bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunophilins, Refsum disease, and lupus nephritis: The peroxisomal enzyme phytanoyl-COA α-hydroxylase is a new FKBP-associated protein
Authors: Chambraud Béatrice , Radanyi Christine , Camonis Jacques H. , Rajkowski Krzysztof , Schumacher Michael , Baulieu Etienne-Emile
Published: July 2002

FKBP52 (FKBP59, FKBP4) is a “macro” immunophilin that, although sharing high structural and functional homologies in its amino-terminal domain with FKBP12 (FKBP1), does not have immunosuppressant activity when complexed with FK506, unlike FKBP12. To investigate the physiological function of FKBP52, we used the yeast two-hybrid system as an approach to find its potential protein partners and, from that, its cellular role. This methodology, which already has allowed us to find the FK506-binding protein (FKBP)-associated protein FAP48, also led to the detection of another FKBP-associated protein. Determination of the sequence of this protein permitted its identification as phytanoyl-CoA α-hydroxylase (PAHX), a peroxisomal enzyme that so far was unknown as an FKBP-associated protein. Inactivation of this enzyme is responsible for Refsum disease in humans. The protein also corresponds to the mouse protein LN1, which could be involved in the progress of lupus nephritis. We show here that PAHX has the physical capacity to interact with the FKBP12-like domain of FKBP52, but not with FKBP12, suggesting that it is a particular and specific target of FKBP52. Whereas the binding of calcineurin to FKBP12 is potentiated by FK506, the specific association of PAHX and FKBP52 is maintained in the presence of FK506. This observation suggests that PAHX is a serious candidate for studying the cellular signaling pathway(s) involving FKBP52 in the presence of immunosuppressant drugs.
Induced mutant mouse lines that express lipoprotein lipase in cardiac muscle, but not in skeletal muscle and adipose tissue, have normal plasma triglyceride and high-density lipoprotein-cholesterol levels
Authors: Levak-Frank Sanja , Hofmann Wolfgang , Weinstock Peter H. , Radner Herbert , Sattler Wolfgang , Breslow Jan L. , Zechner Rudolf
Published: July 2002

The tissue-specific expression of lipoprotein lipase (LPL) in adipose tissue (AT), skeletal muscle (SM), and cardiac muscle (CM) is rate-limiting for the uptake of triglyceride (TG)-derived free fatty acids and decisive in the regulation of energy balance and lipoprotein metabolism. To investigate the tissue-specific metabolic effects of LPL, three independent transgenic mouse lines were established that expressed a human LPL (hLPL) minigene predominantly in CM. Through cross-breeding with heterozygous LPL knockout mice, animals were generated that produced hLPL mRNA and enzyme activity in CM but lacked the enzyme in SM and AT because of the absence of the endogenous mouse LPL gene (L0-hLPL). LPL activity in CM and postheparin plasma of L0-hLPL mice was reduced by 34% and 60%, respectively, compared with control mice. This reduced LPL expression was sufficient to rescue LPL knockout mice from neonatal death. L0-hLPL animals developed normally with regard to body weight and body-mass composition. Plasma TG levels in L0-hLPL animals were increased up to 10-fold during the suckling period but normalized after weaning and decreased in adult animals. L0-hLPL mice had normal plasma high-density lipoprotein (HDL)-cholesterol levels, indicating that LPL expression in CM alone was sufficient to allow for normal HDL production. The absence of LPL in SM and AT did not cause detectable morphological or histopathological changes in these tissues. However, the lipid composition in AT and SM exhibited a marked decrease in polyunsaturated fatty acids. From this genetic model of LPL deficiency in SM and AT, it can be concluded that CM-specific LPL expression is a major determinant in the regulation of plasma TG and HDL-cholesterol levels.
HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy
Authors: Jeffery Katie J. M. , Usuku Koichiro , Hall Sarah E. , Matsumoto Wataru , Taylor Graham P. , Procter Jeanette , Bunce Mike , Ogg Graham S. , Welsh Kenneth I. , Weber Jonathan N. , Lloyd Alun L. , Nowak Martin A. , Nagai Masahiro , Kodama Daisuke , Izumo Shuji , Osame Mitsuhiro , Bangham Charles R. M.
Published: July 2002

The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM/TSP. Here we show that, after infection with HTLV-I, the class I alleleHLA-A*02halves the odds of HAM/TSP (P< 0.0001), preventing 28% of potential cases of HAM/TSP. Furthermore,HLA-A*02+healthy HTLV-I carriers have a proviral load one-third that (P= 0.014) ofHLA-A*02−HTLV-I carriers. An association ofHLA-DRB1*0101with disease susceptibility also was identified, which doubled the odds of HAM/TSP in the absence of the protective effect ofHLA-A*02.These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.
Choroid plexus epithelial expression of
MDR
1
P glycoprotein and multidrug resistance-associated protein contribute to the blood–cerebrospinal-fluid drug-permeability barrier
Authors: Rao Vallabhaneni V. , Dahlheimer Julie L. , Bardgett Mark E. , Snyder Abraham Z. , Finch Rick A. , Sartorelli Alan C. , Piwnica-Worms David
Published: July 2002

The blood–brain barrier and a blood–cerebrospinal-fluid (CSF) barrier function together to isolate the brain from circulating drugs, toxins, and xenobiotics. The blood–CSF drug-permeability barrier is localized to the epithelium of the choroid plexus (CP). However, the molecular mechanisms regulating drug permeability across the CP epithelium are defined poorly. Herein, we describe a drug-permeability barrier in human and rodent CP mediated by epithelial-specific expression of the
MDR1
(multidrug resistance) P glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP). Noninvasive single-photon-emission computed tomography with
99m
Tc-sestamibi, a membrane-permeant radiopharmaceutical whose transport is mediated by both Pgp and MRP, shows a large blood-to-CSF concentration gradient across intact CP epithelium in humans
in vivo
. In rats, pharmacokinetic analysis with
99m
Tc-sestamibi determined the concentration gradient to be greater than 100-fold. In membrane fractions of isolated native CP from rat, mouse, and human, the 170-kDa Pgp and 190-kDa MRP are identified readily. Furthermore, the murine proteins are absent in CP isolated from their respective
mdr1a
/
1b
(−/−) and
mrp
(−/−) gene knockout littermates. As determined by immunohistochemical and drug-transport analysis of native CP and polarized epithelial cell cultures derived from neonatal rat CP, Pgp localizes subapically, conferring an apical-to-basal transepithelial permeation barrier to radiolabeled drugs. Conversely, MRP localizes basolaterally, conferring an opposing basal-to-apical drug-permeation barrier. Together, these transporters may coordinate secretion and reabsorption of natural product substrates and therapeutic drugs, including chemotherapeutic agents, antipsychotics, and HIV protease inhibitors, into and out of the central nervous system.
Oligoribonuclease is an essential component of the mRNA decay pathway
Authors: Ghosh Sandip , Deutscher Murray P.
Published: July 2002

mRNA decay in prokaryotic cells involves the action of both endo- and exoribonucleases. In
Escherichia coli
, degradation of RNA to the mononucleotide level was thought to depend on RNase II and polynucleotide phosphorylase. Here, we show that the enzyme oligoribonuclease is an essential part of this process as well. Thus, inactivation of the
orn
gene encoding oligoribonuclease leads to a cessation of cell growth. Moreover, although pulse-labeled RNA decays normally in
orn
mutant cells under nonpermissive conditions, a large fraction of the resulting products is small oligoribonucleotides rather than the mononucleotides generated in wild-type cells. The oligoribonucleotides that accumulate are 2–5 residues in length; longer molecules disappear during the decay process. These data indicate that oligoribonuclease is required to complete the degradation of mRNA to mononucleotides and that this process is required for cell viability. Inasmuch as close homologues of the
orn
gene are found in a wide range of eukaryotes, extending up to humans, these findings raise the possibility that oligoribonuclease also participates in mRNA degradation in these organisms.
d
-β-Hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease
Authors: Kashiwaya Yoshihiro , Takeshima Takao , Mori Nozomi , Nakashima Kenji , Clarke Kieran , Veech Richard L.
Published: July 2002

The heroin analogue 1-methyl-4-phenylpyridinium, MPP
+
, both
in vitro
and
in vivo
, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Aβ
1–42
, is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM
d
-β-hydroxybutyrate protected cultured mesencephalic neurons from MPP
+
toxicity and hippocampal neurons from Aβ
1–42
toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.
Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia
Authors: Bruick Richard K.
Published: July 2002

The ability to sense and respond to changes in oxygen availability is critical for many developmental, physiological, and pathological processes, including angiogenesis, control of blood pressure, and cerebral and myocardial ischemia. Hypoxia-inducible factor-1α (HIF-1α) is a basic-helix–loop–helix (bHLH)containing member of the PER–ARNT–SIM (PAS) family of transcription factors that plays a central role in the response to hypoxia. HIF-1α, and its relatives HIF-2α/endothelial PAS domain protein (EPAS) and HIF-3α, are induced in response to hypoxia and serve to coordinately activate the expression of target genes whose products facilitate cell survival under conditions of oxygen deprivation. When cells are exposed to chronic hypoxia, the protective response can fail, resulting in apoptosis. This study shows that transcription of the gene encoding Nip3, a proapoptotic member of the Bcl-2 family of cell death factors, is strongly induced in response to hypoxia. The Nip3 promoter contains a functional HIF-1-responsive element (HRE) and is potently activated by both hypoxia and forced expression of HIF-1α. Exposure of cultured cells to chronic hypoxia results in the accumulation of a protein recognized by antibodies raised against Nip3. This study demonstrates a direct link between HIF-1α and a proapoptotic member of the Bcl-2 family and offers a reasonable physiological function for members of the Bcl-2 subfamily, including Nip3 and its close relative Nix. These observations indicate that Nip3 may play a dedicated role in the pathological progression of hypoxia-mediated apoptosis, as observed after ischemic injury.
Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein βγ subunits
Authors: Lei Qiubo , Jones Miller B. , Talley Edmund M. , Schrier Andrew D. , McIntire William E. , Garrison James C. , Bayliss Douglas A.
Published: July 2002

G protein-coupled inwardly rectifying potassium (GIRK) channels can be activated or inhibited by different classes of receptors, suggesting a role for G proteins in determining signaling specificity. Because G protein βγ subunits containing either β1 or β2 with multiple Gγ subunits activate GIRK channels, we hypothesized that specificity might be imparted by β3, β4, or β5 subunits. We used a transfection assay in cell lines expressing GIRK channels to examine effects of dimers containing these Gβ subunits. Inwardly rectifying K
+
currents were increased in cells expressing β3 or β4, with either γ2 or γ11. Purified, recombinant β3γ2 and β4γ2 bound directly to glutathione-
S
-transferase fusion proteins containing N- or C-terminal cytoplasmic domains of GIRK1 and GIRK4, indicating that β3 and β4, like β1, form dimers that bind to and activate GIRK channels. By contrast, β5-containing dimers
inhibited
GIRK channel currents. This inhibitory effect was obtained with either β5γ2 or β5γ11, was observed with either GIRK1,4 or GIRK1,2 channels, and was evident in the context of either basal or agonist-induced currents, both of which were mediated by endogenous Gβγ subunits. In cotransfection assays, β5γ2 suppressed β1γ2-activated GIRK currents in a dose-dependent manner consistent with competitive inhibition. Moreover, we found that β5γ2 could bind to the same GIRK channel cytoplasmic domains as other, activating Gβγ subunits. Thus, β5-containing dimers inhibit Gβγ-stimulated GIRK channels, perhaps by directly binding to the channels. This suggests that β5-containing dimers could act as competitive antagonists of other Gβγ dimers on GIRK channels.
Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: Facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors
Authors: Kalgutkar Amit S. , Crews Brenda C. , Rowlinson Scott W. , Marnett Alan B. , Kozak Kevin R. , Remmel Rory P. , Marnett Lawrence J.
Published: July 2002

All nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) isozymes to different extents, which accounts for their anti-inflammatory and analgesic activities and their gastrointestinal side effects. We have exploited biochemical differences between the two COX enzymes to identify a strategy for converting carboxylate-containing NSAIDs into selective COX-2 inhibitors. Derivatization of the carboxylate moiety in moderately selective COX-1 inhibitors, such as 5,8,11,14-eicosatetraynoic acid (ETYA) and arylacetic and fenamic acid NSAIDs, exemplified by indomethacin and meclofenamic acid, respectively, generated potent and selective COX-2 inhibitors. In the indomethacin series, esters and primary and secondary amides are superior to tertiary amides as selective inhibitors. Only the amide derivatives of ETYA and meclofenamic acid inhibit COX-2; the esters are either inactive or nonselective. Inhibition kinetics reveal that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Site-directed mutagenesis of murine COX-2 indicates that the molecular basis for selectivity differs from the parent NSAIDs and from diarylheterocycles. Selectivity arises from novel interactions at the opening and at the apex of the substrate-binding site. Lead compounds in the present study are potent inhibitors of COX-2 activity in cultured inflammatory cells. Furthermore, indomethacin amides are orally active, nonulcerogenic, anti-inflammatory agents in an
in vivo
model of acute inflammation. Expansion of this approach can be envisioned for the modification of all carboxylic acid-containing NSAIDs into selective COX-2 inhibitors.
Molecular basis for modulation of biological function by alternate splicing of the Wilms' tumor suppressor protein
Authors: Laity John H. , Dyson H. Jane , Wright Peter E.
Published: July 2002

Alternate splicing, leading to the insertion of the tripeptide KTS
in the linker between the third and fourth C
2
H
2
zinc fingers, changes both the DNA-binding function and the subnuclear
localization of the Wilms' tumor suppressor protein (WT1). We
have used NMR relaxation experiments to determine the molecular
basis for the differing DNA recognition properties of the WT1–KTS and
WT1+KTS isoforms. Our results show that the KTS insertion
increases the flexibility of the linker between fingers 3 and 4 and
abrogates binding of the fourth zinc finger to its cognate site in the
DNA major groove. This represents a mechanism whereby a single
zinc-finger gene can be used, through alternate splicing, to fulfill
different functions in the cell.
Effects of environmental enrichment on gene expression in the brain
Authors: Rampon Claire , Jiang Cecilia H. , Dong Helin , Tang Ya-Ping , Lockhart David J. , Schultz Peter G. , Tsien Joe Z. , Hu Yinghe
Published: July 2002

An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents [Hebb, D. O. (1947)Am. Psychol.2, 306–307]. To better understand the molecular mechanisms underlying these experience-dependent cognitive changes, we have used high-density oligonucleotide microarrays to analyze gene expression in the brain. Expression of a large number of genes changes in response to enrichment training, many of which can be linked to neuronal structure, synaptic plasticity, and transmission. A number of these genes may play important roles in modulating learning and memory capacity.
Fluorescence quenching: A tool for single-molecule protein-folding study
Authors: Zhuang Xiaowei , Ha Taekjip , Kim Harold D. , Centner Thomas , Labeit Siegfried , Chu Steven
Published: July 2002

By using titin as a model system, we have demonstrated that fluorescence quenching can be used to study protein folding at the single molecule level. The unfolded titin molecules with multiple dye molecules attached are able to fold to the native state. In the native folded state, the fluorescence from dye molecules is quenched due to the close proximity between the dye molecules. Unfolding of the titin leads to a dramatic increase in the fluorescence intensity. Such a change makes the folded and unfolded states of a single titin molecule clearly distinguishable and allows us to measure the folding dynamics of individual titin molecules in real time. We have also shown that fluorescence quenching can signal folding and unfolding of a small protein with only one immunoglobulin domain.
Biosynthesis of terpenoids: YchB protein of
Escherichia coli
phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2C-methyl-
d
-erythritol
Authors: Lüttgen Holger , Rohdich Felix , Herz Stefan , Wungsintaweekul Juraithip , Hecht Stefan , Schuhr Christoph A. , Fellermeier Monika , Sagner Sylvia , Zenk Meinhart H. , Bacher Adelbert , Eisenreich Wolfgang
Published: July 2002

A comparative analysis of all published complete genomes indicated
that the putative orthologs of the unannotated
ychB
gene
of
Escherichia coli
follow the distribution of the
dxs
,
dxr
, and
ygbP
genes,
which have been shown to specify enzymes of the deoxyxylulose phosphate
pathway of terpenoid biosynthesis, thus suggesting that the
hypothetical YchB protein also is involved in that pathway. To test
this hypothesis, the
E. coli
ychB
gene
was expressed in a homologous host. The recombinant protein was
purified to homogeneity and was shown to phosphorylate
4-diphosphocytidyl-2C-methyl-
d
-erythritol in an
ATP-dependent reaction. The reaction product was identified as
4-diphosphocytidyl-2C-methyl-
d
-erythritol 2-phosphate by
NMR experiments with various
13
C-labeled substrate samples.
A
14
C-labeled specimen of this compound was converted
efficiently into carotenoids by isolated chromoplasts of
Capsicum annuum
. The sequence of
E. coli
YchB protein is similar to that of the protein predicted by the tomato
cDNA pTOM41 (30% identity), which had been implicated in the
conversion of chloroplasts to chromoplasts.
Recent, extensive, and preferential insertion of members of the miniature inverted-repeat transposable element familyHeartbreakerinto genic regions of maize
Authors: Zhang Qiang , Arbuckle John , Wessler Susan R.
Published: July 2002

A 314-bp DNA element calledHeartbreaker-hm1(Hbr-hm1) was previously identified in the 3′ untranslated region of a mutant allele of the maize disease resistance geneHM1. This element has structural features of miniature inverted-repeat transposable elements (MITEs) and is a member of a large family of approximately 4,000 copies in the maize genome. Unlike previously described MITEs, most members of theHbrfamily display over 90% sequence identity. This, coupled with the insertion of anHbrelement into an allele of theHM1gene, suggested that this family might have spread recently throughout the genome. Consistent with this view is the finding thatHbrinsertion sites are remarkably polymorphic. Ten of ten loci containingHbrelements were found to be polymorphic for the presence or absence ofHbramong a collection of maize inbred lines and teosinte strains. Despite the fact that over 80% of the maize genome contain moderate to highly repetitive DNA, we find that randomly chosenHbrelements are predominantly in single or low copy regions. Furthermore, when used to query both the public and private databases of plant genes, over 50% of the sequences flanking theseHbrelements resulted in significant “hits.” Taken together, these data indicate that the presence or absence ofHbrelements is a significant contributory factor to the high level of polymorphism associated with maize genic regions.
Twentieth century climate change: Evidence from small glaciers
Authors: Dyurgerov Mark B. , Meier Mark F.
Published: July 2002

The relation between changes in modern glaciers, not including the ice sheets of Greenland and Antarctica, and their climatic environment is investigated to shed light on paleoglacier evidence of past climate change and for projecting the effects of future climate warming on cold regions of the world. Loss of glacier volume has been more or less continuous since the 19th century, but it is not a simple adjustment to the end of an “anomalous” Little Ice Age. We address the 1961–1997 period, which provides the most observational data on volume changes. These data show trends that are highly variable with time as well as within and between regions; trends in the Arctic are consistent with global averages but are quantitatively smaller. The averaged annual volume loss is 147 mm⋅yr−1in water equivalent, totaling 3.7 × 103km3over 37 yr. The time series shows a shift during the mid-1970s, followed by more rapid loss of ice volume and further acceleration in the last decade; this is consistent with climatologic data. Perhaps most significant is an increase in annual accumulation along with an increase in melting; these produce a marked increase in the annual turnover or amplitude. The rise in air temperature suggested by the temperature sensitivities of glaciers in cold regions is somewhat greater than the global average temperature rise derived largely from low altitude gauges, and the warming is accelerating.
Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance
Authors: Auta James , Guidotti Alessandro , Costa Erminio
Published: July 2002

The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl
−
current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition.
The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the
BHLHB1
gene
Authors: Wang Junjie , Jani-Sait Sheila N. , Escalon Enrique A. , Carroll Andrew J. , de Jong Pieter J. , Kirsch Ilan R. , Aplan Peter D.
Published: July 2002

We have cloned the genomic breakpoints for a balanced t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia. Sequence analysis of the genomic breakpoints indicated that the translocation had been mediated by an illegitimate V(D)J recombination event that disrupted the T-cell receptor (TCR) α locus and placed the TCR α locus enhancer on the derivative 21 chromosome. We identified a previously unreported transcript, designated
BHLHB1
(for basic domain, helix–loop–helix protein, class B, 1) that had been activated by the translocation.
BHLHB1
mapped to the region of chromosome 21 that has been proposed to be responsible, at least in part, for the learning deficits seen in children with Down's syndrome. Although
BHLHB1
expression normally is restricted to neural tissues, T-cell lymphoblasts with the t(14;21)(q11.2;q22) also expressed high levels of
BHLHB1
mRNA. Expression of
BHLHB1
dramatically inhibited E2A-mediated transcription activation in NIH 3T3 fibroblasts and Jurkat T cells. This observation suggests that
BHLHB1
, similar to
SCL/TAL1
, may exert a leukemogenic effect through a functional inactivation of E2A or related proteins.
Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures
Authors: Lee Joon-Kyu , Hurwitz Jerard
Published: July 2002

The minichromosome maintenance (Mcm) proteins 2–7 are required for both the initiation and elongation steps of chromosomal DNA replication. Previous studies have shown that the Mcm complex consisting of the Mcm 4, 6, and 7 proteins contains 3′ to 5′ DNA helicase activity with limited processivity (displacing duplex DNA regions up to 30 nt). In this report, we show that the presence of both 5′ and 3′ single-stranded tails in DNA helicase substrates is essential for the processive helicase activity of the Mcm complex. The presence of both 5′ and 3′ tails facilitated the formation of double heterohexameric complexes of Mcm4/6/7 on substrate DNA, which appeared to be essential for the processive helicase activity. The double heterohexameric complex of Mcm4/6/7, in the presence of a single-strand DNA binding protein, is capable of unwinding duplex DNA region of about 600 bp in length. These results support the hypothesis that the Mcm4/6/7 complex can function as a replication helicase.
‘You'll never walk alone’: CCTV surveillance, order and neo‐liberal rule in Liverpool city centre1
Authors: Coleman Roy , Sim Joe
Published: July 2002

This paper is concerned to chart the establishment and uses of CCTV within the location of Liverpool city centre. In doing this the paper seeks to contextualize CCTV within contemporary ‘partnership’ approaches to regeneration which are reshaping the material and discursive form of the city. Thus CCTV schemes along with other security initiatives are understood as social ordering strategies emanating from within locally powerful networks which are seeking to define and enact orderly regeneration projects. In focusing on the normative aspects of CCTV, the paper raises questions concerning the efficacy of understanding contemporary forms of ‘social ordering practices’ primarily in terms of technical rationalities while neglecting other, more material and ideological processes involved in the construction of social order.
Culture and Negotiation
Authors: Brett Jeanne M.
Published: July 2002

This article develops a model of how culture affects negotiation processes and outcomes. It begins with a description of negotiation from a Western perspective: confrontational, focused on transactions or the resolution of disputes, evaluated in terms of integrative and distributive outcomes. It proposes that power and information processes are fundamental to negotiations and that one impact of culture on negotiations is through these processes. The cultural value of individualism versus collectivism is linked to goals in negotiation; the cultural value of egalitarianism versus hierarchy is linked to power in negotiation; and the cultural value for high versus low context communication is linked to information sharing in negotiation. The article describes why inter‐cultural negotiations pose significant strategic challenges, but concludes that negotiators who are motivated to search for information, and are flexible about how that search is carried out, can reach high‐quality negotiated outcomes.
Mental flexibility as resiliency factor among children exposed to political violence
Authors: Qouta Samir , El‐Sarraj Eyad , Punamäki Raija‐Leena
Published: July 2002

The research focused on mental flexibility versus rigidity in explaining psychological adjustment in the violent conditions of Intifada, and in more peaceful times 3 years later, among 86 Palestinian children. A picture test based on Brunswik (1949) was applied to measure flexible‐rigid cognitive style, and neuroticism, self‐esteem, emotional disorders, and PTSD were used as outcome variables. Results revealed a moderating role of mental flexibility by showing that children were protected from negative long‐term consequences of traumatic events if their perception indicated mental flexibility. However, in the midst of violence mental flexibility was not associated with good psychological adjustment. Mental flexibility was, in turn, determined by environmental and cognitive factors: The more intelligent and the less exposed to traumatic events children were, the higher mental flexibility they showed.
Contribution de l'apprentissage précoce d'une deuxième langue au développement de la conscience linguistique et à l'apprentissage de la lecture
Authors: Demont Elisabeth
Published: July 2002

La présente étude a pour objectif d'évaluer la conscience linguistique et l'efficience en lecture d'enfants apprentis‐lecteurs scolarisés dans un site bilingue (Français‐Allemand). Alors que les chercheurs se sont essentiellement intéressés aux effets du bilinguisme sur le développement des habiletés métalinguistiques, nous nous intéressons pour notre part non seulement aux effets de l'apprentissage précoce d'une deuxième langue sur la conscience linguistique mais également aux relations avec l'apprentissage de la lecture. Nous postulons qu'un enfant exposé à l'apprentissage précoce d'une deuxième langue devrait témoigner d'une conscience syntaxique plus développée et dès lors devrait aborder l'apprentissage de l'écrit avec plus de facilité et présenter ainsi une efficience supérieure en lecture dès les premières étapes de cet apprentissage. Autrement dit, l'apprentissage précoce d'une deuxième langue nous semble ainsi susceptible d'avoir une incidence sur l'apprentissage de la lecture en facilitant la prise de conscience par l'enfant de la structure formelle du langage (et plus particulièrement de sa structure syntaxique). Nos résultats montrent une supériorité des enfants scolarisés depuis l'école maternelle dans un site bilingue: ils obtiennent des performances supérieures à des épreuves de jugement et de correction d'agrammaticalité ainsi qu'à la reconnaissance de mots écrits.
Modern Chinese psychology: Its indigenous roots and international influences
Authors: Jing Qicheng , Fu Xiaolan
Published: July 2002

Psychological thinking in China originated 2000 years ago when Chinese philosophers debated about the goodness and evilness of human nature. In the 16th and 17th centuries the Jesuit missionaries introduced the Catholic scholastic psychology into China. Modern Chinese psychology was mainly introduced from Germany, America, and Japan in the early 20th century. After the founding of the People's Republic of China in 1949, Chinese psychology tried to stage a reform by taking the psychology of the Soviet Union as its model. During the Cultural Revolution (1966–1976) psychology was abandoned due to its Western roots. In the late 1970s psychology was rehabilitated and new fields were opened up for study. Currently, Chinese psychology is adopting a multi‐dimensional approach to meet the demands of China's modernization movement.
Influence of Global Structure on Musical Target Detection and Recognition
Authors: Tillmann Barbara , Bigand Emmanuel
Published: July 2002

The present study adapted a paradigm used in visual perception by Biederman, Glass, and Stacy (1973) and analyzed the influence of a coherent global context on the detection and recognition of musical target excerpts. Global coherence was modified by segmenting minuets into chunks of four, two, or one bar. These chunks were either reordered (Experiments 1, 3, 4, 5) or transposed to different keys (Experiment 2). The results indicate that target detection is influenced only by a reorganization on a very local level (i.e. chunks of one bar). Context incoherence did not influence the recognition of the real targets, but rendered the rejection of wrong target excerpts (foils) more difficult. The present findings revealed only a weak effect of global context on target identification and only for extremely modified structures.
Identifying and Measuring Dimensions of Urban Deprivation in Montreal: An Analysis of the 1996 Census Data
Authors: Langlois Andre , Kitchen Peter
Published: July 2002

This paper uses data from the 1996 Canadian census to examine and measure the spatial structure and intensity of urban deprivation in Montreal. Urban deprivation emerged as an important theme in urban studies and urban geography during the 1990s. Since the early 1980s, the Montreal urban area, particularly the Island of Montreal, has experienced an increase in urban social problems, brought on largely by economic restructuring, recessions and the out-migration of residents and businesses to suburban communities. Twenty indicators of urban deprivation are drawn from the census and analysed by way of a principal components analysis first to identify the main types of deprivation in the city and then to measure its intensity. In the process, a general deprivation index (GDI) is devised which can be applied to study the spatial aspects of this phenomenon in other Canadian cities. The study identified six main types of deprivation in the city and found that they were most visible on the Island of Montreal, especially in the central and eastern parts. Additionally, it found that urban deprivation in not confined to the inner city, as several of the most severely deprived neighbourhoods are located outside the central city and even in the off-Island suburbs.
The Effect of Foreign Investment on the Real Estate Industry in China
Authors: Jiang Dianchun , Chen Jean Jinghan , Isaac David
Published: July 2002

This paper discusses the development of real estate industry in China in recent years. It argues that Hayek's theory of economic fluctuations can help to explain the contraction of the real estate market in 1994 in China as a whole. However, as a theory of the closed economy, Hayek's theory is found to be no longer robust when applied to cities where there is heavy foreign direct investment, such as Shanghai. We believe that it is the foreign direct investment that is making the real estate industry in Shanghai perform well, despite the government's tight monetary policy and the contraction of the industry in other parts of the country over the same period. The paper also argues that, while most foreign investment in real estate is classified as direct investment, it is very different from 'typical' foreign direct investment except in form and in fact shares most of the characteristics of portfolio investment. Foreign direct investment in real estate reflects the imperfections of China's capital markets.
Negotiating Public Space: Strategies and Styles of Migrant Female Domestic Workers in Singapore
Authors: Yeoh Brenda S. A. , Huang Shirlena
Published: July 2002

This paper investigates migrant domestic workers as a marginalised group in Singapore's urban landscape by examining the ways in which their social maps are structured and negotiated in relation to public space. It argues that the phenomenon of the 'divided city' evident in capitalist societies which reflects and reinforces the sexual division of labour in general is even more salient in the lived experiences of migrant female domestic workers who must contend not simply with the spatial expressions of patriarchy, but also with racialisation and other means of segregation. However, it is clear that these women are not entirely passive recipients of dominant practices and ideas, but are capable of different styles and strategies in the use, colonisation and even contestation of public domains.
Public Choice, Pigouvian and Coasian Planning Theory
Authors: Webster Christopher J.
Published: July 2002

With urban planning policy in transition in many parts of the world, the need to understand the theoretical bases for planning and to ground discussion about policy innovations on theory is as important as ever. This essay reviews the relevance of three economic paradigms to the theory of development control. It is written as a technical review with the purpose of explaining, contrasting and contextualising the contributions of these paradigms. Much has been written about the Pigouvian case for regulative planning. The Coasian literature is strong especially in the US but is not so well known elsewhere; and little has been written that draws together the diverse perspectives offered by the public choice school. This essay has been written particularly for academic planners and urban social scientists in the UK, and in other European and Commonwealth countries who are not familiar with the technical arguments underlying the Coase vs Pigou zoning debate. It is also an essay on the public choice theory of planning since it contextualises Coasian planning theory within that wider critique of welfare economics. Among other points, it argues that the relevance of Coasian planning theory is not by any means restricted to US-style zoning, nor is it purely a debate about deregulation. Coasian and other public choice perspectives generate a rich source of theoretical and empirical propositions which should be tested and developed, particularly as frameworks for comparative analysis of planning constitutions and policies. In this spirit, the essay concludes with elements of a research agenda.
Student Attitudes, Image and the Gender Gap
Authors: Warrington M. , Younger M. , Williams J.
Published: July 2002

ABSTRACT This article, based on a 3 year study in East Anglian schools, draws on a range of evidence pointing to different attitudes of girls and boys to General Certificate of Secondary Education (GCSE) work. Suggestions are made to account for these differences, with particular emphasis being placed on peer pressure, image and social groupings. Although these are relevant to both sexes, it was found to be more acceptable for girls to work hard and still be part of the ‘in crowd’, whilst boys were under greater pressure to conform to a ‘cool’, masculine image, and were more likely to be ridiculed for working hard. The article concludes by suggesting that one approach to closing the current gender gap may be to enable boys in school to move beyond the stereotypical image of the macho male.
Youth recreation centre participation and criminal offending: A 20-year longitudinal study of Swedish boys
Authors: Mahoney Joseph L. , Stattin Hakan , Magnusson David
Published: July 2002

This study assessed whether participation in Swedish youth recreation centres (Fritidsgardar) is related to long-term criminality assessed from late childhood to mid adulthood. A prospective, longitudinal investigation of a representative cohort of 498 boys from a medium-sized Swedish community was employed. A pattern-analysis identi” ed ” ve configurations of boys who showed different profiles of social and academic competence at the age of 10. The configurations were compared with respect to juvenile and adult criminality for boys who did, and who did not, make the decision to participate in a youth recreation centre at age 13. Results showed that participation in youth centres was nonrandom. Boys with a multiple problem profile of both social and academic problems in school at age 10 showed more frequent participation in recreation centres at age 13. The frequency of criminal offending increased for all configurations of boys who became involved in a recreation centre. Frequent participation in youth centres was linked to high rates of juvenile offending and persistent offending (i.e., registered for one or several offences both as a juvenile and as an adult). These ” ndings held after controlling for individual, family, and economic factors prior to involvement in the youth centre. The limitations of the ” ndings and their implications for social policy are discussed.
Face-to-face emotion interaction studies in Down syndrome infants
Authors: Carvajal Fernando , Iglesias Jaime
Published: July 2002

Infants with Down syndrome constitute an ideal population for analysing the development of emotional expression from the first months of life, due basically to the fact that this chromosomal alteration is identifiable from birth and results in well-known difficulties of cognitive development and in basic learning processes. Taking into account the functional aspects of facial expression during initial social interaction, in this review we present a series of studies which, although based on different theoretical approaches and different methodologies, have the common objective of analysing the emotional behaviour of young infants with and without Down syndrome during face-to-face interaction with their mothers. The main conclusions emerging from these studies are: (a) that, as in the case of typically developing infants, Down syndrome infants and their mothers present a series of coordinated and interdependent expressive interchanges; (b) that, despite the differences found between infants with and without Down syndrome in quantitative parameters of expressive behaviour, such as frequency, duration and intensity of the different emotional expressions or their point of initiation in development, what seems to be most significant is the clear functional similarity observed in the two groups of subjects during initial mother-infant interaction; and (c) that these differences may be understood by considering different psychobiological explanations as well as the known cognitive deficits.
“When I have a Bad Dream, Mommy Holds Me”: Preschoolers’ Conceptions of Emotions, Parental Socialisation, and Emotional Competence
Authors: Denham Susanne A.
Published: July 2002

Described preschoolers’ conceptions of the consequences of their own emotions within the family demonstrated the linkage between this aspect of social cognition and emotional competence with peers, and examined contributions of parental emotion to both child variables. A total of 77 4- and 5-year-olds enacted dollhouse vignettes depicting consequences of their emotions. Parents completed questionnaires on negative emotion and sharing of positive affect, and teachers rated children’s emotional competence with peers. Children attributed plausible parental reactions to their own emotions; affective sharing/distress relief conceptions of parents’ reactions were most strongly associated with emotional competence in the preschool classroom. Socialisation of emotion indices exerted both direct and indirect influences on emotional competence, and conceptions of parents’ positive reactions also exerted a direct effect, as expected.
Maternal Interactive Behaviour in Early Infancy and Later Attachment
Authors: Völker Susanne , Keller Heidi , Lohaus Arnold , Cappenberg Martina , Chasiotis Athanasios
Published: July 2002

Evolutionary considerations (cf. MacDonald, 1992) suggest that emotional closeness and security of attachment address different functional systems. We assume that maternal sensitivity during early face-to-face interactions is related to later emotional closeness, whereas the contingency of maternal reactions towards the infant’s signals is related to later security of attachment. Forty-three mother-infant dyads were videotaped at home during face-to-face interactions when the infants were 3 months old, and were seen in the strange situation when the infants were 12 months old. Results confirm the assumptions, with significant correlations between early face-to-face sensitivity and later contact seeking, maintaining, and avoiding behaviour of the infant during the reunion episodes of the strange situation. Early maternal face-to-face contingency was related to later security of attachment.
Enhancing Effects of Oltipraz on the Development of Spontaneous Hepatic Lesions in LEC Rats
Authors: Nakamura Hideaki , Okazaki Kazushi , Nishikawa Akiyoshi , Furukawa Fumio , Kasahara Ken-Ichiro , Miyauchi Makoto , Imazawa Takayoshi , Uchida Koji , Hirose Masao
Published: July 2002

Oltipraz, developed as an antischistosomal agent, protects against the hepatotoxicity of many xenobiotics and is known to be an effective inhibitor of experimental carcinogenesi s in rodents. In the present study, we investigated its effects on the development of lesions in LEC rats, established as a mutant strain characterized by a hereditary predisposition for hepatic damage with severe jaundice. A total of 35 male 6-week-old LEC rats were divided into 2 groups, one administered diet supplemented with oltipraz at a dose of 400 ppm, and the other fed basal diet alone. Animals in each group were sequentially sacrificed at 10, 15, and 25 weeks after commencement of the oltipraz administration. Eight animals died or became moribund in the oltipraz group during weeks 10 and 11 of the treatment, whereas only one rat in the nontreatment group died after 16 weeks. All dead or moribund animals showed severe or moderate jaundice. The treatment caused a decrease in body weight gain from 9 to 13 weeks, and an increase in relative liver weight at each sacrifice point. Serum biochemical assays performed at week 25 revealed elevated levels of serum AST, ALT, LDH, ALP, γ -GTP, and Cu in the treated-animals. The glutathione level in the livers of oltipraz-treated animals was significantly higher than that in the control rats. Histopathologically, enlarged hepatocytes with large nuclei, focal necrosis, pigment granule-laden Kupffer cells and hypertrophy of renal tubule cells were observed in both groups, but the severity of these changes was greater in the oltipraz group. Our results thus indicate that spontaneous hepatic damage in LEC rats is enhanced by oltipraz, by a mechanism that remains to be elucidated.