bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear localization of diacylglycerol kinase ζ in neurons
Authors: Hozumi Yasukazu , Ito Tsukasa , Nakano Tomoyuki , Nakagawa Tamotsu , Aoyagi Masaru , Kondo Hisatake , Goto Kaoru 
Published: September 2003

AbstractDiacylglycerol kinase (DGK) is involved in intracellular signal transduction as a regulator of levels of diacylglycerol which leads to protein kinase C activation. Previous studies have revealed that DGK consists of a family of isozymes in mammalian species and that most if not all of them show abundant expression in the central nervous system, suggesting the importance of this enzyme in neuronal function. Among the isozymes, DGKζ (previously also known as DGK‐IV for the rat clone) has unique structural features, such as four ankyrin‐like repeats and a nuclear localization signal (NLS), and shows intense mRNA expression in neurons of the olfactory bulb, hippocampus and cerebral and cerebellar cortices (Goto, K. & Kondo, H. (1996), Proc. Natl Acad. Sci. USA, 93, 11196–11201). However, previous studies have given conflicting results about whether or not DGKζ localizes to the nucleus in these cells. In this study, we have used immunohistochemistry with specific antibodies in brain tissues and cDNA transfection into primary cultured neurons to address this question. We have shown that, while DGKζ is primarily a nuclear protein in neurons, it can also be cytoplasmic in some conditions, and the subcellular location depends not only on the cell type but also on the developmental state or growth conditions of the cell. In addition, we have used deletion mutants to show that nuclear transport of DGKζ depends on a cooperative interaction between the NLS and the C‐terminal region including ankyrin repeats in a manner which suggests that the NLS is a cryptic site whose exposure is regulated by the C‐terminal region. Together, these results support the hypothesis that the localization of DGKζ may be regulated by differential expression of these various proteins which interact with its C‐terminal region.
Steroidogenic acute regulatory protein in the rat brain: cellular distribution, developmental regulation and overexpression after injury
Authors: Sierra Amanda , Lavaque Esteban , Perez‐Martin Margarita , Azcoitia Iñigo , Hales Dale Buchanan , Garcia‐Segura Luis M. 
Published: September 2003

AbstractThe central nervous system synthesizes steroids which regulate the development and function of neurons and glia and have neuroprotective properties. The first step in this process involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone. This delivery is mediated by steroidogenic acute regulatory protein (StAR). Here, we present a detailed analysis of the distribution of StAR expression in neurons and glia, in the developing, adult and aged male rat brain. Immunohistochemical analysis revealed that StAR is widely distributed throughout the brain, although in each brain area it is restricted to very specific neuronal and astroglial populations. In most regions expressing StAR, immunoreactivity appeared at P10 and the levels of expression then either increased or remained constant until adulthood. In 2‐year‐old rat brains, StAR immunoreactivity was increased compared to young adults. StAR was expressed in the subventricular zone of the adult brain, in proliferating cells which incorporate BrdU as well as in germinal layers in the developing brain. These findings indicate that StAR expression is developmentally regulated and that StAR may play some function in regulating cell proliferation in the brain. Furthermore, StAR mRNA and protein levels were acutely and transiently increased in the hippocampus following excitotoxic brain injury induced by the administration of kainic acid. This raises the possibility that the up‐regulation of StAR expression and the subsequent modifications in steroidogenesis may be part of the mechanisms used by the brain to cope with neurodegeneration.
Expression and activation of caspase 3 following status epilepticus in the rat
Authors: Narkilahti Susanna , Pirttilä Terhi J. , Lukasiuk Katarzyna , Tuunanen Jarkko , Pitkänen Asla 
Published: September 2003

AbstractIt is in dispute whether caspase 3 contributes to status epilepticus (SE)‐induced cell loss. We hypothesized that caspase 3‐mediated cell death continues beyond the acute phase of SE. We induced SE with either kainic acid or electrical stimulation of the amygdala in Wistar and Sprague‐Dawley rats. Caspase 3 immunohistochemistry, Western blot analysis and enzyme activity measurements were used to determine cellular localization and the time course of caspase 3 expression and activation. Immunohistochemistry indicated that caspase 3 protein expression increased following SE, peaking at 16–24 h. Cleavage of procaspase 3 to active fragments (p20–17) was detected 2–7 days after SE. Caspase 3 enzyme activity was elevated at 8 h and further increased up to 19.4‐fold at 7 days following SE. Activation of caspase 3 after SE occurred in the hippocampus and the extrahippocampal temporal lobe but not in the thalamus. Caspase 3‐immunoreactive cells represented only a minority of degenerating cells as assessed by Fluoro‐Jade B and TUNEL staining. Analysis of double‐labelled sections indicated that active caspase 3 was located in astrocytes rather than neurons or microglia. There was increased caspase 3 expression in both rat strains, and it was independent of the method used to induce SE. These data demonstrate that caspase 3 contributes to the cell death occurring within the first week after SE, but in only a small proportion of degenerating cells. These results suggest that, contrary to expectations, caspase 3 inhibitors would have only limited benefits in the treatment of SE.
Analysis of EphB receptors and their ligands in the developing retinocollicular system of the wallaby reveals dynamic patterns of expression in the retina
Authors: Vidovic Maria , Marotte Lauren R. 
Published: September 2003

AbstractThe expression of EphB1 and B2 receptors and ephrins‐B1, ‐B2 and ‐B3 in the retina and superior colliculus of the wallaby (Macropus eugenii) was examined during the development of the retinocollicular projection, using reverse transcription–polymerase chain reaction and immunohistochemistry. There was an early transient differential expression of EphB2 that was higher in ventral retina and restricted to the outer neuroblast layer, whereas a high ventral to low dorsal gradient of ephrin‐B2 expression occurred there throughout the study period. However, there was no dorsoventral gradient of receptors or ligands in retinal ganglion cells or a mediolateral gradient of ephrins in the colliculus. These findings suggest a limited role for these molecules in topographic mapping across the mediolateral colliculus in the wallaby. Early in retinal development there is a complementary pattern of expression of ephrin‐B1 and ‐B2 in the outer neuroblast layer that overlaps with expression of EphB2. Ganglion and amacrine cells also express EphB2. As development proceeds subpopulations of putative horizontal and bipolar cells, also expressing EphB2, come to reside in the inner nuclear layer and ephrin‐B1 is expressed throughout the outer nuclear layer. At the same time cells expressing ephrin‐B2, and subpopulations of horizontal and bipolar cells come to reside in the inner nuclear layer and there is a corresponding decrease in ephrin‐B2 expression in the outer nuclear layer. This pattern of coexpression of receptors and ligands suggests a role for them in cell migration and maintenance of laminar boundaries.
Associative and recognition memory for novel objects in dementia: implications for diagnosis
Authors: Lee Andy C. H. , Rahman Shibley , Hodges John R. , Sahakian Barbara J. , Graham Kim S. 
Published: September 2003

AbstractIt has been demonstrated that patients with dementia of the Alzheimer's type show particular difficulties with a task that measures memory for object locations [R. Swainson et al. (2001) Dement. Geriatr. Cogn. Disord. 12, 265–80]. The present study followed on from this report by asking whether the deficits seen in dementia of the Alzheimer's type were specific to this condition, or whether they would also be seen in another common neurodegenerative syndrome, frontotemporal dementia. To investigate this important issue, we examined memory for object–location pairs and visual recognition memory for novel patterns using two tests, the Paired Associates Learning and Matching to Sample tasks, from the Cambridge Neuropsychological Testing Automated Battery. The performance of a subset of the patients with dementia of the Alzheimer's type described by Swainson et al., selected on the basis of age and education, was compared with matched groups of frontal variant frontotemporal dementia, semantic dementia and control subjects. In contrast to the patients with dementia of the Alzheimer's type, who showed significant impairment on both memory tests, the two frontotemporal dementia groups did not perform significantly poorer compared with control subjects on nearly all memory measures, other than ‘memory score’ from the paired associates learning task. These findings confirm that tests of episodic memory, especially for the location of objects in space, may be useful in the early diagnosis and differentiation of dementia of the Alzheimer's type.
Highly regionalized distribution of stromal cell‐derived factor‐1/CXCL12 in adult rat brain: constitutive expression in cholinergic, dopaminergic and vasopressinergic neurons
Authors: Banisadr Ghazal , Skrzydelski Delphine , Kitabgi Patrick , Rostène William , Parsadaniantz Stéphane Mélik 
Published: September 2003

AbstractThe stromal cell‐derived factor‐1 (SDF‐1)/CXCL12 and its receptor CXCR4 are key modulators of immune functions. In the nervous system, SDF‐1/CXCL12 is crucial for neuronal guidance in developing brain, intercellular communication and the neuropathogenesis of acquired immunodeficiency syndrome. However, cerebral functions of SDF‐1/CXCL12 in adult brain are poorly understood. The understanding of its role in the adult brain needs a detailed neuroanatomical mapping of SDF‐1/CXCL12. By dual immunohistochemistry we demonstrate that this chemokine is constitutively expressed not only in astrocytes and microglia but also in neurons, in discrete neuroanatomical regions. Indeed, neuronal expression of SDF‐1/CXCL12 is mainly found in cerebral cortex, substantia innominata, globus pallidus, hippocampus, paraventricular and supraoptic hypothalamic nuclei, lateral hypothalamus, substantia nigra and oculomotor nuclei. Moreover, we provide the first evidence that SDF‐1/CXCL12 is constitutively expressed in cholinergic neurons in the medial septum and substantia innominata and in dopaminergic neurons in substantia nigra pars compacta and the ventral tegmental area. Interestingly we also show, for the first time, a selective co‐localization of SDF‐1/CXCL12 with vasopressin‐expressing neurons in the supraoptic and paraventricular hypothalamic nuclei. In addition, in the lateral hypothalamic area, SDF‐1/CXCL12 was found to be located on melanin concentrating hormone‐expressing neurons. Altogether, these original data suggest that SDF‐1/CXCL12 could be a modulatory neuropeptide regulating both central cholinergic and dopaminergic systems. In addition, a key role for SDF‐1/CXCL12 in neuroendocrine regulation of vasopressin‐expressing neurons represents an exciting new field of research.
Long‐term Changes in Postnatal Susceptibility to Pilocarpine‐induced Seizures in Rats Exposed to Gamma Radiation at Different Stages of Prenatal Development
Authors: Setkowicz Zuzanna , Kłak Kinga , Janeczko Krzysztof 
Published: September 2003

Summary:  Purpose: To determine whether brains irradiated at different stages of prenatal development also have different postnatal susceptibility to seizures evoked by pilocarpine. Methods: Pregnant Wistar rats were exposed to a single 1.0‐Gy dose of gamma rays on gestation days 13, 15, 17, or 19 (E13, E15, E17, and E19, respectively). On postnatal day 60, their offspring received i.p. pilocarpine injections to evoke status epilepticus. Behavior of the animals was observed continuously for 6 h after the injection, and motor manifestations of seizure activity were rated, and survival times recorded. After 7‐day survival, the animals were killed, and their brains were weighed. Results: The average brain weight of animals exposed to irradiation at earlier prenatal stages (E13 or E15) was significantly lower than that after irradiation on E17 or E19. However, effects of the irradiation on the susceptibility to pilocarpine‐induced seizures were quite opposite. The intensity of status epilepticus evoked in rats irradiated on E13 or E15 was significantly lower than that in nonirradiated controls or in those irradiated on E17 or E19. Moreover, after irradiation on E13 or E15, survival of the animals was significantly higher in relation not only to other irradiated groups but also to the controls. Conclusions: The results suggest than the extent of neuronal deficit, even if relatively greater, cannot always lead to higher susceptibility of the dysplastic brain to seizures. Functional consequences of the deficit, even if its magnitude is relatively smaller but involving specific brain areas, appear to be critical for the epileptogenesis.
Ictal Magnetoencephalography in Temporal and Extratemporal Lobe Epilepsy
Authors: Assaf Bassam A. , Karkar Kameel M. , Laxer Kenneth D. , Garcia Paul A. , Austin Everett J. , Barbaro Nicholas M. , Aminoff Michael J. 
Published: September 2003

Summary:  Purpose: We evaluated visual patterns and source localization of ictal magnetoencephalography (MEG) in patients with intractable temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETE). Methods: We performed spike and seizure recording simultaneously with EEG and MEG on two patients with TLE and five patients with ETE. Scalp EEG was recorded from 21 channels (10‐20 international system), whereas MEG was recorded from two 37‐channel sensors. We compared ictal EEG and MEG onset, frequency, and evolution and performed MEG dipole source localization of interictal spikes and early ictal discharges and co‐registered dipoles to brain magnetic resonance imaging (MRI). We correlated dipole characteristics with intracranial EEG, surgical resection, and outcome. Results: Ictal MEG lateralized seizure onset in both TLE patients and demonstrated ictal onset, frequency, and evolution in accordance with EEG. Ictal MEG source analysis revealed tangential vertical dipoles in the anterolateral angle in one patient, and anterior dipoles with anteroposterior orientation in the other. Intracranial EEG revealed regional entorhinal seizure onset in the first patient. Both patients became seizure free after temporal lobectomy. In ETE, ictal MEG demonstrated visual patterns similar to ictal EEG and had concordant localization with interictal MEG in all five patients. Two patients underwent surgery. Ictal MEG localization was concordant with intracranial EEG in both cases. One patient had successful outcome after surgery. The second patient did not improve after limited resection and multiple subpial transections. Conclusions: Ictal MEG can demonstrate ictal onset frequency and evolution and provide useful localizing information before epilepsy surgery.
Autosomal Dominant Lateral Temporal Epilepsy: Clinical Spectrum, New Epitempin Mutations, and Genetic Heterogeneity in Seven European Families
Authors: Michelucci Roberto , Poza Juan Jose , Sofia Vito , Feo Maria Rita de , Binelli Simona , Bisulli Francesca , Scudellaro Evan , Simionati Barbara , Zimbello Rosanna , D'Orsi Giuseppe , Passarelli Daniela , Avoni Patrizia , Avanzini Giuliano , Tinuper Paolo , Biondi Roberto , Valle Giorgio , Mautner Victor F. , Stephani Ulrich , Tassinari Carlo Alberto , Moschonas Nicholas K. , Siebert Reiner , Munain Adolpho Lopez de , Perez‐Tur Jordi , Nobile Carlo 
Published: September 2003

Summary: Purpose:To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE).Methods:A personal and family history was obtained from each affected and unaffected member, along with a physical and neurologic examination. Routine and sleep EEGs, computed tomography (CT), or magnetic resonance imaging (MRI) were performed in almost all the patients. DNAs from family members were typed with several microsatellite markers localized on either side of LGI1 at 10q24 and screened for LGI1 mutations.Results:  The seven families included a total of 34 affected individuals (10 deceased). The age at onset ranged between 8 and 50 years (average, 22 years). Twenty‐six patients had clear‐cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Less frequent ictal symptoms were visual, psychic, or aphasic seizures, the latter occurring in isolation in one family. The attacks were rare and well controlled by antiepileptic drug treatment but recurred after drug discontinuation. Interictal EEGs were usually unrevealing. MRI or CT scans were negative. Analysis of LGI1/Epitempin exons failed to show mutations in three pedigrees. Linkage analysis strongly suggested exclusion of linkage in one of these families. We found two novel missense mutations, a T→C substitution in exon 6 at position 598, and a T→A transition in exon 8 at position 1295, the latter being detected in a family with aphasic seizures.Conclusions:Our data confirm the inclusion of aphasic seizures within the ADLTE clinical spectrum, suggest the existence of locus heterogeneity in ADLTE, and provide new familial cases with LGI1 missense mutations associated with the disease.
Developmental Outcome of Levetiracetam, Its Major Metabolite in Humans, 2‐Pyrrolidinone N‐Butyric Acid, and Its Enantiomer (R)‐α‐ethyl‐oxo‐pyrrolidine Acetamide in a Mouse Model of Teratogenicity
Authors: Isoherranen Nina , Spiegelstein Ofer , Bialer Meir , Zhang Jing , Merriweather Michelle , Yagen Boris , Roeder Michael , Triplett Aleata A. , Schurig Volker , Finnell Richard H. 
Published: September 2003

Summary:  Purpose: The purpose of this study was to test the teratogenic potential of the antiepileptic drug (AED) levetiracetam (LEV), its major metabolite in humans, 2‐pyrrolidone‐N‐butyric acid (PBA), and enantiomer, (R)‐α‐ethyl‐oxo‐pyrrolidine acetamide (REV), in a well‐established mouse model. Methods: All compounds were administered by intraperitoneal injections once daily to SWV/Fnn mice on gestational days 8½ to 12½. LEV was administered at doses of 600, 1,200, and 2,000 mg/kg/day, piracetam (PIR) and PBA, at 600 and 1,200 mg/kg/day, and REV, at 600 mg/kg/day. On gestational day 18½, fetuses were examined for gross external malformations and prepared for skeletal analysis by using Alizarin Red S staining. Results: No significant gross external malformations were observed in any of the study groups. Fetal weights were significantly reduced in most study groups. Resorption rates were significantly increased only in the 2,000‐mg/kg/day LEV group. The overall incidence of skeletal abnormalities and specifically of hypoplastic phalanges was significantly increased in both PBA treatments and in the intermediate 1,200‐mg/kg/day LEV group. In contrast to that in humans, 24‐h urinary excretion analysis in mice showed that 65–100% of the LEV doses were excreted unchanged, whereas only 4% was excreted as the metabolite PBA. Conclusions: Results of this study demonstrate that both LEV and its major metabolite in humans, PBA, do not induce major structural malformations in developing SWV/Fnn embryos and suggest that they provide a margin of reproductive safety for the pregnant epileptic population when compared with other AEDs tested in this mouse model.
Public finance and the optimal speed of transition*
Authors: Castanheira Micael 
Published: September 2003

AbstractWe develop a general equilibrium model that jointly considers the influence of capital accumulation constraints and of labour market frictions on the process of transition. We endogenize the economic and budgetary costs of different government policies and show that, early in transition, governments ought to subsidize state firms. Provided that intertemporal commitment is feasible, this policy limits the initial output fall, which relaxes capital accumulation constraints, accelerates transition, and increases welfare. Moreover, by resorting to indirect – instead of direct – taxes, governments can bring the path of transition closer to the first best. Yet, political pressures may induce a policy of suboptimal subsidization.
Market integration in Russia during the transformation years*
Authors: Gluschenko Konstantin 
Published: September 2003

AbstractA cross‐sectional relationship among Russian regions between price dispersion and per capita income dispersion is used to measure the degree of integration between regional commodity markets. The sequence of cross‐sectional estimations for each month of the period spanning 1992 through 2000 provides the temporal pattern of market integration in Russia, yielding an integration trajectory. The regional fragmentation of the national market increased during the early years of transition but integration has subsequently tended to improve notwithstanding occasional deviations from this trend.
Does foreign ownership matter?
Authors: Yudaeva Ksenia , Kozlov Konstantin , Melentieva Natalia , Ponomareva Natalia 
Published: September 2003

AbstractThe paper both compares productivity of Russian firms that have foreign direct investments with productivity of fully domestically owned firms and analyses spillovers from foreign‐owned firms to domestic firms. Foreign firms are found to be more productive than domestic ones, but productivity of the former is negatively affected by slow progress of reforms in the regions where they operate. It is also found that there are positive spillovers from foreign‐owned firms to domestic firms in the same industry, but negative effects on domestic firms that are vertically related to foreign‐owned firms. The stock of human capital in regions where foreign firms operate is one of the factors which help domestic firms to benefit from the entry of foreign firms.
Wage arrears uncertainty and precautionary saving in Russia1
Authors: Guariglia Alessandra , Kim Byung‐Yeon 
Published: September 2003

AbstractWage arrears are widespread in Russia, and are one of the main causes of uncertainty in the labour market. In this paper, we use the Russian Longitudinal Monitoring Survey over the period 1994–98 to construct a new and improved measure of household income risk, based on the uncertainty due to wage arrears. We then use this measure of uncertainty to test the precautionary saving hypothesis, according to which households save to self‐insure against risk. We find significant evidence of additional saving by those households whose head is more likely to suffer from wage arrears one year hence. This suggests the existence of a strong precautionary saving motive.
Determinants of household savings in China and their role in quasi‐money supply1
Authors: Qin Duo 
Published: September 2003

AbstractThis study derives household saving potential empirically from econometric models of Chinese urban and rural household consumption and uses this potential to explain household bank deposits. Model simulations are performed to analyse the effects of interest rates, income and income uncertainty on the saving potential and the bank deposits. The bank deposits variable is then used to explain quasi‐money supply. High bank absorption of household savings is found to account mainly for the rapid growth in quasi‐money, which in turn explains the exceptionally highM2/GDP ratio. Households’ savings are largely predictable from their regular consumption.