgical treatment of cancer. Children with hearing problems were more commonly ranked in the top three categories than children requiring treatment for sore throats. All groups assigned those requiring rhinoplasty, treatment for snoring or hearing aids to the last three ranks. This study shows that there is a remarkable uniformity of opinion in determining clinical priorities which is similar to the traditional policies practised by UK ENT consultants.
An alternative use of the surgical mask for the protection of healthcare workers managing epistaxis
Authors: Gwilym Stephen , Armstrong Ruth , Kundu Sujata , Steventon Nicholas
Published: January 2004

Epistaxis has a reported prevalence of 10–12 per cent in the general population and is thus one of the commonest emergencies in Otolaryngology. We suggest that the patient uses a surgical mask to prevent blood spray during epistaxis management. Utilizing the described technique we have found that protective clothing worn by the healthcare professional is consistently ’blood-free’ atthe end of the procedure. This is in contrast to findings when no facemask is applied.
Sweet’s syndrome affecting the external auditory canal and tympanic membrane
Authors: Saliba Walid R. , Goldstein Lee H. , Habib George S. , Elias Mazen S.
Published: January 2004

We report a patient who developed left ear pain, dry cough, and fever. The external auditory canal was tender, swollen, erythematous and full of debris. Later the patient developed widespread tender and red skin nodules and pustules that subsequently coalesced to form plaques. Identical lesions developed also in the external auditory canal and the tympanic membrane of the affected ear. Skin biopsy showed dermal neutrophilia, compatible with the diagnosis of Sweet’s syndrome. Rapid improvement was achieved with prednisone after the failure of antibiotics.
Complicated otitis media caused by Fusobacterium necrophorum
Authors: Giridharan W. , De S. , Osman E. Z. , Amma L. , Hughes J. , McCormick M. S.
Published: January 2004

Fusobacterium necrophorum is implicated as an aetiological agent in a variety of necrotic diseases, such as Lemièrre’s syndrome (LS) in humans. LS was initially described as septic thrombophlebitis of the internal jugular vein secondary to an acute oropharyngeal infection. Other primary sources of infection include parotitis, otitis media, sinusitis, odontogenic infection and m stoiditis. In the pre-antibiotic era LS carried a high mortality. This has been reduced as a result of the widespread use of antibiotics, butthere is still a definite morbidity and mortality associated with infection with this virulent organism. We report three cases of complicatedotitis media caused by Fusobacterium necrophorum. The patients were treated successively with intravenous metronidazole and surgery.
Angiostrongylus eosinophilic meningitis associated with sensorineural hearing loss
Authors: Chotmongkol Verajit , Yimtae Kwanchanok , Intapan Pewpan M.
Published: January 2004

A 59-year-old woman who presented with chronic headache, neck stiffness and left-sided hearing loss is reported. The diagnosis of angiostrongylus eosinophilic menigitis was made. The patient improved after treatment with prednisolone, including hearing.Angiostrongylus eosinophilic meningitis associated with sensorineural hearing loss has not previously been reported.
Translamellar Disinhibition in the Rat Hippocampal Dentate Gyrus after Seizure-Induced Degeneration of Vulnerable Hilar Neurons
Authors: Zappone Colin A. , Sloviter Robert S.
Published: January 2004

Longitudinally restricted axonal projections of hippocampal granule cells suggest that transverse segments of the granule cell layer may operate independently (the “lamellar” hypothesis). Longitudinal projections of excitatory hilar mossy cells could be viewed as antithetical to lamellar function, but only if longitudinal impulse flow effectively excites distant granule cells. We, therefore, determined the effect of focal granule cell discharges on granule cells located >2 mm along the longitudinal axis. During perforant pathway stimulation in urethane-anesthetized rats, passive diffusion of the GABAAreceptor antagonist bicuculline methiodide from the tip of a glass recording electrode evoked granule cell discharges and c-Fos expression in granule cells, mossy cells, and inhibitory interneurons, within a ∼400 μm radius. This focally evoked activity powerfully suppressed distant granule cell-evoked responses recorded simultaneously ∼2.5–4.5 mm longitudinally. Three days after kainic acid-induced status epilepticus or prolonged perforant pathway stimulation, translamellar inhibition was intact in rats with <40% hilar neuron loss but was consistently abolished after extensive (>85%) hilar cell loss. Retrograde transport of Fluoro-Gold (FG) from the rostral dentate gyrus revealed that few inhibitory interneurons were among the many retrogradely labeled hilar neurons 2.5–4.5 mm longitudinally. Although many somatostatin-positive hilar interneurons effectively transported FG from the distant septum, few of these neurons transported detectable FG from much closer hippocampal injection sites. Inhibitory basket and chandelier cells also exhibited minimal longitudinal FG transport. These findings suggest that translamellar disinhibition may result from the loss of vulnerable, longitudinally projecting mossy cells and may represent a network-level mechanism underlying postinjury hippocampal dysfunction and epileptic network hyperexcitability.
Phox2a Gene, A6 Neurons, and Noradrenaline Are Essential for Development of Normal Respiratory Rhythm in Mice
Authors: Viemari J. C. , Bévengut M. , Burnet H. , Coulon P. , Pequignot J. M. , Tiveron M. C. , Hilaire G.
Published: January 2004

Although respiration is vital to the survival of all mammals from the moment of birth, little is known about the genetic factors controlling the prenatal maturation of this physiological process. Here we investigated the role of thePhox2agene that encodes for a homeodomain protein involved in the generation of noradrenergic A6 neurons in the maturation of the respiratory network. First, comparisons of the respiratory activity of fetuses delivered surgically from heterozygousPhox2apregnant mice on gestational day 18 showed that the mutants had impairedin vivoventilation,in vitrorespiratory-like activity, andin vitrorespiratory responses to central hypoxia and noradrenaline. Second, pharmacological studies on wild-type neonates showed that endogenous noradrenaline released from pontine A6 neurons potentiates rhythmic respiratory activity via α1 medullary adrenoceptors. Third, transynaptic tracing experiments in which rabies virus was injected into the diaphragm confirmed that A6 neurons were connected to the neonatal respiratory network. Fourth, blocking the α1 adrenoceptors in wild-type dams during late gestation with daily injections of the α1 adrenoceptor antagonist prazosin inducedin vivoandin vitroneonatal respiratory deficits similar to those observed inPhox2amutants. These results suggest that noradrenaline, A6 neurons, and thePhox2agene, which is crucial for the generation of A6 neurons, are essential for development of normal respiratory rhythm in neonatal mice. Metabolic noradrenaline disorders occurring during gestation therefore may induce neonatal respiratory deficits, in agreement with the catecholamine anomalies reported in victims of sudden infant death syndrome.
CRE-Mediated Transcription Is Increased in Huntington's Disease Transgenic Mice
Authors: Obrietan Karl , Hoyt Kari R.
Published: January 2004

Disruption of cAMP response element (CRE)-dependent transcription has been hypothesized to contribute to neuronal death and dysfunction in Huntington's disease (HD) and other polyglutamine repeat disorders. Whether dysregulation of CRE-dependent transcription actually occursin vivoin response to expression of expanded polyglutamine repeats has not been tested. We directly tested whether CRE-dependent transcription is affectedin vivoby cross breeding a transgenic mouse model of HD (line R6/2) with a transgenic mouse that expresses a CRE-regulated reporter gene. Instead of compromised CRE-dependent transcription in HD mice, we found a robust upregulation of CRE-dependent transcription in several brain regions (striatum, hippocampus, cortex). CRE-mediated transcription was also evoked by striatal forskolin infusion and by photic stimulation in HD animals. Increased cAMP response element-binding protein (CREB) phosphorylation and elevated levels of the CREB-regulated gene product, CCAAT/enhancer binding protein β, were also found in HD mice. Significant alterations in CREB binding protein expression and localization were not observed in symptomatic R6/2 mice. Thus, rather than repressing CRE-mediated transcription, mutant huntingtin appears to facilitate transcription via a CRE-dependent mechanismin vivo.
Molecular Basis of Gap Junctional Communication in the CNS of the LeechHirudo medicinalis
Authors: Dykes Iain M. , Freeman Fiona M. , Bacon Jonathan P. , Davies Jane A.
Published: January 2004

Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leechHirudo medicinalis. These innexins show a differential expression in the leech CNS:Hm-inx1is expressed by every neuron in the CNS but not in glia, whereasHm-inx2is expressed in glia but not neurons. Heterologous expression in the pairedXenopusoocyte system demonstrated that both innexins are able to form functional homotypic gap junctions.Hm-inx1forms channels that are not strongly gated. In contrast,Hm-inx2forms channels that are highly voltage-dependent; these channels demonstrate properties resembling those of a double rectifier. In addition,Hm-inx1andHm-inx2are able to cooperate to form heterotypic gap junctions inXenopusoocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two.

This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade.
Endogenous Activation of mGlu5 Metabotropic Glutamate Receptors Contributes to the Development of Nigro-Striatal Damage Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice
Authors: Battaglia Giuseppe , Busceti Carla L. , Molinaro Gemma , Biagioni Francesca , Storto Marianna , Fornai Francesco , Nicoletti Ferdinando , Bruno Valeria
Published: January 2004

We combined the use of knock-out mice and subtype-selective antagonists [2-methyl-6-(phenylethynyl)pyridine (MPEP) and (E)-2-methyl-6-(2-phenylethenyl)-pyridine (SIB1893)] to examine whether endogenous activation of mGlu5 metabotropic glutamate receptors contributes to the pathophysiology of nigro-striatal damage in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. High doses of MPTP (four injections of 20 mg/kg, i.p., every 2 hr) induced a high mortality rate and a nearly total degeneration of the nigro-striatal pathway in wild-type mice. mGlu5 knock-out mice were less sensitive to MPTP toxicity, as shown by a higher survival and a milder nigro-striatal damage. Protection against MPTP (80 mg/kg) toxicity was also observed after MPEP injections (four injections of 5 mg/kg, i.p., 30 min before each MPTP injection). MPEP treatment did not further increase neuroprotection against 80 mg/kg of MPTP in mGlu5 knock-out mice, indicating that the drug acted by inhibiting mGlu5 receptors. In wild-type mice, MPEP was also neuroprotective when challenged against lower doses of MPTP (either 30 mg/kg, single injection, or four of 10 mg/kg injections). The action of MPEP was mimicked by SIB1893 but not by the mGlu1 receptor antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester. MPEP did not change the kinetics of 1-methyl-4-phenylpyridinium ion formation in the striatum of mice injected with MPTP. We conclude that mGlu5 receptors act as amplifiers of MPTP toxicity and that mGlu5 receptor antagonists may limit the extent of nigro-striatal damage in experimental models of parkinsonism.
Inhibition of N-Type Voltage-Activated Calcium Channels in Rat Dorsal Root Ganglion Neurons by P2Y Receptors Is a Possible Mechanism of ADP-Induced Analgesia
Authors: Gerevich Zoltan , Borvendeg Sebestyen J. , Schröder Wolfgang , Franke Heike , Wirkner Kerstin , Nörenberg Wolfgang , Fürst Susanna , Gillen Clemens , Illes Peter
Published: January 2004

Patch-clamp recordings from small-diameter rat dorsal root ganglion (DRG) neurons maintained in culture demonstrated preferential inhibition by ATP of high-voltage-activated, but not low-voltage-activated, Ca2+currents (ICa). The rank order of agonist potency was UTP > ADP > ATP. ATP depressed the ω-conotoxin GVIA-sensitive N-type current only. Pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) and 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate tetraammonium, two P2Y1receptor antagonists, almost abolished the ATP-induced inhibition. Both patch-clamp recordings and immunocytochemistry coupled with confocal laser microscopy indicated a colocalization of functional P2X3and P2Y1receptors on the same DRG neurons. Because the effect of ATP was inhibited by intracellular guanosine 5′-O-(2-thiodiphosphate) or by applying a strongly depolarizing prepulse, P2Y1receptors appear to blockICaby a pathway involving the βγ subunit of a Gq/11protein. Less efficient buffering of the intracellular Ca2+concentration ([Ca2+]i) by reducing the intrapipette EGTA failed to interfere with the ATP effect. Fura-2 microfluorimetry suggested that ATP raised [Ca2+]iby a Gα-mediated release from intracellular pools and simultaneously depressed the high external potassium concentration-induced increase of [Ca2+]iby inhibitingICavia Gβγ. Adenosine 5′-O-(2-thiodiphosphate) inhibited dorsal root-evoked polysynaptic population EPSPs in the hemisected rat spinal cord and prolonged the nociceptive threshold on intrathecal application in the tail-flick assay. These effects were not antagonized by PPADS. Hence, P2Y receptor activation by ADP, which is generated by enzymatic degradation of ATP, may decrease the release of glutamate from DRG terminals in the spinal cord and thereby partly counterbalance the algogenic effect of ATP.
Shrinkage of the Entorhinal Cortex over Five Years Predicts Memory Performance in Healthy Adults
Authors: Rodrigue Karen M. , Raz Naftali
Published: January 2004

Lesions in the hippocampus (HC), the entorhinal cortex (EC), and the prefrontal cortex (PFC) are associated with impairment of episodic memory; reduced HC volume is linked to memory declines in dementia; and decline in EC volume predicts progression from mild cognitive impairment to dementia. However, in healthy adults, the relationship between memory and regional volumes is unclear, and no data are available on the relationship of longitudinal regional shrinkage to memory performance in a cognitively intact population. The objective of this study was to examine whether shrinkage of the EC, HC, and PFC over a 5 year period can predict declarative memory performance in healthy adults. The volumes of three brain regions were measured on magnetic resonance images that were acquired twice, 5 years apart. Multiple measures of episodic memory were administered at follow-up. Results indicated that the volume of HC and PFC (but not EC) correlated with age at baseline and follow-up. However, after age differences in memory were taken into account, none of the regional volumes was associated with memory performance at follow-up. In contrast, greater annual rate of shrinkage in EC (but not HC or PFC) predicted poorer memory performance. Thus, in a healthy and educated population, even mild age-related shrinkage of the EC may be a sensitive predictor of memory decline.
Dopamine Neurons Mediate a Fast Excitatory Signal via Their Glutamatergic Synapses
Authors: Chuhma Nao , Zhang Hui , Masson Justine , Zhuang Xiaoxi , Sulzer David , Hen René , Rayport Stephen
Published: January 2004

Dopamine neurons are thought to convey a fast, incentive salience signal, faster than can be mediated by dopamine. A resolution of this paradox may be that midbrain dopamine neurons exert fast excitatory actions. Using transgenic mice with fluorescent dopamine neurons, in which the axonal projections of the neurons are visible, we made horizontal brain slices encompassing the mesoaccumbens dopamine projection. Focal extracellular stimulation of dopamine neurons in the ventral tegmental area evoked dopamine release and early monosynaptic and late polysynaptic excitatory responses in postsynaptic nucleus accumbens neurons. Local superfusion of the ventral tegmental area with glutamate, which should activate dopamine neurons selectively, produced an increase in excitatory synaptic events. Local superfusion of the ventral tegmental area with the D2 agonist quinpirole, which should increase the threshold for dopamine neuron activation, inhibited the early response. So dopamine neurons make glutamatergic synaptic connections to accumbens neurons. We propose that dopamine neuron glutamatergic transmission may be the initial component of the incentive salience signal.
The Activation Mechanism of α1 Homomeric Glycine Receptors
Authors: Beato Marco , Groot-Kormelink Paul J. , Colquhoun David , Sivilotti Lucia G.
Published: January 2004

The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant α1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10–1000 μm). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open–shut correlation, and single-channelPopendose–response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer.
Cyclin-Dependent Kinase 5 Phosphorylates the N-Terminal Domain of the Postsynaptic Density Protein PSD-95 in Neurons
Authors: Morabito Maria A. , Sheng Morgan , Tsai Li-Huei
Published: January 2004

PSD-95 (postsynaptic density 95) is a postsynaptic scaffolding protein that links NMDA receptors to the cytoskeleton and signaling molecules. The N-terminal domain of PSD-95 is involved in the synaptic targeting and clustering of PSD-95 and in the clustering of NMDA receptors at synapses. The N-terminal domain of PSD-95 contains three consensus phosphorylation sites for cyclin-dependent kinase 5 (cdk5), a proline-directed serine-threonine kinase essential for brain development and implicated in synaptic plasticity, dopamine signaling, cocaine addiction, and neurodegenerative disorders.

We report that PSD-95 is phosphorylated in the N-terminal domain by cdk5in vitroandin vivo, and that this phosphorylation is not detectable in brain lysates of cdk5–/– mice. N-terminal phosphorylated PSD-95 is found in PSD fractions together with cdk5 and its activator, p35, suggesting a role for phosphorylated PSD-95 at synapses. In heterologous cells, coexpression of active cdk5 reduces the ability of PSD-95 to multimerize and to cluster neuronal ion channels, two functions attributed to the N-terminal domain of PSD-95. Consistent with these observations, the lack of cdk5 activity in cultured neurons results in larger clusters of PSD-95. In cdk5–/– cortical neurons, more prominent PSD-95 immunostained clusters are observed than in wild-type neurons. In hippocampal neurons, the expression of DNcdk5 (inactive form of cdk5) or of the triple alanine mutant (T19A, S25A, S35A) full-length PSD-95 results in increased PSD-95 cluster size.

These results identify cdk5-dependent phosphorylation of the N-terminal domain of PSD-95 as a novel mechanism for regulating the clustering of PSD-95. Moreover, these observations support the possibility that cdk5-dependent phosphorylation of PSD-95 dynamically regulates the clustering of PSD-95/NMDA receptors at synapses, thus providing a possible mechanism for rapid changes in density and/or number of receptor at synapses.
Repulsive Guidance Molecule (RGM) Gene Function Is Required for Neural Tube Closure But Not Retinal Topography in the Mouse Visual System
Authors: Niederkofler Vera , Salie Rishard , Sigrist Markus , Arber Silvia
Published: January 2004

The establishment of topographic projections in the developing visual system depends on the spatially and temporally controlled expression of axon guidance molecules. In the developing chick tectum, the graded expression of the repulsive guidance molecule (RGM) has been proposed to be involved in controlling the topography of the retinal ganglion cell (RGC) axon termination zones along the anteroposterior axis of the tectum. We now show that there are three mouse proteins homologous to chick RGM displaying similar proteolytic processing but exhibiting differential cell-surface targeting by glycosyl phosphatidylinositol anchor addition. Two members of this gene family (mRGMaandmRGMb) are expressed in complementary patterns in the nervous system, andmRGMais expressed prominently in the superior colliculus at the time of anteroposterior targeting of RGC axons. The third member of the family (mRGMc) is expressed almost exclusively in skeletal muscles. Functional studies in the mouse reveal a role formRGMain controlling cephalic neural tube closure, thus defining an unexpected role formRGMain early embryonic development. In contrast,mRGMamutant mice did not exhibit defects in anteroposterior targeting of RGC axons to their stereotypic termination zones in the superior colliculus.
Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-β Peptide in Mouse Brain
Authors: Iwata Nobuhisa , Mizukami Hiroaki , Shirotani Keiro , Takaki Yoshie , Muramatsu Shin-ichi , Lu Bao , Gerard Norma P. , Gerard Craig , Ozawa Keiya , Saido Takaomi C.
Published: January 2004

A local increase in amyloid-β peptide (Aβ) is closely associated with synaptic dysfunction in the brain in Alzheimer's disease. Here, we report on the catabolic mechanism of Aβ at the presynaptic sites. Neprilysin, an Aβ-degrading enzyme, expressed by recombinant adeno-associated viral vector-mediated gene transfer, was axonally transported to presynaptic sites through afferent projections of neuronal circuits. This gene transfer abolished the increase in Aβ levels in the hippocampal formations of neprilysin-deficient mice and also reduced the increase in young mutant amyloid precursor protein transgenic mice. In the latter case, Aβ levels in the hippocampal formation contralateral to the vector-injected side were also significantly reduced as a result of transport of neprilysin from the ipsilateral side, and in both sides soluble Aβ was degraded more efficiently than insoluble Aβ. Furthermore, amyloid deposition in aged mutant amyloid precursor protein transgenic mice was remarkably decelerated. Thus, presynaptic neprilysin has been demonstrated to degrade Aβ efficiently and to retard development of amyloid pathology.
Optical Recording of Action Potentials with Second-Harmonic Generation Microscopy
Authors: Dombeck Daniel A. , Blanchard-Desce Mireille , Webb Watt W.
Published: January 2004

Nonlinear microscopy has proven to be essential for neuroscience investigations of thick tissue preparations. However, the optical recording of fast (∼1 msec) cellular electrical activity has never until now been successfully combined with this imaging modality. Through the use of second-harmonic generation microscopy of primaryAplysianeurons in culture labeled with 4-[4-(dihexylamino)phenyl][ethynyl]-1-(4-sulfobutyl)pyridinium (inner salt), we optically recorded action potentials with 0.833 msec temporal and 0.6 μm spatial resolution on soma and neurite membranes. Second-harmonic generation response as a function of change in membrane potential was found to be linear with a signal change of ∼6%/100 mV. The signal-to-noise ratio was ∼1 for single-trace action potential recordings but was readily increased to ∼6–7 with temporal averaging of ∼50 scans. Photodamage was determined to be negligible by observing action potential characteristics, cellular resting potential, and gross cellular morphology during and after laser illumination. High-resolution (micrometer scale) optical recording of membrane potential activity by previous techniques has been limited to imaging depths an order of magnitude less than nonlinear methods. Because second-harmonic generation is capable of imaging up to ∼400 μm deep into intact tissue with submicron resolution and little out-of-focus photodamage or bleaching, its ability to record fast electrical activity should prove valuable to future electrophysiology studies.
Effect of Temperature and Illumination on the Electrical Characteristics of Polymer–Fullerene Bulk‐Heterojunction Solar Cells
Authors: Riedel I. , Parisi J. , Dyakonov V. , Lutsen L. , Vanderzande D. , Hummelen J. C.
Published: January 2004

The current–voltage characteristics of ITO/PEDOT:PSS/OC1C10‐PPV:PCBM/Al solar cells were measured in the temperature range 125–320 K under variable illumination, between 0.03 and 100 mW cm–2 (white light), with the aim of determining the efficiency‐limiting mechanism(s) in these devices, and the temperature and/or illumination range(s) in which these devices demonstrate optimal performance. (ITO: indium tin oxide; PEDOT:PSS: poly(styrene sulfonate)‐doped poly(ethylene dioxythiophene); OC1C10‐PPV: poly[2‐methoxy‐5‐(3,7‐dimethyl octyloxy)‐1,4‐phenylene vinylene]; PCBM: phenyl‐C61 butyric acid methyl ester.) The short‐circuit current density and the fill factor grow monotonically with temperature until 320 K. This is indicative of a thermally activated transport of photogenerated charge carriers, influenced by recombination with shallow traps. A gradual increase of the open‐circuit voltage to 0.91 V was observed upon cooling the devices down to 125 K. This fits the picture in which the open‐circuit voltage is not limited by the work‐function difference of electrode materials used. The overall effect of temperature on solar‐cell parameters results in a positive temperature coefficient of the power conversion efficiency, which is 1.9 % at T = 320 K and 100 mW cm–2 (2.5 % at 0.7 mW cm–2). The almost‐linear variation of the short‐circuit current density with light intensity confirms that the internal recombination losses are predominantly of monomolecular type under short‐circuit conditions. We present evidence that the efficiency of this type of solar cell is limited by a light‐dependent shunt resistance. Furthermore, the electronic transport properties of the absorber materials, e.g., low effective charge‐carrier mobility with a strong temperature dependence, limit the photogenerated current due to a high series resistance, therefore the active layer thickness must be kept low, which results in low absorption for this particular composite absorber.
Synthesis and Properties of a Water‐Soluble Single‐Walled Carbon Nanotube–Poly(m‐aminobenzene sulfonic acid) Graft Copolymer
Authors: Zhao B. , Hu H. , Haddon R. C.
Published: January 2004

Poly(m‐aminobenzene sulfonic acid) (PABS), was covalently bonded to single‐walled carbon nanotubes (SWNTs) to form a water‐soluble nanotube–polymer compound (SWNT–PABS). The conductivity of the SWNT–PABS graft copolymer was about 5.6 × 10–3 S cm–1, which is much higher than that of neat PABS (5.4 × 10–7 S cm–1). The mid‐IR spectrum confirmed the formation of an amide bond between the SWNTs and PABS. The 1H NMR spectrum of SWNT–PABS showed the absence of free PABS, while the UV/VIS/NIR spectrum of SWNT–PABS showed the presence of the interband transitions of the semiconducting SWNTs and an absorption at 17 750 cm–1 due to the PABS addend.
Octupolar Dendrimers with Large First Hyperpolarizability
Authors: Jeong H. C. , Piao M. J. , Lee S. H. , Jeong M.‐Y. , Kang K. M. , Park G. , Jeon S.‐J. , Cho B. R.
Published: January 2004

A series of 1,3,5‐tricyano‐2,4,6‐tris(styryl)benzene derivatives (1,2) and dendrimers (3) have been synthesized and their first hyperpolarizabilities (β) were determined. Whereas the λmax values of 1–3 are similar, the oscillator strength increases with the molecular size. For all compounds, the Stokes shifts are significantly larger when NAr2 is used as the donor. The β(0) values of 1–3 range from 252 to 507 × 10–30 esu and increases with the number of octupolar units in the molecule. When the octupolar molecules are linked to the 1,3,5‐position of the benzene ring by flexible ether linkages, the β(0) value increases by 1.7 fold. On the other hand, octupolar monodendron based on the nitrogen atom core and 1,3,5‐tricyano‐2,4,6‐tris(p‐diarylaminostyryl)benzene moieties at the periphery exhibits β(0) = 507 × 10–30 esu, which is one of the largest β(0) values reported for the octupolar molecules.
Color Tuning in Benzo[1,2,5]thiadiazole‐Based Small Molecules by Amino Conjugation/Deconjugation: Bright Red‐Light‐Emitting Diodes
Authors: Justin Thomas K. R. , Lin J. T. , Velusamy M. , Tao Y.‐T. , Chuen C.‐H.
Published: January 2004

Bipolar compounds (referred to in general as btza) containing a benzo[1,2,5]thiadiazole core and peripheral diarylamines and/or 4‐tert‐butylphenyl moieties have been synthesized via palladium‐catalyzed cross‐coupling reactions of 4,7‐dibromobenzo[1,2,5]thiadiazole with appropriate stannyl compounds. These compounds are fluorescent and the emission color ranges from green to red. The fluorescence of the compounds originates from a charge‐transfer process and exhibits solvatochromism. These red‐light‐emitting materials are amorphous and devices of different configurations were fabricated: I) ITO/btza/TPBI/Mg:Ag; II) ITO/btza/Alq3/Mg:Ag; III) ITO/btza/Mg:Ag (where ITO = indium tin oxide, TPBI = 1,3,5‐tris(N‐phenylbezimidazol‐2‐yl)benzene, and Alq3 = tris(8‐hydroxyquinoline)aluminum). The performance of some of the red‐light‐emitting devices appears to be very promising.
Spreading the Full‐Paper Materials Story
Authors: Grieve K.
Published: January 2004

After three years of publication, Advanced Functional Materials is recognized as a publication of high‐quality in‐depth materials research from around the globe. Find out more about the leading full‐paper materials science journal in this editorial.
Programmable Assembly of Heterogeneous Colloidal Particle Arrays
Authors: Yellen B. B. , Friedman G.
Published: January 2004

Magnetically driven self‐assembly of colloidal particles into highly ordered structures on a substrate is demonstrated. This process allows for programming of specific geometrical patterns of colloidal particles. It also permits assembly of well‐defined colloidal patterns of many different particle types, possibly carrying different labels, e.g., fluorescently labeled beads (see Figure), or different molecular species.
Development of Organic‐Dye‐Doped Silica Nanoparticles in a Reverse Microemulsion
Authors: Zhao X. , Bagwe R. P. , Tan W.
Published: January 2004

A new synthesis method to produce various organic‐dye‐doped silica nanoparticles using a reverse microemulsion has been developed. These nanoparticles show extremely high fluorescent signals (see Figure), excellent photostability, and size uniformity and tenability. These dye‐doped silica nanoparticles can be used for various applications, especially in ultra‐sensitive bioanalysis and in biomedical monitoring.
Colloidal Hydrogel Microlenses
Authors: Serpe M. J. , Kim J. , Lyon L. A.
Published: January 2004

The creation of microlenses from hydrogel microparticles is demonstrated. The fabrication of substrate‐supported microgels is performed using electrostatic interactions between aminopropyltrimethoxysilane‐functionalized glass substrates and acrylic acid groups present on the microgel surface. The lensing ability is illustrated by imaging a photomask through each of the microgels present on the surface (see Figure).