bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Complete Decomposition of Unemployment Dynamics using Longitudinal Grouped Duration Data*
Authors: Dejemeppe Muriel 
Published: January 2005

AbstractIn this paper, we study the unemployment dynamics in the Belgian regions, Flanders and Wallonia, on the basis of aggregate stratified data covering the period 1973–93. We decompose the aggregate exit probability from unemployment into calendar time and, both observed and unobserved, compositional effects. We find that changes in the inflow composition affect the cyclical fluctuations in unemployment duration only marginally. However, the long‐run improvement in the quality of entrants into unemployment, notably in terms of educational attainment, mitigates the strong upward trend in this duration. This is a new result as none of the existing studies purges the trend in the aggregate outflow rate of the variation in its composition. We also conclude that in Belgium, incidence explains as much as 45% of the evolution of unemployment. Finally, the diverging evolution of unemployment across Flanders and Wallonia predominantly results from a stronger decline in the exit rates from unemployment in Wallonia.
Interpretation of Cointegrating Coefficients in the Cointegrated Vector Autoregressive Model*
Authors: Johansen Søren 
Published: January 2005

AbstractRegression coefficients are interpreted by a counterfactual experiment. For simultaneous equations this experiment can be implemented if the coefficients are identified, and throws some light on the role of instruments and the method of indirect least squares. This paper discusses another counterfactual experiment in the vector autoregressive model in order to interpret the coefficients of an identified cointegrating relation. The dynamics of the model is used to implement a long‐run change by changing the current values. The counterfactual experiment can be conducted precisely when the cointegrating relation is identified.
A Note on the Selection of Time Series Models
Authors: Ng Serena , Perron Pierre 
Published: January 2005

AbstractWe consider issues related to the order of an autoregression selected using information criteria. We study the sensitivity of the estimated order to (i) whether the effective number of observations is held fixed when estimating models of different order, (ii) whether the estimate of the variance is adjusted for degrees of freedom, and (iii) how the penalty for overfitting is defined in relation to the total sample size. Simulations show that the lag length selected by both the Akaike and the Schwarz information criteria are sensitive to these parameters in finite samples. The methods that give the most precise estimates are those that hold the effective sample size fixed across models to be compared. Theoretical considerations reveal that this is indeed necessary for valid model comparisons. Guides to robust model selection are provided.
Bilateral and subcutaneous palmar nodules in a 2‐year‐old child suggesting deep granuloma annulare
Authors: Mur EC , Fernández CM , Hermosa JMH 
Published: January 2005

ABSTRACTGranuloma annulare is a benign, relatively common dermatosis in childhood. The subcutaneous form is rare, and lesions typically occur on the legs, buttocks and scalp. We report a case of a deep granuloma annulare confined to the palms of the hands in a 2‐year‐old child.
Dermal fibrosis and cutaneous necrosis after recombinant interferon‐β1a injection in a multiple sclerosis patient
Authors: Ozden MG , Erel A , Erdem O , Oztas MO 
Published: January 2005

ABSTRACTThe most commonly reported side‐effects of recombinant interferon‐β1a and 1b include local inflammatory injection site reactions, headache, fever, myalgia and a flu‐like syndrome. In this case report, we describe the occurrence of cutaneous necrosis and dermal fibrosis following intramuscular interferon‐β1a injections in a multiple sclerosis patient.
Dyskeratosis follicularis disease: case reports and review of the literature
Authors: Zeglaoui F , Zaraa I , Fazaa B , Houimli S , El Fekih N , Ezzine N , Kamoun MR 
Published: January 2005

ABSTRACTBackground  Dyskeratosis follicularis (Darier's disease) is rare autosomal dominant disease characterized by the loss of adhesion between epidermal cells and by abnormal keratinization.Methods  We performed a retrospective study of all the patients diagnosed with Darier's disease at the Department of Dermatology of Charles Nicolle Hospital of Tunis, between 1971 and 2002.Results  During the observation period, we identified 12 patients with Darier's disease; five males and seven females with a mean age of 17.36 years. No family history was found in eight patients. Skin lesions in the form of keratotic papules were noted in seborrhoeic areas, essentially the face (nine patients), chest and scalp. Seven patients had nail lesions. UV light exposure exacerbated the disease symptoms in seven cases. The patients were treated with topical and systemic retinoids (six cases).Conclusion  Although Darier's disease has a chronic course, most patients manage to lead a relatively normal life. Treatment is usually unsatisfactory despite much progress in understanding of the underlying abnormalities in Darier's disease.
Angioma serpiginosum: report of two unusual cases
Authors: Sandhu K , Gupta S 
Published: January 2005

ABSTRACTAngioma serpiginosum (AS) is a rare vascular naevoid disorder due to ectatic dilation of capillaries in the papillary dermis. The condition is found almost exclusively in females who have grouped erythematous punctate lesions usually on the lower limbs or buttocks. We report two rare cases of AS, each representing a different and unusual clinical feature of AS: one with familial involvement and the other with an extensive distribution of lesions.
Different properties of the central and peripheral forms of human tryptophan hydroxylase
Authors: McKinney Jeffrey , Knappskog Per M. , Haavik Jan 
Published: January 2005

AbstractTryptophan hydroxylase (TPH) catalyses the rate‐limiting reaction in the biosynthesis of serotonin. In humans, two different TPH genes exist, located on chromosomes 11 and 12, respectively, and encoding two enzymes (TPH1 and TPH2) with an overall sequence identity of 71%. We have expressed both enzymes as various fusion proteins in Escherichia coli and using an in vitro transcription/translation system, and compared their solubility and kinetic properties. TPH2 is more soluble than TPH1, has a higher molecular weight and different kinetic properties, including a lower catalytic efficiency towards phenylalanine than TPH1. Both enzymes are phosphorylated by cAMP‐dependent protein kinase A. TPH2 was phosphorylated at Ser19, a phosphorylation site not present in TPH1. The differences between TPH1 and TPH2 have important implications for the regulation of serotonin production in the brain and the periphery and may provide an explanation for some of the diverging results reported for TPH from different sources in the past.
Molecular mechanisms involved in the adenosine A1 and A2A receptor‐induced neuronal differentiation in neuroblastoma cells and striatal primary cultures
Authors: Canals Meritxell , Angulo Ester , Casadó Vicent , Canela Enric I. , Mallol Josefa , Viñals Francesc , Staines William , Tinner Barbro , Joelle Hillion  , Agnati Luigi , Fuxe Kjell , Ferré Sergi , Lluis Carmen , Franco Rafael 
Published: January 2005

AbstractAdenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs) are the major mediators of the neuromodulatory actions of adenosine in the brain. In the striatum A1Rs and A2ARs are mainly co‐localized in the GABAergic striatopallidal neurons. In this paper we show that agonist‐induced stimulation of A1Rs and A2ARs induces neurite outgrowth processes in the human neuroblastoma cell line SH‐SY5Y and also in primary cultures of striatal neuronal precursor cells. The kinetics of adenosine‐mediated neuritogenesis was faster than that triggered by retinoic acid. The triggering of the expression of TrkB neurotrophin receptor and the increase of cell number in the G1 phase by the activation of adenosine receptors suggest that adenosine may participate in early steps of neuronal differentiation. Furthermore, protein kinase C (PKC) and extracellular regulated kinase‐1/2 (ERK‐1/2) are involved in the A1R‐ and A2AR‐mediated effects. Inhibition of protein kinase A (PKA) activity results in a total inhibition of neurite outgrowth induced by A2AR agonists but not by A1R agonists. PKA activation is therefore necessary for A2AR‐mediated neuritogenesis. Co‐stimulation does not lead to synergistic effects thus indicating that the neuritogenic effects of adenosine are mediated by either A1 or A2A receptors depending upon the concentration of the nucleoside. These results are relevant to understand the mechanisms by which adenosine receptors modulate neuronal differentiation and open new perspectives for considering the use of adenosine agonists as therapeutic agents in diseases requiring neuronal repair.
Alzheimer's disease β‐secretase BACE1 is not a neuron‐specific enzyme
Authors: Roßner Steffen , Lange‐Dohna Christine , Zeitschel Ulrike , Perez‐Polo J. Regino 
Published: January 2005

AbstractThe brains of Alzheimer's disease (AD) patients are morphologically characterized by neurofibrillar abnormalities and by parenchymal and cerebrovascular deposits of β‐amyloid peptides. The generation of β‐amyloid peptides by proteolytical processing of the amyloid precursor protein (APP) requires the enzymatic activity of the β‐site APP cleaving enzyme 1 (BACE1). The expression of this enzyme has been localized to the brain, in particular to neurons, indicating that neurons are the major source of β‐amyloid peptides in brain. Astrocytes, on the contrary, are known to be important for β‐amyloid clearance and degradation, for providing trophic support to neurons, and for forming a protective barrier between β‐amyloid deposits and neurons. However, under certain conditions related to chronic stress, the role of astrocytes may not be beneficial. Here we present evidence demonstrating that astrocytes are an alternative source of BACE1 and therefore may contribute to β‐amyloid plaque formation. While resting astroyctes in brain do not express BACE1 at detectable levels, cultured astrocytes display BACE1 promoter activity and express BACE1 mRNA and enzymatically active BACE1 protein. Additionally, in animal models of chronic gliosis and in brains of AD patients, there is BACE1 expression in reactive astrocytes. This would suggest that the mechanism for astrocyte activation plays a role in the development of AD and that therapeutic strategies that target astrocyte activation in brain may be beneficial for the treatment of AD. Also, there are differences in responses to chronic versus acute stress, suggesting that one consequence of chronic stress is an incremental shift to different phenotypic cellular states.
Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Aβ 42/40 ratios
Authors: Walker Emily S. , Martinez Maribel , Brunkan Anne L. , Goate Alison 
Published: January 2005

AbstractGene knockout studies in mice suggest that presenilin 1 (PS1) is the major γ‐secretase and that it contributes disproportionately to amyloid β (Aβ) peptide generation from β‐amyloid precursor protein (APP), whereas PS2 plays a more minor role. Based on this and other observations we hypothesized that familial Alzheimer's disease (FAD) mutations in PS2 would have a dramatic effect on function in order to have an observable effect on Aβ levels in the presence of normal PS1 alleles. Only four of the eight reported FAD mutations in PS2 have altered function in vitro suggesting that the other variants represent rare polymorphisms rather than disease‐causing mutations. In support of our hypothesis, the four verified PS2 FAD mutations cause substantial changes in the Aβ 42/40 ratio, comparable with PS1 mutations that cause very‐early‐onset FAD. Most of the PS2 mutations also cause a significant decrease in Aβ 40, APP C‐terminal fragment (CTF)γ and Notch intracellular domain (NICD) production suggesting that they are partial loss of function mutations. PS2 M239V, its PS1 homolog M233V, and other FAD mutations within transmembrane (TM) 5 of PS1 differentially affect CTFγ and NICD production suggesting that TM5 of PS are important for γ‐secretase cleavage of APP but not Notch.
An RNAi strategy for treatment of amyotrophic lateral sclerosis caused by mutant Cu,Zn superoxide dismutase
Authors: Xia Xu Gang , Zhou Hongxia , Zhou Sili , Yu Yingping , Wu Rui , Xu Zuoshang 
Published: January 2005

AbstractAmyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a neurodegenerative disease characterized by motor neuron degeneration, paralysis and death. One cause of this disease is mutations in the Cu,Zn superoxide dismutase (SOD1) gene. As mutant SOD1 acquires a toxic property that kills motor neurons, by reducing the mutant protein the disease progression may be slowed or prevented. While mutant SOD1 is toxic, the wild‐type SOD1 is indispensable for motor neuron health. Therefore, the ideal therapeutic strategy would be to inhibit selectively the mutant protein expression. Previously we have demonstrated that RNA interference (RNAi) can selectively inhibit some mutant SOD1 expression. However, more than 100 SOD1 mutants can cause ALS and all mutants cannot be inhibited selectively by RNAi. To overcome this obstacle, we have designed a replacement RNAi strategy. Using this strategy, all mutants and wild‐type genes are inhibited by RNAi. The wild‐type SOD1 function is then replaced by designed wild‐type SOD1 genes that are resistant to the RNAi. Here we demonstrate the concept of this strategy.
Thyroid hormone regulates Gαi1 gene expression in the rat cerebellar cortex during post‐natal development
Authors: Alvarez Maria , Perez‐Castillo Ana , Santos Angel 
Published: January 2005

AbstractThyroid hormone regulates the expression of G protein in tissues such as fat and heart. In the brain, very little information is available relative to the regulation by thyroid hormone of G proteins. Here, we show that the expression of the Gαi1 gene is induced by thyroid hormones in the rat cerebellum during development. Hence, the levels of Gαi1 transcripts and protein were decreased in the cerebellum of hypothyroid neonates. In situ hybridization studies showed that the neurons of the cerebellar cortex, particularly Purkinje cells, were affected. Surprisingly, and in contrast with the in vivo stimulatory effect described above, thyroid hormone repressed the activity of the rat Gαi1 promoter in vitro, suggesting that the effect of this hormone in the cerebellum is indirect. In this regard, we present data suggesting that the transcription factor C/EBPβ could be implicated. First, there are active CEBP binding sites in the Gαi1 promoter. Second, we have found a diminished DNA binding activity of hypothyroid nuclear proteins to a Gαi1 promoter sequence containing a C/EBP binding site. Third, this complex is likely to contain C/EBPβ protein as it is displaced by specific anti‐C/EBPβ antibodies. Finally, there is a significant decrease in the C/EBPβ protein content in the hypothyroid cerebellar cortex.
Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment
Authors: Ahmed Naila , Ahmed Usman , Thornalley Paul J. , Hager Klaus , Fleischer Gerd , Münch Gerald 
Published: January 2005

AbstractIncreased damage to proteins by glycation, oxidation and nitration has been implicated in neuronal cell death leading to Alzheimer's disease (AD). Protein glycation, oxidation and nitration adducts are consequently formed. Quantitative screening of these adducts in CSF may provide a biochemical indicator for the diagnosis of AD. To assess this, we measured 11 glycation adducts, three oxidation adducts and a nitration adduct, determining both protein adduct residues and free adducts, in CSF samples of age‐matched normal healthy subjects (n = 18) and subjects with Alzheimer's disease (n = 32). In CSF protein, the concentrations of 3‐nitrotyrosine, Nɛ‐carboxymethyl‐lysine, 3‐deoxyglucosone‐derived hydroimidazolone and N‐formylkynurenine residues were increased in subjects with Alzheimer's disease. In CSF ultrafiltrate, the concentrations of 3‐nitrotyrosine, methylglyoxal‐derived hydroimidazolone and glyoxal‐derived hydroimidazolone free adducts were also increased. The Mini‐Mental State Examination (MMSE) score correlated negatively with 3‐nitrotyrosine residue concentration (p < 0.05), and the negative correlation with fructosyl‐lysine residues just failed to reach significance (p = 0.052). Multiple linear regression gave a regression model of the MMSE score on 3‐nitrotyrosine, fructosyl‐lysine and Nɛ‐carboxyethyl‐lysine residues with p‐values of 0.021, 0.031 and 0.052, respectively. These findings indicate that protein glycation, oxidation and nitration adduct residues and free adducts were increased in the CSF of subjects with Alzheimer's disease. A combination of nitration and glycation adduct estimates of CSF may provide an indicator for the diagnosis of Alzheimer's disease.
Involvement of 3′,5′‐cyclic adenosine monophosphate‐dependent protein kinase in regulation of Fos expression and tyrosine hydroxylase levels during morphine withdrawal in the hypothalamic paraventricular nucleus and medulla oblongata catecholaminergic cell groups
Authors: Benavides Marta , Laorden M. Luisa , Milanés M. Victoria 
Published: January 2005

AbstractMorphine withdrawal stimulates the hypothalamic‐pituitary‐adrenocortical axis activity by activation of nucleus tractus solitarius (NTS)/ventrolateral medulla (VLM) noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN). We investigated whether cAMP‐dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibition of PKA on Fos protein expression and tyrosine hydroxylase (TH) immunoreactivity levels in the PVN and NTS/VLM during morphine withdrawal. Dependence on morphine was induced by a 7‐day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg s.c.). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity levels was observed 90 min after naloxone administration in the PVN and NTS/VLM areas. Morphine withdrawal induced expression of Fos in the PVN and NTS/VLM, indicating an activation of neurones in those nuclei. TH immunoreactivity in NTS/VLM was increased 90 min after induction of morphine withdrawal, whereas there was a decrease in TH levels in the PVN at the same time point. When the selective PKA inhibitor HA‐1004 was infused it greatly diminished the Fos expression observed in morphine‐withdrawn rats. Furthermore, the changes in TH immunoreactivity were significantly modified by infusion of HA‐1004. The present findings suggest that an up‐regulated PKA‐dependent transduction pathway might contribute to the activation of the hypothalamic‐pituitary‐adrenocortical axis in response to morphine withdrawal.
Stimulation of the locus coeruleus elicits noradrenaline and dopamine release in the medial prefrontal and parietal cortex
Authors: Devoto Paola , Flore Giovanna , Saba Pierluigi , Fà Mauro , Gessa Gian Luigi 
Published: January 2005

AbstractOur previous studies have suggested that dopamine and noradrenaline may be coreleased from noradrenergic nerve terminals in the cerebral cortex. To further clarify this issue, the effect of electrical stimulation of the locus coeruleus on extracellular noradrenaline, dopamine and DOPAC in the medial prefrontal cortex, parietal cortex and caudate nucleus was analysed by microdialysis in freely moving rats. Stimulation of the locus coeruleus for 20 min with evenly spaced pulses at 1 Hz failed to modify cortical catecholamines and DOPAC levels. Stimulation with bursts of pulses at 12 and 24 Hz increased, in a frequency‐related manner, not only noradrenaline but also dopamine and DOPAC in the two cortices. In both cortices noradrenaline returned to baseline within 20 min of stimulation, irrespective of the stimulation frequency, whereas dopamine returned to normal within 20 and 60 min in the medial prefrontal cortex and within 60 and 80 min in the parietal cortex after 12 and 24 Hz stimulation, respectively. DOPAC remained elevated throughout the experimental period. Phasic stimulation of the locus coeruleus at 12 Hz increased noradrenaline in the caudate nucleus as in the cerebral cortices but was totally ineffective on dopamine and DOPAC. Tetrodotoxin perfusion into the medial prefrontal cortex dramatically reduced noradrenaline and dopamine levels and suppressed the effect of electrical stimulation. These results indicate that electrical stimulation‐induced increase of dopamine is a nerve impulse exocytotic process and suggest that cortical dopamine and noradrenaline may be coreleased from noradrenergic terminals.
Mutagenesis analysis of the serotonin 5‐HT2C receptor and a Caenorhabditis elegans 5‐HT2 homologue: conserved residues of helix 4 and helix 7 contribute to agonist‐dependent activation of 5‐HT2 receptors
Authors: Xie Jinling , Dernovici Serghei , Ribeiro Paula 
Published: January 2005

AbstractAn alignment of serotonin [5‐hydroxytryptamine (5‐HT)] G protein‐coupled receptors identified a lysine at position 4.45 (helix 4) and a small polar residue (serine or cysteine) at 7.45 (helix 7) that occur exclusively in the 5‐HT2 receptor family. Other serotonin receptors have a hydrophobic amino acid, typically a methionine, at 4.45 and an invariant asparagine at 7.45. The functional significance of these class‐specific substitutions was tested by site‐directed mutagenesis of two distantly related 5‐HT2 receptors, Caenorhabditis elegans 5‐HT2ce and rat 5‐HT2C. Residues 4.45 and 7.45 were each mutated to a methionine and asparagine, respectively, or an alanine and the resulting constructs were tested for activity. A K4.45M mutation decreased serotonin‐dependent activity (Emax) of the rat 5‐HT2C receptor by 60% and that of the C. elegans homologue by 40%, as determined by a fluorometric plate‐based calcium assay. The rat mutant also exhibited nearly sixfold higher agonist binding affinity and significantly lower constitutive activity compared with wildtype. Mutagenesis of S7.45 in the C. elegans receptor increased serotonin binding affinity by up to 25‐fold and decreased Emax by up to 65%. The same mutations of the cognate C7.45 in rat 5‐HT2C produced a smaller fourfold change in the affinity for serotonin and decreased agonist efficacy by up to 50%. Substitutions of S/C7.45 did not produce a significant change in the basal activity of either receptor. All mutants tested exhibited levels of receptor expression similar to the corresponding wildtype based on measurements of specific [3H]‐mesulergine binding or flow cytometry analyses. Taken together, these results suggest that K4.45 and S/C7.45 play an important role in the conformational rearrangements leading to agonist‐induced activation of 5‐HT2 receptors.