bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene disruption of p27
Kip1
allows cell proliferation in the postnatal and adult organ of Corti
Authors: Löwenheim Hubert , Furness David N. , Kil Jonathan , Zinn Christoph , Gültig Karina , Fero Matthew L. , Frost Deanna , Gummer Anthony W. , Roberts James M. , Rubel Edwin W. , Hackney Carole M. , Zenner Hans-Peter
Published: July 2002

Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B.,
et al
. (1995)
Science
267, 1024–1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27
Kip1
is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27
Kip1
-gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27
Kip1
-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.
Staphylococcal protein A: Unfolding pathways, unfolded states, and differences between the B and E domains
Authors: Alonso Darwin O. V. , Daggett Valerie
Published: July 2002

We present multiple native and denaturation simulations of the B and E domains of the three-helix bundle protein A, totaling 60 ns. The C-terminal helix (H3) consistently denatures later than either of the other two helices and contains residual helical structure in the denatured state. These results are consistent with experiments suggesting that the isolated H3 fragment is more stable than H1 and H2 and that H3 forms early in folding. Interestingly, the denatured state of the B domain is much more compact than that of the E domain. This sequence-dependent effect on the dimensions of the denatured state and the lack of correlation with structure suggest that the radius of gyration can be a misleading reaction coordinate for unfolding/folding. Various unfolding and refolding events are observed in the denaturation simulations. In some cases, the transitions are facilitated through interactions with other portions of the protein—contact-assisted helix formation. In the native simulations, the E domain is very stable: after 6 ns, the C
α
root-mean-square deviation from the starting structure is less than 1.4 Å. In contrast, the native state of the B domain deviates more and its inter-helical angles fluctuate. In apparent contrast, we note that the B domain is thermodynamically more stable than the E domain. The simulations suggest that the increased stability of the B domain may be due to heightened mobility, and therefore entropy, in the native state and decreased mobility/entropy in the more compact denatured state.
Infusion of α-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease
Authors: Schiffmann R. , Murray G. J. , Treco D. , Daniel P. , Sellos-Moura M. , Myers M. , Quirk J. M. , Zirzow G. C. , Borowski M. , Loveday K. , Anderson T. , Gillespie F. , Oliver K. L. , Jeffries N. O. , Doo E. , Liang T. J. , Kreps C. , Gunter K. , Frei K. , Crutchfield K. , Selden R. F. , Brady R. O.
Published: July 2002

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). This enzymatic defect results in the accumulation of the glycosphingolipid globotriaosylceramide (Gb
3
; also referred to as ceramidetrihexoside) throughout the body. To investigate the effects of purified α-gal A, 10 patients with Fabry disease received a single i.v. infusion of one of five escalating dose levels of the enzyme. The objectives of this study were: (
i
) to evaluate the safety of administered α-gal A, (
ii
) to assess the pharmacokinetics of i.v.-administered α-gal A in plasma and liver, and (
iii
) to determine the effect of this replacement enzyme on hepatic, urine sediment and plasma concentrations of Gb
3
. α-Gal A infusions were well tolerated in all patients. Immunohistochemical staining of liver tissue approximately 2 days after enzyme infusion identified α-gal A in several cell types, including sinusoidal endothelial cells, Kupffer cells, and hepatocytes, suggesting diffuse uptake via the mannose 6-phosphate receptor. The tissue half-life in the liver was greater than 24 hr. After the single dose of α-gal A, nine of the 10 patients had significantly reduced Gb
3
levels both in the liver and shed renal tubular epithelial cells in the urine sediment. These data demonstrate that single infusions of α-gal A prepared from transfected human fibroblasts are both safe and biochemically active in patients with Fabry disease. The degree of substrate reduction seen in the study is potentially clinically significant in view of the fact that Gb
3
burden in Fabry patients increases gradually over decades. Taken together, these results suggest that enzyme replacement is likely to be an effective therapy for patients with this metabolic disorder.
Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates
Authors: Habib Kamal E. , Weld Katherine P. , Rice Kenner C. , Pushkas Judy , Champoux Maribeth , Listwak Samuel , Webster Elizabeth L. , Atkinson Arthur J. , Schulkin Jay , Contoreggi Carlo , Chrousos George P. , McCann Samuel M. , Suomi Stephen J. , Higley J. Dee , Gold Philip W.
Published: July 2002

We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose-response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity.
Ethionamide activation and sensitivity in multidrug-resistant
Mycobacterium tuberculosis
Authors: DeBarber Andrea E. , Mdluli Khisimuzi , Bosman Marlein , Bekker Linda-Gail , Barry Clifton E.
Published: July 2002

Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of
Mycobacterium tuberculosis
(MTb) have allowed us to demonstrate that ETA is activated by
S
-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [
14
C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide.
A role for Timeless in epithelial morphogenesis during kidney development
Authors: Li Zhixing , Stuart Robert O. , Qiao Jizeng , Pavlova Anna , Bush Kevin T. , Pohl Martin , Sakurai Hiroyuki , Nigam Sanjay K.
Published: July 2002

Central to the process of epithelial organogenesis is branching morphogenesis into tubules and ducts. In the kidney, this can be modeled by a very simple system consisting of isolated ureteric bud (UB) cells, which undergo branching morphogenesis in response to soluble factors present in the conditioned medium of a metanephric mesenchyme cell line. By employing a targeted screen to identify transcription factors involved early in the morphogenetic program leading to UB branching, we identified the mammalian ortholog of Timeless (mTim) as a potential immediate early gene (IEG) important in this process. In the embryo, mTim was found to be expressed in patterns very suggestive of a role in epithelial organogenesis with high levels of expression in the developing lung, liver, and kidney, as well as neuroepithelium. In the embryonic kidney, the expression of mTim was maximal in regions of active UB branching, and a shift from the large isoform of mTim to a smaller isoform occurred as the kidney developed. Selective down-regulation of mTim resulted in profound inhibition of embryonic kidney growth and UB morphogenesis in organ culture. A direct effect on the branching UB was supported by the observation that down-regulation of mTim in the isolated UB (cultured in the absence of mesenchyme) resulted in marked inhibition of morphogenesis, suggesting a key role for Tim in the epithelial cell morphogenetic pathway leading to the formation of branching tubules.
Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling
Authors: Angelastro James M. , Klimaschewski Lars , Tang Song , Vitolo Ottavio V. , Weissman Tamily A. , Donlin Laura T. , Shelanski Michael L. , Greene Lloyd A.
Published: July 2002

Neurotrophic factors such as nerve growth factor (NGF) promote a wide variety of responses in neurons, including differentiation, survival, plasticity, and repair. Such actions often require changes in gene expression. To identify the regulated genes and thereby to more fully understand the NGF mechanism, we carried out serial analysis of gene expression (SAGE) profiling of transcripts derived from rat PC12 cells before and after NGF-promoted neuronal differentiation. Multiple criteria supported the reliability of the profile. Approximately 157,000 SAGE tags were analyzed, representing at least 21,000 unique transcripts. Of these, nearly 800 were regulated by 6-fold or more in response to NGF. Approximately 150 of the regulated transcripts have been matched to named genes, the majority of which were not previously known to be NGF-responsive. Functional categorization of the regulated genes provides insight into the complex, integrated mechanism by which NGF promotes its multiple actions. It is anticipated that as genomic sequence information accrues the data derived here will continue to provide information about neurotrophic factor mechanisms.
Molecular cloning of a 10-deacetylbaccatin III-10-O-acetyl transferase cDNA fromTaxusand functional expression inEscherichia coli
Authors: Walker Kevin , Croteau Rodney
Published: July 2002

The cDNA clone for a 10-deacetylbaccatin III-10-O-acetyl transferase, which catalyzes formation of the last diterpene intermediate in the Taxol biosynthetic pathway, has been isolated fromTaxus cuspidata. By using consensus sequences from an assembly of transacylases of plant origin and from many deduced proteins of unknown function, a homology-based PCR cloning strategy was employed to amplify initially a 911-bp gene fragment of the putative taxane C-10 hydroxyl acetyl transferase fromTaxus. This amplicon was used to screen a cDNA library constructed from mRNA isolated from methyl jasmonate-inducedTaxuscells, from which the full-length 10-deacetylbaccatin III-10-O-transacetylase sequence was obtained. Expression of the ORF from pCWori+inEscherichia coliJM109 afforded a functional enzyme, as determined by1H-NMR and MS verification of the product baccatin III derived from 10-deacetylbaccatin III and acetyl CoA. The full-length cDNA has an ORF of 1,320 bp corresponding to a deduced protein of 440 residues with a calculated molecular weight of 49,052, consistent with the size of the operationally soluble, monomeric, native acetyl transferase. The recombinant acetyl transferase has a pH optimum of 7.5, hasKmvalues of 10 μM and 8 μM for 10-deacetylbaccatin III and acetyl CoA, respectively, and is apparently regiospecific toward the 10-hydroxyl group of the taxane ring. Amino acid sequence comparison of 10-deacetylbaccatin III-10-O-acetyl transferase with taxadienol-5-O-acetyl transferase and with other known acyl transferases of plant origin indicates a significant degree of similarity between these enzymes (80% and 64–67%, respectively).
Plasmid copy-number control and better-than-random segregation genes of pSM19035 share a common regulator
Authors: de la Hoz Ana B. , Ayora Silvia , Sitkiewicz Izabela , Fernández Silvia , Pankiewicz Renata , Alonso Juan C. , Ceglowski Piotr
Published: July 2002

Transcription initiation of the copy-number control and better-than-random segregation genes of the broad-host-range and low-copy-number plasmid pSM19035 are subjected to repression by the autoregulated pSM19035-encoded ω product in
Bacillus subtilis
cells. The promoters of the
copS
(
P
cop1 and
P
cop2), δ (
P
δ), and ω (
P
ω) genes have been mapped. These promoters are embedded in a set of either seven copies of a 7-bp direct repeat or in a block consisting of two 7-bp direct repeats and one 7-bp inverted repeat; the blocks are present either two or three times. The cooperative binding of ω protein to the repeats on the
P
cop1,
P
cop2,
P
δ, and
P
ω promoters represses transcription initiation by a mechanism that does not exclude σ
A
RNAP from the promoters. These results indicate that ω protein regulates plasmid maintenance by controlling the copy number on the one hand and by regulating the amount of proteins required for better-than-random segregation on the other hand.
Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system
Authors: Chong Miriam J. , Murray Michael R. , Gosink Eric C. , Russell Helen R. C. , Srinivasan Anu , Kapsetaki Manuela , Korsmeyer Stanley J. , McKinnon Peter J.
Published: July 2002

Ataxia-telangiectasia is a hereditary multisystemic disease resulting from mutations of ataxia telangiectasia, mutated (
ATM
) and is characterized by neurodegeneration, cancer, immune defects, and hypersensitivity to ionizing radiation. The molecular details of ATM function in the nervous system are unclear, although the neurological lesion in ataxia-telangiectasia becomes apparent early in life, suggesting a developmental origin. The central nervous system (CNS) of Atm-null mice shows a pronounced defect in apoptosis induced by genotoxic stress, suggesting ATM functions to eliminate neurons with excessive genomic damage. Here, we report that the death effector Bax is required for a large proportion of Atm-dependent apoptosis in the developing CNS after ionizing radiation (IR). Although many of the same regions of the CNS in both
Bax
−/− and
Atm
−/− mice were radioresistant, mice nullizygous for both
Bax
and
Atm
showed additional reduction in IR-induced apoptosis in the CNS. Therefore, although the major IR-induced apoptotic pathway in the CNS requires Atm and Bax, a p53-dependent collateral pathway exists that has both Atm- and Bax-independent branches. Further, Atm- and Bax-dependent apoptosis in the CNS also required caspase-3 activation. These data implicate Bax and caspase-3 as death effectors in neurodegenerative pathways.
How important are entropic contributions to enzyme catalysis?
Authors: Villà J. , Štrajbl M. , Glennon T. M. , Sham Y. Y. , Chu Z. T. , Warshel A.
Published: July 2002

The idea that enzymes accelerate their reactions by entropic
effects has played a major role in many prominent proposals about the
origin of enzyme catalysis. This idea implies that the binding to an
enzyme active site freezes the motion of the reacting fragments and
eliminates their entropic contributions,
(Δ
S
cat
‡
)′, to the
activation energy. It is also implied that the binding entropy is equal
to the activation entropy,
(Δ
S
w
‡
)′, of the
corresponding solution reaction. It is, however, difficult to examine
this idea by experimental approaches. The present paper defines the
entropic proposal in a rigorous way and develops a computer simulation
approach that determines (Δ
S
‡
)′. This
approach allows us to evaluate the differences between
(Δ
S
‡
)′ of an enzymatic reaction and of the
corresponding reference reaction in solution. Our approach is used in a
study of the entropic contribution to the catalytic reaction of
subtilisin. It is found that this contribution is much smaller than
previously thought. This result is due to the following:
(
i
) Many of the motions that are free in the
reactants state of the reference solution reaction are also free at the
transition state. (
ii
) The binding to the enzyme
does not completely freeze the motion of the reacting fragments so that
(Δ
S
‡
)′ in the enzymes is not zero.
(
iii
) The binding entropy is not necessarily equal
to (Δ
S
w
‡
)′.
Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas
Authors: Aboody Karen S. , Brown Alice , Rainov Nikolai G. , Bower Kate A. , Liu Shaoxiong , Yang Wendy , Small Juan E. , Herrlinger Ulrich , Ourednik Vaclav , Black Peter McL. , Breakefield Xandra O. , Snyder Evan Y.
Published: July 2002

One of the impediments to the treatment of brain tumors (e.g.,
gliomas) has been the degree to which they expand, infiltrate
surrounding tissue, and migrate widely into normal brain, usually
rendering them “elusive” to effective resection, irradiation,
chemotherapy, or gene therapy. We demonstrate that neural stem cells
(NSCs), when implanted into experimental intracranial gliomas
in
vivo
in adult rodents, distribute themselves quickly and
extensively throughout the tumor bed and migrate uniquely in
juxtaposition to widely expanding and aggressively advancing tumor
cells, while continuing to stably express a foreign gene. The NSCs
“surround” the invading tumor border while “chasing down”
infiltrating tumor cells. When implanted intracranially at distant
sites from the tumor (e.g., into normal tissue, into the contralateral
hemisphere, or into the cerebral ventricles), the donor cells migrate
through normal tissue targeting the tumor cells (including human
glioblastomas). When implanted outside the CNS intravascularly, NSCs
will target an intracranial tumor. NSCs can deliver a therapeutically
relevant molecule—cytosine deaminase—such that quantifiable reduction
in tumor burden results. These data suggest the adjunctive use of
inherently migratory NSCs as a delivery vehicle for targeting
therapeutic genes and vectors to refractory, migratory, invasive brain
tumors. More broadly, they suggest that NSC migration can be extensive,
even in the adult brain and along nonstereotypical routes, if pathology
(as modeled here by tumor) is present.
Cracks in the β-can: Fluorescent proteins from
Anemonia sulcata
(Anthozoa, Actinaria)
Authors: Wiedenmann Jörg , Elke Carsten , Spindler Klaus-Dieter , Funke Werner
Published: July 2002

We characterize two green fluorescent proteins (GFPs), an orange
fluorescent protein, and a nonfluorescent red protein isolated from the
sea anemone
Anemonia sulcata
. The orange fluorescent
protein and the red protein seem to represent two different states of
the same protein. Furthermore, we describe the cloning of a GFP and a
nonfluorescent red protein. Both proteins are homologous to the GFP
from
Aequorea victoria
. The red protein is significantly
smaller than other GFP homologues, and the formation of a closed
GFP-like β-can is not possible. Nevertheless, the primary structure
of the red protein carries all features necessary for orange
fluorescence. We discuss a type of β-can that could be formed in a
multimerization process.
Mouse VAP33 is associated with the endoplasmic reticulum and microtubules
Authors: Skehel P. A. , Fabian-Fine R. , Kandel E. R.
Published: July 2002

VAMP/synaptobrevin is a synaptic vesicle protein that is essential for neurotransmitter release. Intracellular injection of antisera against the
Aplysia californica
VAMP/synaptobrevin-binding protein ApVAP33 inhibited evoked excitatory postsynaptic potentials (EPSPs) in cultured cells, suggesting that this association may regulate the function of VAMP/synaptobrevin. We have identified and characterized a mouse homologue of ApVAP33, mVAP33. The overall domain structure of the proteins is conserved, and they have similar biochemical properties. mVAP33 mRNA is detectable in all mouse tissues examined, in contrast to the more restricted expression seen in
A. californica.
We analyzed the cellular distribution of mVAP33 protein in brain slices and cultured cortical cells by light and electron microscopy. Although present at higher levels in neurons, immunoreactivity was detected throughout both neurons and glia in a reticular pattern similar to that of endoplasmic reticulum-resident proteins. mVAP33 does not colocalize with VAMP/synaptobrevin at synaptic structures, but expression overlaps with lower levels of VAMP/synaptobrevin in the soma. Ultrastructural analysis revealed mVAP33 associated with microtubules and intracellular vesicles of heterogeneous size. In primary neuronal cultures, large aggregates of mVAP33 are also detected in short filamentous structures, which are occasionally associated with intracellular membranes. There is no evidence for accumulation of mVAP33 on synaptic vesicles or at the plasma membrane. These data suggest that mVAP33 is an endoplasmic-reticulum–resident protein that associates with components of the cytoskeleton. Any functional interaction between mVAP33 and VAMP/synaptobrevin, therefore, most likely involves the delivery of components to synaptic terminals rather than a direct participation in synaptic vesicle exocytosis.
Genetic reconstruction of individual colorectal tumor histories
Authors: Tsao Jen-Lan , Yatabe Yasushi , Salovaara Reijo , Järvinen Heikki J. , Mecklin Jukka-Pekka , Aaltonen Lauri A. , Tavaré Simon , Shibata Darryl
Published: July 2002

It is difficult to observe human tumor progression as precursor lesions are systematically removed. Alternatives to direct observations, commonly used to reveal the hidden past of species and populations, are sequence comparisons or molecular clocks. Noncoding microsatellite (MS) loci were employed as molecular tumor clocks in 13 human mutator phenotype (MSI
+
) colorectal tumors. Quantitative analysis revealed that specific patterns of somatic MS mutations accumulate with division after loss of mismatch repair (MMR). Tumors had unique patterns of MS mutation, and, therefore, based on this model, each tumor had its own unique history. Loss of MMR occurred very early relative to terminal clonal expansion, with an estimated average of 2,300 divisions since loss of MMR and 280 divisions since expansion. Contrary to the classical adenoma-cancer sequence, MSI
+
adenomas were nearly as old as cancers (2,000 versus 2,400 divisions since loss of MMR). Negative clinical examinations preceded six tumors, independently documenting an absence of visible precursors during early MSI
+
adenoma or cancer progression. These findings further extend a window beyond visible progression since loss of MMR appears to start a genetic phase involving clone sizes or phenotypes below a threshold of clinical detection. This previously occult prologue before visible neoplasia is longer and therefore likely more important than generally appreciated.
Diabetes-associated mutations in a β-cell transcription factor destabilize an antiparallel “mini-zipper” in a dimerization interface
Authors: Hua Qing-Xin , Zhao Ming , Narayana Narendra , Nakagawa Satoe H. , Jia Wenhua , Weiss Michael A.
Published: July 2002

Maturity-onset diabetes of the young, a monogenic form of Type II diabetes mellitus, is most commonly caused by mutations in hepatic nuclear factor 1α (HNF-1α). Here, the dimerization motif of HNF-1α is shown to form an intermolecular four-helix bundle. One face contains an antiparallel coiled coil whereas the other contains splayed α-helices. The “mini-zipper” is complementary in structure and symmetry to the top surface of a transcriptional coactivator (dimerization cofactor of homeodomains). The bundle is destabilized by a subset of mutations associated with maturity-onset diabetes of the young. Impaired dimerization of a β-cell transcription factor thus provides a molecular mechanism of metabolic deregulation in diabetes mellitus.
Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly
Authors: Murakami Koichi , Fellous Arlette , Baulieu Etienne-Emile , Robel Paul
Published: July 2002

Fetal or adult rat-brain cytosol and fetal rat-brain microtubules contain a high-affinity, low-capacity pregnenolone-binding protein. The equilibrium dissociation constant is in the 30–50 nM range. The best competitors (in decreasing order) are pregnenolone sulfate, progesterone, Δ5-pregnene-3β,20α-diol, and 3β-hydroxy-5α-pregnan-20-one. It was hypothesized that the pregnenolone-binding protein pertained to microtubule-associated proteins (MAPs). Indeed, partial purification of fetal brain cytosol by fast pressure liquid chromatography with sequential ion-exchange and gel-filtration columns yielded two fractions, one of very high molecular mass, >200 kDa, and the other of 40–60 kDa, enriched in [
3
H]pregnenolone-binding activity and in proteins immunolabeled with monoclonal anti-tubulin and anti-MAP2 antibodies. Because many proteins are associated with microtubules, binding assays were repeated with purified calf-brain tubulin, MAP2, and Tau protein. Only the MAP2 fraction showed saturable [
3
H]pregnenolone binding with an affinity very close to that of rat-brain microtubules, but with a much larger concentration of binding sites (16 pmol/mg MAP2), which was increased more than 8-fold after copolymerization of MAP2 with tubulin. Finally, steroid effects on microtubule-assembly kinetics were assayed. Pregnenolone induced a large, dose-related increase of both the rate and extent of MAP2-induced tubulin assembly, whereas progesterone, inactive
per se
, counteracted the stimulatory effect of pregnenolone. Electron microscopic analysis confirmed that pregnenolone-increased assembly of microtubules produced a completely normal structure. The stimulatory effect on MAP2–tubulin interaction was also observed in fetal rat-brain neuron cultures. Therefore, we propose a mechanism of neurosteroid action, the control of microtubule or, more generally, of neural cytoskeleton dynamics, with potential roles in brain development, plasticity, and aging.
Expérience du stress à l'adolescence
Authors: Dumont Michelle
Published: July 2002

Cette étude aborde les relations entre le stress–certains facteurs de protection—la détresse auprès de 297 adolescents québécois. Dans un premier temps, cette étude examine si ces relations different selon le sexe du participant. Dans un second temps, cette recherche prédit l'expérience du stress à l'adolescence (indices de fréquence, d'intensité, de sévérité) à partir de la dépression, de l'estime de soi, du soutien social et de certaines stratégies adaptatives. En contrôlant pour l'âge des participants, les résultats indiquent que les adolescentes se sentent davantage menacées par le stress chronique que les adolescents, sont plus dépressives, rapportent davantage de personnes disponibles dans leur réseau social et adoptent plus souvent des stratégies adaptatives cognitives ou de recherche de soutien social. Elles auraient en revanche une moins bonne estime de soi que les garçons. En ce qui concerne le deuxième objectif de cette étude, soulignons que l'estime de soi et les stratégies adaptatives évitantes prédisent la fréquence et la sévérité du stress à l'adolescence, ceci en contrôlant pour l'âge et le sexe du participant, alors que l'état dépressif est le seul facteur pouvant prédire les trois indices de stress (fréquence, intensité, sévérité), contrairement au soutien social et aux stratégies adaptatives sociales ou cognitives.
Residence Spells and Migration: A Comparison for Men and Women
Authors: Detang-Dessendre Cecile , Molho Ian
Published: July 2002

This paper models migration probabilities in a duration context, where migration may occur at the end of an observed residence spell. The analysis is based on a sample of young women in rural locations in France, and relates to their first move after leaving full-time education. We distinguish between residence spells that end in long- as compared to short-distance moves. The results for women are compared with those in an earlier analysis for men. Single women are found to be significantly less likely than non-single (for example, married) women to move, and this effect is stronger than the corresponding effect for men. Women appear to develop weaker job attachments than men over time, but stronger attachments to their home. Finally, women appear to respond less strongly than men to employment status transitions.
Moving Costs and the Dynamics of Housing Demand
Authors: Nordvik Viggo
Published: July 2002

It is well established that moving costs make households adjust their housing consumption far less frequently than they would have done in a world in which relocation was costless. This paper adds to our understanding of the dynamics of housing demand by constructing a life-cycle model of housing demand on which several numerical experiments are performed. Among other things, it is shown how the sign of price elasticities may be indeterminate because of changes in moving careers induced by price changes. The paper also demonstrates that planned (endogenous) moving activity and stochastic forced moves should be analysed within a common analytical framework. One simple version of such a common analytical framework is presented and discussed.
A Model of Spatial Patterns across Local Retail Property Markets in Great Britain
Authors: Jackson Catherine
Published: July 2002

Property markets are commonly modelled either at relatively high levels of aggregation (such as regional or national) using time-series data or panel data, or at individual-town level. This paper develops a cross-sectional model of a large number of retail property markets at the city and town level. The model is developed using prime retail rental levels data as the dependent variable and a number of demand and supply variables, suggested by theory, as independent variables. The model takes the form of a single equation and is based on multiple linear least-squares regression analysis. During the course of the paper, a number of issues are addressed: principal components analysis is suggested as a method of reducing multicollinearity in a model, and the spatial stability of the model is assessed. The paper concludes that the size of the retail core (as measured by the number of national multiple retailers present) and the demographic profile of the local population provide a highly significant explanation for the differential rental levels across towns and cities in Great Britain. The model generally exhibits a high degree of spatial stability, when tested using dummy variables and F tests. However, there is some evidence of spatial instability in the common model between southern and northern centres, large versus smaller centres and across centres with high, medium or low rental levels, but this is inconclusive.
Attractivity and Internationalisation of Major European Cities: The Example of Air Traffic
Authors: Cattan Nadine
Published: July 2002

Researchers, planners, politicians and journalists wonder about the possibilities of evaluating the international attractivity of European cities. Fashion effects or important issues in this end-of-century, the comparison, the ranking of cities have frequently been written about and have been the object of debate. Beyond the publicised aspect, what answers can be given to determine the international role of European cities? The volumes, the intensity and the degree of concentration of international air traffic, the degree of international air opening and the number of international air routes are the five measures proposed for the evaluation of the international role of 90 large European cities. It is, however, a more complex indicator 'the differential attractivity' that gives the most relevant image of the internationalisation of cities. The research of explanatory factors of the differential attractivity variation allows us to demonstrate that the European urban network remains largely dependent on national urban system configurations.
Urban Hierarchies and Territorial Competition in Europe: Exploring the Role of Fairs and Exhibitions
Authors: Rubalcaba-Bermejo Luis , Cuadrado-Roura Juan R.
Published: July 2002

Cities of Europe tend to be thought of in hierarchical terms. Although interesting results have been achieved, it seems clear that there is no single hierarchy. The process of European integration is generating numerous changes in different fields. One of these changes is the need for European capitals and cities of a certain size to upscale their position from national to continental. A system of European cities competing with one another to attract activities and facilities and to gain international influence is in formation. Fairs and exhibitions are an example. The paper provides a first approach to the role and the economic weight of exhibitions in the EU, trying to sketch out a hierarchy of fair-hosting cities. The most significative variables are analysed, exploring their explanatory power. An interpretative hypothesis linking exhibition size and internationality to inter-urban competition is finally provided.
Changing Sources of Suburban Support for Local Growth Controls
Authors: Baldassare Mark , Wilson Georjeanna
Published: July 2002

Surveys conducted over time in the Orange County, CA, suburban region are used to test hypotheses about the predictors of support for local growth controls. Between 1982 and 1993, public support for local growth controls first increased and then declined. Negative community perceptions are consistently related to support for local growth controls, while higher municipal growth rates are never significant. Higher socio-economic status is related to support for stricter growth controls only at the early stage, while perceived rapid growth is a significant factor at later times. Personal characteristics that have been related to environmentalism (i.e. age, liberalism) become significant predictors of perceiving rapid growth in the latest stage. The changing sources of suburban support for local growth controls help to explain why previous studies taken at one point in time have contradictory findings.
Population Migration, Regional Economic Growth and Income Determination: A Comparative Study of Dongguan and Meizhou, China
Authors: Li Si-Ming
Published: July 2002

Population migration, regional economic growth and income determination in China are all popular research topics. In a country with a vast geographical extent and varied geographical heritage, and with the hukou or household registration system still playing an important part in structuring a person's life-chances, these three variables are closely intertwined. The present study attempts to link the three together. It draws on data from a household survey conducted in the cities of Dongguan and Meizhou, both of Guangdong province. The former has experienced highly rapid economic growth since 1978 because of its proximity to Hong Kong, whereas the latter has suffered from its relative geographical remoteness. A series of covariance tests arranged in a hierarchical manner confirms the hypothesis that a given set of income determinants has different effects in different geographical and migratory-status settings. While income generally has a curvilinear relationship with age, this is not the case for the Meizhou permanent migrants. The effect of education on income, after controlling for occupation and other variables, also shows systematic variations with level of economic development. In Meizhou, where the degree of market penetration is low and where formal credentials are of paramount importance, holding a higher education diploma almost guarantees a higher income, ceteris paribus ; but in Dongguan education only brings about higher income through its effects on occupation type. The temporary migrants who do not possess permanent residential status constitute an obvious disadvantaged group. For this group, discrimination prevails, regardless of the nature of the work unit's ownership type.
The Private Finance Initiative and the Changing Governance of the Built Environment
Authors: Kerr Derek
Published: July 2002

The Private Finance Initiative (PFI), introduced by the British government in 1992, marks a potentially significant change in the form and nature of the production, consumption and management of the built environment and of the services delivered through that built environment. This paper provides an outline of the constitution and development of the PFI, but does so in terms of a conceptual framework that situates the national state form and its policy-making process within the changing nature of the global accumulation of capital. It argues that the PFI is a mode of governance through which the state is attempting to restructure itself and, indirectly, class relations, by transforming the social relations of service and infrastructure provision and subordinating them to the discipline of the market.
Assessing Psychiatric Morbidity from Community Registers: Methods for Bayesian Adjustment
Authors: Congdon Peter , Smith Alan , Dean Christine
Published: July 2002

This paper considers Bayesian approaches to adjusting small area prevalence estimates derived from a community register of the seriously mentally ill, by taking account of underlying variability in latent prevalence between areas. Adjustment of individual prevalence rates to take account of the entire spatial distribution has implications both for epidemiological inference and resource rankings for localities. The more commonly adopted empirical Bayes approaches are here compared with fully Bayes approaches. Fully Bayes methods allow for uncertainty in the prevalence parameters and also permit the inclusion of information from other sources (for example, hospital admissions for mental illness) or from previous studies. The impact of socioeconomic indices on morbidity and its relevance for adjusted prevalence estimates is also considered. A case study is applied to an East London Health Authority, Barking and Havering.
School Segregation: The Case of Amsterdam
Authors: Gramberg Peter
Published: July 2002

This article deals with some facets of school segregation in Amsterdam. As two-thirds of Amsterdam youth have a non-native background nowadays, this has implications for the composition of primary and secondary schools. Segregation in primary education has a lot to do with residential segregation, although the 'colour' of the neighbourhood is intensified at the school level. Segregation in secondary education has mainly to do with the educational level of various population groups and to a lesser extent with residential segregation. Parents, children and headmasters have been interviewed about their behaviour and policy on segregation. It is concluded that in some way they intensify the school segregation.
The Changing Fabrics of Ordinary Residential Areas
Authors: Whitehand J.W.R. , Carr Christine M. H.
Published: July 2002

An increasing proportion of change to the built environments of Western countries consists of adaptations of existing physical forms. Many changes are small-scale and piecemeal, but cumulatively they have a major impact on the physical character of the environment. This paper considers the physical changes that have taken place in one of the most extensive types of area in English cities: the suburbs created by private enterprise between the two world wars. Within each of the two cities studied, Birmingham and London, the form and density of the original development were major factors influencing the distribution of additional dwellings, demolitions and modifications of existing houses, and the types of new dwelling constructed. Between the mid 1950s and the mid 1960s in London, but a few years later in Birmingham, the insertion of additional houses by developers was the main type of change. From the early 1970s, individual householders became major instigators of change to existing houses, especially in London, where incomes rose more rapidly. House extensions were an important element in this change, despite the decline in household size. The large majority of planning applications for changes to existing houses, but only about one-half of those for the construction of additional dwellings, were approved.
Employment Impact of Inner-city Development Projects: The Case of Underground Atlanta
Authors: Hotchkiss Julie L. , Sjoquist David L. , Zobay Stephanie M.
Published: July 2002

This paper makes use of a unique data set to explore the issue of whether inner-city residents are more likely to be hired by a new inner-city development than non-residents. A selection model with partial observability is specified and estimated. This partial observability model allows us to control for self-selection at the application stage and to obtain unconditional estimates at the hiring stage. We determine, holding individual and neighbourhood characteristics constant, that while inner-city residents are less likely to be considered 'hireable', their greater propensity to apply for jobs at this development means that they were at least as likely as non-residents to both apply and be hired. We also tentatively conclude that distance between an applicant's residence and the location of the development does not appear to have been an issue in the application decision.
Fiscal Pressure, Tax Competition and the Adoption of Tax Increment Financing
Authors: Man Joyce Y.
Published: July 2002

Tax increment financing (TIF) has been widely adopted as an economic development tool by municipalities. This study estimates a structural probit model of municipal TIF adoption decisions using data drawn from cities in Indiana. It provides empirical evidence that factors such as fiscal pressures, tax competition, economic distress, industrial composition, availability of alternative programmes and the expected gains in property values from the use of TIF exert significant influence in a city's decision to adopt a TIF programme. After using an accurate measure of prior growth, this analysis finds no empirical evidence to support the contention that growing cities are more likely to adopt TIF.
Improving young children’s free narratives about an observed event: The effects of nonspecific verbal prompts
Authors: Elischberger Holger B. , Roebers Claudia M.
Published: July 2002

The aim of the present study was to evaluate the efficacy of two nonspecific verbal prompts in interviewing preschool children and second graders. Forty kindergartners (M age = 71.6 months) and 46 second graders (M age = 97.6 months) watched a 7 minute video about a gang of adolescent boys stealing money from another youth. Three weeks later they were interviewed about the content of the film under two experimental conditions. Both groups were first asked to report everything that they could remember about the movie. This initial instruction was then repeated twice for the no cues group. Participants in the verbal cues group were instead instructed to report everything they remembered seeing and everything they remembered hearing. In addition, verbal intelligence was measured for all participants. Children of both age groups reported significantly more information when they were interviewed under the verbal cues condition. The use of the verbal prompts did not affect the overall high levels of accuracy. Verbal intelligence showed a moderate positive effect on measures of recall but did not moderate the efficacy of the verbal prompts.
Ecology, childhood experiences, and adult attachment styles of women in the kibbutz
Authors: Sharabany Ruth , Mayseless Ofra , Edri Gilat , Lulav Doron
Published: July 2002

The present study exploited a “natural experiment” which covered variations in child-rearing conditions within the communal setting of the Israeli kibbutz. The long-term effects of these variations and of childhood experiences on attachment styles of adults were examined. Three groups of mothers who were raised in the kibbutz participated: (1) a Communal group, mothers raised communally and now raising their child communally; (2) a Familial group, mothers raised in the family and now raising their child in the family, and (3) a Non-continuous group, mothers raised communally and now raising their child in the family. In keeping with studies with infants, we expected the familial group to show the most security, the communal group to show the least security, and the non-continuous to be in between. Participants were 152 women with school-age children. They reported on their attachment styles and availability of significant others during childhood. Additionally, they evaluated the child-rearing context of themselves and of their children. The three groups did not differ in their attachment security or in the reported availability of significant others in childhood. They differed in their evaluations of their own and their children’s child-rearing contexts. Specifically, they had negative evaluations regarding the communal sleeping arrangement. Security of attachment was related to reported availability of significant others in childhood. These results are discussed in view of the differentiation between contextual-distal variables and process-proximal variables.