bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of botulinum toxin injection and neurotomy in patients with distal lower limb spasticity
Authors: Rousseaux M. , Buisset N. , Daveluy W. , Kozlowski O. , Blond S. 
Published: March 2008

Background and purpose:  We compared the efficacy of botulinum toxin injection (BTI) and tibial nerve neurotomy (TNN) in an open‐label study of 34 post‐stroke hemiplegic patients with distal lower limb deformation.Methods:  The dose of BT was 300 U (Botox). TNN was performed with a 6–12 month delay on the motor branches of the tibial nerve. Muscles to be treated were selected according to the distal deformity (equinus, varus and clawing toes). Patients were assessed following each treatment for spasticity, motor control, range of movements, balance, gait and the Rivermead Motor Assessment.Results:  TNN (M3, M6 and Y1) resulted in a more significant effect than BTI (D15, M2 and M5) on most of the measures: ankle plantar flexor spasticity, range of movement in dorsiflexion and eversion, foot position in upright situation, Functional Ambulation Categories (barefoot), RMA, gait velocity (comfortable condition), subjective benefit and use of walking aids. Patients treated for tibialis posterior or flexor digitorum longus spasticity often complained of subjective sensory disorders at the plantar sole over a period of 4–6 weeks.Conclusion:  In conclusion, TNN is more effective than BTI on most of the functional parameters. The interest of BTI lies in the preliminary testing of the efficacy of a technique for reducing spasticity on lower limb function.
Life in the fast lane? Towards a sociology of technology and time
Authors: Wajcman Judy 
Published: March 2008

AbstractAssumptions about the pace of life speeding up abound in contemporary social theory. While many factors are contributing to this phenomenon, information and communication technologies are seen as the main drivers. This article considers the way social theorists analyse the concepts of time and speed and then examines how these claims might be assessed in the light of empirical research. Such research shows that time compression has multiple dimensions, and that the effect of digital devices like the mobile phone is not simply one of acceleration. In particular, I suggest that the social studies of technology offers a richer analysis of the reciprocal relationship between technological innovation and changing time practices. My argument is that while the hitherto neglected temporal dimension in sociological theory is now being addressed, there is an urgent need for increased dialogue to connect social theory with detailed empirical studies. Without this, we will continue to have difficulty distinguishing social science from science fiction.
Exploring commonality and difference in in‐depth interviewing: a case‐study of researching British Asian women
Authors: Ramji Hasmita 
Published: March 2008

RetractionThe following article from the British Journal of Sociology entitled ‘Exploring Commonality and Difference in in‐depth interviewing: a case study of researching British‐Asian women’ by Hasmita Ramji, published in 59(1) pp. 99–116, and online on Mar 5 2008 (DOI: 10.1111/j.1468‐4446.2007.00184.x) in Wiley InterScience (http://www.interscience.wiley.com), has been retracted by agreement between the Journal's Editor in Chief, the author, and Blackwell Publishing Ltd. The retraction has been agreed due to substantial overlap between this paper and a paper by Miri Song and David Parker, ‘Commonality, difference and the dynamics of disclosure in in‐depth interviewing’, which appeared in Sociology 29(2), pp. 241–56.
VMAT2 and dopamine neuron loss in a primate model of Parkinson’s disease
Authors: Chen Ming‐Kai , Kuwabara Hiroto , Zhou Yun , Adams Robert J. , Brašić James R. , McGlothan Jennifer L. , Verina Tatyana , Burton Neal C. , Alexander Mohab , Kumar Anil , Wong Dean F. , Guilarte Tomás R. 
Published: March 2008

AbstractWe used positron emission tomography (PET) to measure the earliest change in dopaminergic synapses and glial cell markers in a chronic, low‐dose MPTP non‐human primate model of Parkinson’s disease (PD). In vivo levels of dopamine transporters (DAT), vesicular monoamine transporter‐type 2 (VMAT2), amphetamine‐induced dopamine release (AMPH‐DAR), D2‐dopamine receptors (D2R) and translocator protein 18 kDa (TSPO) were measured longitudinally in the striatum of MPTP‐treated animals. We report an early (2 months) decrease (46%) of striatal VMAT2 in asymptomatic MPTP animals that preceded changes in DAT, D2R, and AMPH‐DAR and was associated with increased TSPO levels indicative of a glial response. Subsequent PET studies showed progressive loss of all pre‐synaptic dopamine markers in the striatum with expression of parkinsonism. However, glial cell activation did not track disease progression. These findings indicate that decreased VMAT2 is a key pathogenic event that precedes nigrostriatal dopamine neuron degeneration. The loss of VMAT2 may result from an association with α‐synuclein aggregation induced by oxidative stress. Disruption of dopamine sequestration by reducing VMAT2 is an early pathogenic event in the dopamine neuron degeneration that occurs in the MPTP non‐human primate model of PD. Genetic or environmental factors that decrease VMAT2 function may be important determinants of PD.
CSF proteomic analysis reveals persistent iron deficiency‐induced alterations in non‐human primate infants
Authors: Geguchadze Ramaz N. , Coe Christopher L. , Lubach Gabriele R. , Clardy Thomas W. , Beard John L. , Connor James R. 
Published: March 2008

AbstractIron deficiency (ID) anemia during infancy results in long‐term neurological consequences, yet the mediating mechanisms remain unclear. Infant monkeys often become naturally anemic during the first 6 months of life, presenting an opportunity to determine the effect of developmental iron deficiency. After weaning, animals were chosen randomly for supplementation with oral iron or, fed a standard commercial chow diet. The control group was never iron deficient. ID anemia was corrected by 12 months in both groups, as indicated by hematological parameters. CSF was collected for proteomic analysis at 12 months of age to assess the impact of developmental ID on the brain. The CSF proteome for both formerly iron deficient groups was similar and revealed 12 proteins with expression levels altered at least twofold. These proteins were identified by matrix assisted laser desorption ionization time‐of‐flight spectrometry and included prostaglandin D synthase, olfactory receptors and glial fibrillary acidic protein. Thus the proteomic analysis reveals a persistent effect of ID and provides insights into reports of disturbed sleep, hypomyelination and other behavioral alterations associated with ID. Furthermore, alterations in the CSF proteome despite normal hematologic parameters indicate that there is a hierarchical system that prioritizes repletion of red cell mass at the expense of the brain.
Inhibitory regulation of glutamate aspartate transporter (GLAST) expression in astrocytes by cadmium‐induced calcium influx
Authors: Liu Yu‐Peng , Yang Chung‐Shi , Tzeng Shun‐Fen 
Published: March 2008

AbstractAfter injury to the CNS, the accumulation of extracellular glutamate induces neuronal excitotoxicity, leading to secondary tissue damage. Astrocytes can reduce excess extracellular glutamate primarily through the astrocytic glutamate transporter‐1 and the Na+‐dependent glutamate/aspartate transporter (GLAST). In this study, we used an in vitro model of cadmium‐induced cellular stress and found that glutamate uptake activity of astrocytes was suppressed because of cadmium‐induced inhibition of GLAST expression. The blockage of cadmium‐triggered Ca2+ influx by Ca2+ chelators elevated GLAST transcription and glutamate uptake activity in astrocytes, suggesting that the suppression of GLAST expression in cadmium‐treated astrocytes was Ca2+‐dependent. This was supported by the findings showing the reduction of GLAST mRNA in astrocytes after treatment with Ca2+‐ionophore A23187. Cadmium reduced human GLAST promoter activity; however, it increased the binding of Ca2+‐sensitive activator protein‐1 (AP‐1) and cAMP response element binding protein (CREB) to their specific elements derived from the human GLAST promoter. These results demonstrate that AP‐1 and CREB may be coupled with Ca2+‐dependent pathway triggered by cadmium to mediate the inhibition of GLAST transcription. Our results suggest that Ca2+ influx into astrocytes after CNS injury could cause the down‐regulation of GLAST expression, thus reducing the astrocytic glutamate uptake function, which in turn may exacerbate secondary damage after CNS injury.
Csk‐homologous kinase interacts with SHPS‐1 and enhances neurite outgrowth of PC12 cells
Authors: Mitsuhashi Hiroaki , Futai Eugene , Sasagawa Noboru , Hayashi Yukiko , Nishino Ichizo , Ishiura Shoichi 
Published: March 2008

AbstractSHPS‐1 is an immunoglobulin superfamily protein with four immunoreceptor tyrosine‐based inhibitory motifs (ITIMs) in its cytoplasmic region. Various neurotrophic factors induce the tyrosine phosphorylation of SHPS‐1 and the association of SHPS‐1 with the protein tyrosine phosphatase SHP‐2. Using a yeast two‐hybrid screen, we identified a protein tyrosine kinase, Csk‐homologous kinase (CHK), as an SHPS‐1‐interacting protein. Immunoprecipitation and pull‐down assays using glutathione S‐transferase (GST) fusion proteins containing the Src homology 2 (SH2) domain of CHK revealed that CHK associates with tyrosine‐phosphorylated SHPS‐1 via its SH2 domain. HIS3 assay in a yeast two‐hybrid system using the tyrosine‐to‐phenylalanine mutants of SHPS‐1 indicated that the first and second ITIMs of SHPS‐1 are required to bind CHK. Over‐expression of wild‐type CHK, but not a kinase‐inactive CHK mutant, enhanced the phosphorylation of SHPS‐1 and its subsequent association with SHP‐2. CHK phosphorylated each of four tyrosines in the cytoplasmic region of SHPS‐1 in vitro. Co‐expression of SHPS‐1 and CHK enhanced neurite outgrowth in PC12 cells. Thus, CHK phosphorylates and associates with SHPS‐1 and is involved in neural differentiation via SHP‐2 activation.
Over‐expression of the catalytic core of mitochondrial DNA (mtDNA) polymerase in the nervous system of Drosophila melanogaster reduces median life span by inducing mtDNA depletion
Authors: Martínez‐Azorín Francisco , Calleja Manuel , Hernández‐Sierra Rosana , Farr Carol L. , Kaguni Laurie S. , Garesse Rafael 
Published: March 2008

AbstractDNA polymerase γ (pol γ) is the sole DNA polymerase devoted to mitochondrial DNA (mtDNA) replication. We have characterized the molecular and physiological effects of over‐expression of the catalytic subunit of pol γ, pol γ‐α, in the nervous system of Drosophila melanogaster using the upstream activation sequence (UAS)/yeast transcriptional activator by binding to UAS (GAL4) system. Tissue‐specific over‐expression of pol γ‐α was confirmed by immunoblot analysis, whereas the very low levels of endogenous protein are undetectable in UAS or GAL4 control lines. The transgenic flies over‐expressing pol γ‐α in the nervous system showed a moderate increase in pupal lethality, and a significant decrease in the median life span of adult flies. Moreover, these flies displayed a decrease in the rate of synthesis of mtDNA, which is accompanied by a significant mtDNA depletion, and a corresponding decrease in the levels of mitochondrial transcription factor A (mtTFA). Biochemical analysis showed an oxidative phosphorylation (OXPHOS) defect in transgenic flies, which were more susceptible to oxidative stress. Although we did not detect apoptosis in the nervous system of adult transgenic flies, brains of larvae over‐expressing pol γ‐α showed evidence of increased cell death that correlates with the observed phenotypes. Our data establish an animal model that mimics some of the features of human mtDNA depletion syndromes.
Complex I specific increase in superoxide formation and respiration rate by PrP‐null mouse brain mitochondria
Authors: Paterson Andrew W. J. , Curtis John C. , MacLeod Nikki K. 
Published: March 2008

AbstractAn imbalance in free radical production and removal is considered by many to be an important factor in the etiology of many degenerative diseases. Since mitochondria are a major source of free radicals, we have examined mitochondrial free radical production in relation to oxidative phosphorylation in PrP‐null mice. Quantitative electron paramagnetic resonance spectroscopy revealed up to a 70% increase in superoxide production from Complex I of submitochondrial particles prepared from PrP‐null mice. This was accompanied by elevated respiratory capacity through Complex I without any discernible alteration in respiratory efficiency. These differences are associated with changes in superoxide dismutase levels and defects in mitochondrial morphology, confirming previously reported results. Our results demonstrate a clear difference in free radical production and oxygen consumption by mitochondrial Complex I between PrP‐null mice and wild‐type controls, pointing to Complex I as a potential target for pathological change, suggesting similarities between prion‐related and other neurodegenerative diseases.
Myosin IIA is required for neurite outgrowth inhibition produced by repulsive guidance molecule
Authors: Kubo Takekazu , Endo Mitsuharu , Hata Katsuhiko , Taniguchi Junko , Kitajo Keiko , Tomura Sayaka , Yamaguchi Atsushi , Mueller Bernhard K. , Yamashita Toshihide 
Published: March 2008

AbstractAlthough myelin‐associated neurite outgrowth inhibitors express their effects through RhoA/Rho‐kinase, the downstream targets of Rho‐kinase remain unknown. We examined the involvement of myosin II, which is one of the downstream targets of Rho‐kinase, by using blebbistatin – a specific myosin II inhibitor – and small interfering RNA targeting two myosin II isoforms, namely, MIIA and MIIB. We found that neurite outgrowth inhibition by repulsive guidance molecule (RGMa) was mediated via myosin II, particularly MIIA, in cerebellar granule neurons. RGMa induced myosin light chain (MLC) phosphorylation by a Rho‐kinase‐dependent mechanism. After spinal cord injury in rats, phosphorylated MLC in axons around the lesion site was up‐regulated, and this effect depends on Rho‐kinase activity. Further, RGMa‐induced F‐actin reduction in growth cones and growth cone collapse were mediated by MIIA. We conclude that Rho‐kinase‐dependent activation of MIIA via MLC phosphorylation induces F‐actin reduction and growth cone collapse and the subsequent neurite retraction/outgrowth inhibition triggered by RGMa.
Accelerated release of exosome‐associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1‐induced amyloid fibril formation
Authors: Yuyama Kohei , Yamamoto Naoki , Yanagisawa Katsuhiko 
Published: March 2008

AbstractExosomes are extracellularly released small vesicles that are derived from multivesicular bodies formed via the endocytic pathway. We treated pheochromocytoma PC12 cells with chloroquine, an acidotropic agent, which potently perturbs membrane trafficking from endosomes to lysosomes. Chloroquine treatment increased the level of GM1 ganglioside in cell media only when the cells were exposed to KCl for depolarization, which is known to enhance exosome release from neurons. In the sucrose‐density‐gradient fractionation of cell media, GM1 ganglioside was exclusively recovered with Alix, a specific marker of exosomes, in the fractions with the density corrresponding to that of exosomes. Notably, amyloid‐β assembly was markedly accelerated when incubated with the exosome fraction prepared from the culture media of PC12 cells treated with chloroquine and KCl. Furthermore, amyloid‐β assembly was significantly suppressed by the co‐incubation with an antibody specific to GM1‐bound amyloid‐β, an endogenous seed for amyloid formation of Alzheimer’s disease. Together with our previous finding that chloroquine treatment induces the accumulation of GM1 ganglioside in early endosomes, results of this study suggest that endocytic pathway abnormality accelerates the release of exosome‐associated GM1 ganglioside following its accumulation in early endosomes. Furthermore, this study also suggests that extracellular amyloid fibril formation is induced by not only GM1 gangliosides accumulated on the surface of the cells but also those released in association with exosomes.
Neurokinin‐3 peptide instead of neurokinin‐1 synergistically exacerbates kainic acid‐inducing degeneration of neurons in the substantia nigra of mice
Authors: Chen Liang‐Wei , Wang Yan‐Qin , Bian Gan‐Lan , Wei Li‐Chun , Yung Kin‐Lam 
Published: March 2008

AbstractNeurokinin peptides neurokinin‐1 (NK1), neurokinin‐3 (NK3), and related receptors are abundantly distributed in the substantia nigra (SN) and evidenced by their possible roles in the Parkinson’s disease. Differential intervention roles of NK3 on kainic acid (KA)‐induced neuronal injury in the SN of mice were thus in vitro and in vivo studied by Fluoro‐Jade C (FJC) staining, immunohistochemistry to tyrosine hydroxylase (TH) or phospho‐NMDA receptor, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. It revealed that (i) in contrast to protective effect of NK1 agonist septide that reduced FJC‐positive degenerative neurons and lesion volume insulted by KA, NK3 agonist senktide significantly increased FJC‐positive ones and lesion volume, and this effect was sufficiently reversed by NK3 antagonist SB218795; (ii) similarly, senktide reduced TH‐positive neurons and this effect was antagonized by SB218795, but septide increased TH‐positive ones; (iii) mechanistic observation showed differential influences of NK1 and NK3 agonists on phosphorylated‐NMDA receptor subunit 1 (phospho‐NMDAR1) and glial fibrillary acidic protein‐expressing astrocytes, i.e. senktide enhanced of NMDA receptor phosphorylation and astrocyte activity, while septide reduced NMDA receptor phosphorylation and astrocytic response; (iv) cell culture further confirmed the exacerbating effect of NK3 agonist on KA‐induced lesion of nigral cells or dopaminergic neurons, in which administration of senktide alone did not show significant cell toxicity. This study presents new evidence that neurokinin NK3 instead of NK1 synergistically exacerbate excitotoxic neuronal degeneration in the SN in a dose‐dependent manner and possibly through modulation of NMDA receptor phosphorylation and astrocyte activity, suggesting their potential significance in novel pharmaceutical therapy against Parkinson’s disease.
Enhanced behavioral sensitivity to the competitive GABA agonist, gaboxadol, in transgenic mice over‐expressing hippocampal extrasynaptic α6β GABAAreceptors
Authors: Saarelainen Kati S. , Ranna Martin , Rabe Holger , Sinkkonen Saku T. , Möykkynen Tommi , Uusi‐Oukari Mikko , Linden Anni‐Maija , Lüddens Hartmut , Korpi Esa R. 
Published: March 2008

AbstractThe behavioral and functional significance of the extrasynaptic inhibitory GABAAreceptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAAreceptor α6 subunit gene in the forebrain under the Thy‐1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)‐type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAAreceptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA‐site competitive agonist gaboxadol (4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol; 3 mg/kg) induced remarkable anxiolytic‐like response in the light : dark exploration and elevated plus‐maze tests in Thy1α6 mice, while being almost inactive in wild‐type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild‐type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAAreceptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAAreceptors revealed that GABA was a partial agonist at α6β3 and α6β3δ receptors, but a full agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAAreceptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.
Novel Brn3a cis‐acting sequences mediate transcription of human trkA in neurons
Authors: Valderrama Ximena , Misra Vikram 
Published: March 2008

AbstracttrkA, the receptor tropomyosin‐related kinase for nerve growth factor, is critical not only for the correct spatial and temporal development of sensory neurons during embryogenesis but also for the survival of sensory neurons, the differentiation and apoptosis of neuronal tumors and suppression of latent herpes simplex virus genomes. While the regulation of the expression of trkA is a complex process, the transcription factor Brn3a is known to play an important role as an enhancer of trkA transcription during development in the mouse. Despite considerable information on the regulation of trkA during embryogenesis, the mechanisms by which the expression of trkA is regulated in differentiated neurons, or the factors that influence its expression in tumor cells, have not been identified. We initiated studies to determine whether Brn3a/trkA promoter interactions may be important in a model of differentiated neurons and in medulloblastoma cells. We constructed a plasmid that contains 1043 base pairs of genomic sequences that extend to 30 nucleotides upstream of trkA coding region. In contrast to previous data, a short 190 bp region that lies proximal to the trkA initiation codon was sufficient for Brn3a responsiveness in Vero cells. This region was also sufficient for Brn3a trans‐activation in nerve growth factor‐differentiated PC12 cells. At least two portions of the 190 bp fragment bind to Brn3a with an affinity high enough to be detected in electromobility shift assays. In addition, Brn3a increased levels of endogenous trkA transcripts in PC12 cells and initiated trkA expression in medulloblastoma cells, which normally do not express trkA.
Gene expression profile of quinacrine‐cured prion‐infected mouse neuronal cells
Authors: Fasano Carlo , Campana Vincenza , Griffiths Beatrice , Kelly Gavin , Schiavo Giampietro , Zurzolo Chiara 
Published: March 2008

AbstractPrion diseases are transmissible fatal neurodegenerative diseases of humans and animals, characterised by the presence of an abnormal isoform (scrapie prion protein; PrPSc) of the endogenous cellular prion protein (PrPC). The pathological mechanisms at the basis of prion diseases remain elusive, although the accumulation of PrPSc has been linked to neurodegeneration. Different genomic approaches have been applied to carry out large‐scale expression analysis in prion‐infected brains and cell lines, in order to define factors potentially involved in pathogenesis. However, the general lack of overlap between the genes found in these studies prompted us to carry an analysis of gene expression using an alternative approach. Specifically, in order to avoid the complexities of shifting gene expression in a heterogeneous cell population, we used a single clone of GT1 cells that was de novo infected with mouse prion‐infected brain homogenate and then treated with quinacrine to clear PrPSc. By comparing the gene expression profiles of about 15 000 genes in quinacrine‐cured and not cured prion‐infected GT1 cells, we investigated the influence of the presence or the absence of PrPSc. By real‐time PCR, we confirmed that the gene encoding for laminin was down‐regulated as a consequence of the elimination of PrPSc by the quinacrine treatment. Thus, we speculate that this protein could be a specific candidate for further analysis of its role in prion infection and pathogenesis.