bluuebunny/crossref_metadata_2025 huggingface dataset:
Pax6
is essential for establishing ventral-dorsal cell boundaries in pituitary gland development
Authors: Kioussi Chrissa , O’Connell Shawn , St-Onge Luc , Treier Mathias , Gleiberman Anatoli S. , Gruss Peter , Rosenfeld Michael G.
Published: July 2002

Pax6
, a highly conserved member of the paired homeodomain transcription factor family that plays essential roles in ocular, neural, and pancreatic development and effects asymmetric transient dorsal expression during pituitary development, with its expression extinguished before the ventral → dorsal appearance of specific cell types. Analysis of pituitary development in the
Small eye
and
Pax6
−/− mouse mutants reveals that the dorsoventral axis of the pituitary gland becomes ventralized, with dorsal extension of the transcriptional determinants of ventral cell types, particularly
PFrk
. This ventralization is followed by a marked decrease in terminally differentiated dorsal somatotrope and lactotrope cell types and a marked increase in the expression of markers of the ventral thyrotrope cells and SF-1-expressing cells of gonadotrope lineage. We suggest that the transient dorsal expression of
Pax6
is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of
Shh
ventral signals.
Enhancing versus suppressive effects of stress hormones on skin immune function
Authors: Dhabhar Firdaus S. , McEwen Bruce S.
Published: July 2002

Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.
Skeletal and dental morphology supports diphyletic origin of baboons and mandrills
Authors: Fleagle John G. , McGraw W. Scott
Published: July 2002

Numerous biomolecular studies from the past 20 years have indicated that the large African monkeys
Papio
,
Theropithecus
, and
Mandrillus
have a diphyletic relationship with different species groups of mangabeys. According to the results of these studies, mandrills and drills (
Mandrillus
) are most closely related to the
torquatus
–
galeritus
group of mangabeys placed in the genus
Cercocebus
, whereas baboons (
Papio
) and geladas (
Theropithecus
) are most closely related to the
albigena
–
aterrimus
mangabeys, now commonly placed in the genus
Lophocebus
. However, there has been very little morphological evidence linking mandrills on the one hand and baboons and geladas on the other with different groups of mangabeys. In a study of mangabey locomotion and skeletal anatomy, we have identified features of the postcranial skeleton and the dentition that support the molecular phylogeny and clearly link mandrills with
Cercocebus
and
Papio
with
Lophocebus
. Moreover, the features linking
Cercocebus
and
Mandrillus
accord with ecological studies of these species indicating that these two genera are a cryptic clade characterized by unique adaptations for gleaning insects, hard nuts, and seeds from the forest floor.
Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage
Authors: Hendrix Roger W. , Smith Margaret C. M. , Burns R. Neil , Ford Michael E. , Hatfull Graham F.
Published: July 2002

We report DNA and predicted protein sequence similarities, implying homology, among genes of double-stranded DNA (dsDNA) bacteriophages and prophages spanning a broad phylogenetic range of host bacteria. The sequence matches reported here establish genetic connections, not always direct, among the lambdoid phages of
Escherichia coli
, phage φC31 of
Streptomyces
, phages of
Mycobacterium
, a previously unrecognized cryptic prophage, φflu, in the
Haemophilus influenzae
genome, and two small prophage-like elements, φRv1 and φRv2, in the genome of
Mycobacterium tuberculosis
. The results imply that these phage genes, and very possibly all of the dsDNA tailed phages, share common ancestry. We propose a model for the genetic structure and dynamics of the global phage population in which all dsDNA phage genomes are mosaics with access, by horizontal exchange, to a large common genetic pool but in which access to the gene pool is not uniform for all phage.
A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca
2+
release channel function and severe central core disease
Authors: Lynch Patrick J. , Tong Jiefei , Lehane Mary , Mallet Alejandro , Giblin Linda , Heffron James J. A. , Vaughan Pat , Zafra Gildardo , MacLennan David H. , McCarthy Tommie V.
Published: July 2002

Central core disease is a rare, nonprogressive myopathy that is characterized by hypotonia and proximal muscle weakness. In a large Mexican kindred with an unusually severe and highly penetrant form of the disorder, DNA sequencing identified an I4898T mutation in the C-terminal transmembrane/luminal region of the RyR1 protein that constitutes the skeletal muscle ryanodine receptor. All previously reported
RYR1
mutations are located either in the cytoplasmic N terminus or in a central cytoplasmic region of the 5,038-aa protein. The I4898T mutation was introduced into a rabbit
RYR1
cDNA and expressed in HEK-293 cells. The response of the mutant RyR1 Ca
2+
channel to the agonists halothane and caffeine in a Ca
2+
photometry assay was completely abolished. Coexpression of normal and mutant
RYR1
cDNAs in a 1:1 ratio, however, produced RyR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca
2+
release were reduced by 67%. [
3
H]Ryanodine binding indicated that the heterozygous channel is activated by Ca
2+
concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca
2+
level and a significantly reduced luminal Ca
2+
level. These data are indicative of a leaky channel, possibly caused by a reduction in the Ca
2+
concentration required for channel activation. Comparison with two other coexpressed mutant/normal channels suggests that the I4898T mutation produces one of the most abnormal RyR1 channels yet investigated, and this level of abnormality is reflected in the severe and penetrant phenotype of affected central core disease individuals.
Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus
Authors: Liu Hantao , Mazarati Andrey M. , Katsumori Hiroshi , Sankar Raman , Wasterlain Claude G.
Published: July 2002

Substance P (SP), a member of the tachykinin family, is widely distributed in the central nervous system and is involved in a variety of physiological processes including cardiovascular function, inflammatory responses, and nociception. We show here that intrahippocampal administration of SP triggers self-sustaining status epilepticus (SSSE) in response to stimulation of the perforant path for periods too brief to have any effect in control rats, and this SSSE generates a pattern of acute hippocampal damage resembling that known to occur in human epilepsy. The SP receptor (SPR) antagonists, spantide II and RP-67,580, block both the initiation of SSSE and SSSE-induced hippocampal damage and terminate established anticonvulsant-resistant SSSE. SSSE results in a rapid and dramatic increase in the expression of preprotachykinin A (a precursor of SP) mRNA and SP in principal neurons in CA3, CA1, and the dentate gyrus as well as in hippocampal mossy fibers. SP also increases glutamate release from hippocampal slices. Enhanced expression of SP during SSSE may modulate hippocampal excitability and contribute to the maintenance of SSSE. Thus, SPR antagonists may constitute a novel category of drugs in antiepileptic therapy.
Werner protein recruits DNA polymerase δ to the nucleolus
Authors: Szekely Anna M. , Chen Yao-Hui , Zhang Chunyu , Oshima Junko , Weissman Sherman M.
Published: July 2002

Werner syndrome is a Mendelian disorder of man that produces a
number of manifestations resembling human aging. This disorder is
caused by inactivation of the
wrn
gene, a member of the
RecQ family of DNA helicases. The helicase and exonuclease activities
of the Werner protein (WRN) suggest that it functions in DNA
transactions, but the physiological function of WRN remains elusive. We
present several lines of evidence that WRN interacts specifically with
the p50 subunit of polymerase δ, the major DNA polymerase required
for chromosomal DNA replication. P50, identified by yeast two-hybrid
screening, interacts physically with the C terminus of WRN. Native WRN
protein coimmunoprecipitates with p50 in a cellular fraction enriched
in nucleolar proteins, and this immunocomplex also includes p125, the
catalytic subunit of polymerase δ. In subcellular localization
studies of cells transfected with WRN, p50 and p125 redistribute to the
nucleolus and colocalize with WRN. These results suggest that one of
the functions of WRN protein is to directly modify DNA replication via
its interaction with p50 and abet dynamic relocalization of the DNA
polymerase δ complexes within the nucleus.
Furin-mediated processing in the early secretory pathway: Sequential cleavage and degradation of misfolded insulin receptors
Authors: Bass Joseph , Turck Christopher , Rouard Mathias , Steiner Donald F.
Published: July 2002

Improperly folded membrane proteins are retained in the endoplasmic reticulum and then diverted to a degradative pathway by a network of molecular chaperones and intracellular proteases. Here we report that mutant insulin proreceptors (Pro62) retained in the early secretory pathway undergo proteolytic cleavage at a tetrabasic concensus site for the subtilisin-like protease furin (SPC 1), generating two unstable proteolytic intermediates of 80/120 kDa corresponding to α (135 kDa) and β (90 kDa) subunits. These are degraded more rapidly than the uncleaved proreceptor protein. Site-directed mutagenesis of the normal RKRR processing site prevented cleavage. Use of inhibitors and furin-deficient cell lines confirmed that furin is responsible for proreceptor cleavage; furin overexpression increased the degradation of mutant but not wild-type receptors. Together, these results suggest that processing and degradation occur sequentially for mutant proreceptors.
Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1
Authors: Nguyen Minh Dang , Larivière Roxanne C. , Julien Jean-Pierre
Published: July 2002

It is well established that motor neurons with large axon caliber
are selectively affected in amyotrophic lateral sclerosis (ALS). To
investigate whether high neurofilament (NF) content and large axonal
caliber are factors that predispose motor neurons to selective
degeneration in ALS, we generated mice expressing a mutant form of
superoxide dismutase 1 (SOD1
G37R
) linked to familial ALS in
a context of one allele for each NF gene being disrupted. A ≈40%
decrease of NF protein content detected in triple heterozygous knockout
mice shifted the calibers of large axons in L5 ventral root from 5–9
μm to 1–5 μm, altering neither the normal subunit stoichiometry
and morphological distribution of NFs nor levels of other cytoskeletal
proteins. This considerable reduction in NF burden and caliber of axons
did not extend the life span of SOD1
G37R
mice nor did it
alleviate the loss of motor axons. Moreover, increasing the density of
NFs in axons by overexpressing a NF-L transgene did not accelerate
disease in SOD1
G37R
mice. These results do not support the
current view that high NF content and large caliber of axons may
account for the selective vulnerability of motor neurons in ALS caused
by mutant SOD1.
Ubiquitin is part of the retrovirus budding machinery
Authors: Patnaik Akash , Chau Vincent , Wills John W.
Published: July 2002

Retroviruses contain relatively large amounts of ubiquitin, but the
significance of this finding has been unknown. Here, we show that drugs
that are known to reduce the level of free ubiquitin in the cell
dramatically reduced the release of Rous sarcoma virus, an avian
retrovirus. This effect was suppressed by overexpressing ubiquitin and
also by directly fusing ubiquitin to the C terminus of Gag, the viral
protein that directs budding and particle release. The block to budding
was found to be at the plasma membrane, and electron microscopy
revealed that the reduced level of ubiquitin results in a failure of
mature virus particles to separate from each other and from the plasma
membrane during budding. These data indicate that ubiquitin is actually
part of the budding machinery.
National burden of disease in India from indoor air pollution
Authors: Smith Kirk R.
Published: July 2002

In the last decade, a number of quantitative epidemiological
studies of specific diseases have been done in developing countries
that for the first time allow estimation of the total burden of disease
(mortality and morbidity) attributable to use of solid fuels in adult
women and young children, who jointly receive the highest exposures
because of their household roles. Few such studies are available as yet
for adult men or children over 5 years. This paper evaluates the
existing epidemiological studies and applies the resulting risks to the
more than three-quarters of all Indian households dependent on such
fuels. Allowance is made for the existence of improved stoves with
chimneys and other factors that may lower exposures. Attributable risks
are calculated in reference to the demographic conditions and patterns
of each disease in India. Sufficient evidence is available to estimate
risks most confidently for acute respiratory infections (ARI), chronic
obstructive pulmonary disease (COPD), and lung cancer. Estimates for
tuberculosis (TB), asthma, and blindness are of intermediate
confidence. Estimates for heart disease have the lowest confidence.
Insufficient quantitative evidence is currently available to estimate
the impact of adverse pregnancy outcomes (e.g., low birthweight and
stillbirth). The resulting conservative estimates indicate that some
400–550 thousand premature deaths can be attributed annually to use of
biomass fuels in these population groups. Using a disability-adjusted
lost life-year approach, the total is 4–6% of the Indian national
burden of disease, placing indoor air pollution as a major risk factor
in the country.
Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1)
Authors: Poukka Hetti , Karvonen Ulla , Jänne Olli A. , Palvimo Jorma J.
Published: July 2002

Modification by SUMO-1 is proposed to play a role in protein
targeting and/or stability. The SUMO-1-conjugating enzyme Ubc9
interacts with androgen receptor (AR), a ligand-activated transcription
factor belonging to the steroid receptor superfamily. We show here that
AR is covalently modified by SUMO-1 (sumoylated) in an
androgen-enhanced fashion and identify the principal acceptor site in
the N-terminal domain of AR. Substitutions of sumoylated Lys residues
enhanced transcriptional activity of AR without influencing its
transrepressing activity. Interestingly, the same Lys residues form the
cores of the recently described transcriptional synergy control motifs
in AR [Iñiguez-Lluhi, J. A. & Pearce, D. (2000)
Mol.
Cell. Biol
. 20, 6040–6050]. These motifs, which match
perfectly with the sumoylation consensus sequence, are also present in
the N-terminal domains of glucocorticoid, mineralocorticoid, and
progesterone receptor. Taken together, our data suggest that reversible
sumoylation is a mechanism for regulation of steroid receptor function.
The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death
Authors: Beltrán Belén , Mathur Anthony , Duchen Michael R. , Erusalimsky Jorge D. , Moncada Salvador
Published: July 2002

The mitochondrion is a key organelle in the control of cell death. Nitric oxide (NO) inhibits complex IV in the respiratory chain and is reported to possess both proapoptotic and antiapoptotic actions. We investigated the effects of continuous inhibition of respiration by NO on mitochondrial energy status and cell viability. Serum-deprived human T cell leukemia (Jurkat) cells were exposed to NO at a concentration that caused continuous and complete (∼85%) inhibition of respiration. Serum deprivation caused progressive loss of mitochondrial membrane potential (Δψm) and apoptotic cell death. In the presence of NO, Δψmwas maintained compared to controls, and cells were protected from apoptosis. Similar results were obtained by using staurosporin as the apoptotic stimulus. As exposure of serum-deprived cells to NO progressed (>5 h), however, Δψmfell, correlating with the appearance of early apoptotic features and a decrease in cell viability. Glucose deprivation or iodoacetate treatment of cells in the presence of NO resulted in a collapse of Δψm, demonstrating involvement of glycolytic ATP in its maintenance. Under these conditions cell viability also was decreased. Treatment with oligomycin and/or bongkrekic acid indicated that the maintenance of Δψmduring exposure to NO is caused by reversal of the ATP synthase and other electrogenic pumps. Thus, blockade of complex IV by NO initiates a protective action in the mitochondrion to maintain Δψm; this results in prevention of apoptosis. It is likely that during cellular stress involving increased generation of NO this compound will trigger a similar sequence of events, depending on its concentration and duration of release.
Up-regulation of the chondrogenicSox9gene by fibroblast growth factors is mediated by the mitogen-activated protein kinase pathway
Authors: Murakami Shunichi , Kan Mikio , McKeehan Wallace L. , de Crombrugghe Benoit
Published: July 2002

Recent experiments have established that Sox9 is required for chondrocyte differentiation. Here, we show that fibroblast growth factors (FGFs) markedly enhanceSox9expression in mouse primary chondrocytes as well as in C3H10T1/2 cells that express low levels ofSox9. FGFs also strongly increase the activity of a Sox9-dependent chondrocyte-specific enhancer in the gene for collagen type II. Transient transfection experiments using constructs encoding FGF receptors strongly suggested that all FGF receptors, FGFR1–R4, can transduce signals that lead to the increase inSox9expression. The increase in Sox9 levels induced by FGF2 was inhibited by a specific mitogen-activated protein kinase kinase (MAPKK)/mitogen-activated protein kinase/ERK kinase (MEK) inhibitor U0126 in primary chondrocytes. In addition, coexpression of a dual-specificity phosphatase, CL100/MKP-1, that is able to dephosphorylate and inactivate mitogen-activated protein kinases (MAPKs) inhibited the FGF2-induced increase in activity of the Sox9-dependent enhancer. Furthermore, coexpression of a constitutively active mutant of MEK1 increased the activity of the Sox9-dependent enhancer in primary chondrocytes and C3H10T1/2 cells, mimicking the effects of FGFs. These results indicate that expression of the gene for the master chondrogenic factor Sox9 is stimulated by FGFs in chondrocytes as well as in undifferentiated mesenchymal cells and strongly suggest that this regulation is mediated by the MAPK pathway. Because Sox9 is essential for chondrocyte differentiation, we propose that FGFs and the MAPK pathway play an important role in chondrogenesis.
Paleoproterozoic snowball Earth: Extreme climatic and geochemical global change and its biological consequences
Authors: Kirschvink Joseph L. , Gaidos Eric J. , Bertani L. Elizabeth , Beukes Nicholas J. , Gutzmer Jens , Maepa Linda N. , Steinberger Rachel E.
Published: July 2002

Geological, geophysical, and geochemical data support a theory that Earth experienced several intervals of intense, global glaciation (“snowball Earth” conditions) during Precambrian time. This snowball model predicts that postglacial, greenhouse-induced warming would lead to the deposition of banded iron formations and cap carbonates. Although global glaciation would have drastically curtailed biological productivity, melting of the oceanic ice would also have induced a cyanobacterial bloom, leading to an oxygen spike in the euphotic zone and to the oxidative precipitation of iron and manganese. A Paleoproterozoic snowball Earth at 2.4 Giga-annum before present (Ga) immediately precedes the Kalahari Manganese Field in southern Africa, suggesting that this rapid and massive change in global climate was responsible for its deposition. As large quantities of O
2
are needed to precipitate this Mn, photosystem II and oxygen radical protection mechanisms must have evolved before 2.4 Ga. This geochemical event may have triggered a compensatory evolutionary branching in the Fe/Mn superoxide dismutase enzyme, providing a Paleoproterozoic calibration point for studies of molecular evolution.
RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism
Authors: Li Ji , Sarosi Ildiko , Yan Xiao-Qiang , Morony Sean , Capparelli Casey , Tan Hong-Lin , McCabe Susan , Elliott Robin , Scully Sheila , Van Gwyneth , Kaufman Stephen , Juan Shao-Chieh , Sun Yu , Tarpley John , Martin Laura , Christensen Kathleen , McCabe James , Kostenuik Paul , Hsu Hailing , Fletcher Frederick , Dunstan Colin R. , Lacey David L. , Boyle William J.
Published: July 2002

We have generated RANK (receptor activator of NF-κB) nullizygous mice to determine the molecular genetic interactions between osteoprotegerin, osteoprotegerin ligand, and RANK during bone resorption and remodeling processes.
RANK
−/−
mice lack osteoclasts and have a profound defect in bone resorption and remodeling and in the development of the cartilaginous growth plates of endochondral bone. The osteopetrosis observed in these mice can be reversed by transplantation of bone marrow from
rag1
−/−
(recombinase activating gene 1) mice, indicating that
RANK
−/−
mice have an intrinsic defect in osteoclast function. Calciotropic hormones and proresorptive cytokines that are known to induce bone resorption in mice and human were administered to
RANK
−/−
mice without inducing hypercalcemia, although tumor necrosis factor α treatment leads to the rare appearance of osteoclast-like cells near the site of injection. Osteoclastogenesis can be initiated in
RANK
−/−
mice by transfer of the
RANK
cDNA back into hematopoietic precursors, suggesting a means to critically evaluate RANK structural features required for bone resorption. Together these data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.
Divergence of larval morphology betweenDrosophila sechelliaand its sibling species caused by cis-regulatory evolution ofovo/shaven-baby
Authors: Sucena Élio , Stern David L.
Published: July 2002

We report an extreme morphological difference betweenDrosophila sechelliaand related species of the pattern of hairs on first-instar larvae. On the dorsum of most species, the posterior region of the anterior compartment of most segments is covered by a carpet of fine hairs. InD. sechellia,these hairs have been lost and replaced with naked cuticle. Genetic mapping experiments and interspecific complementation tests indicate that this difference is caused, in its entirety, by evolution at theovo/shaven-babylocus. The pattern of expression of theovo/shaven-babytranscript is correlated with this morphological change. The altered dorsal cuticle pattern is probably caused by evolution of the cis-regulatory region ofovo/shaven-babyin theD. sechellialineage.
The surveillant assemblage
Authors: Haggerty Kevin D. , Ericson Richard V.
Published: July 2002

George Orwell's ‘Big Brother’ and Michel Foucault's ‘panopticon’ have dominated discussion of contemporary developments in surveillance. While such metaphors draw our attention to important attributes of surveillance, they also miss some recent dynamics in its operation. The work of Gilles Deleuze and Felix Guattari is used to analyse the convergence of once discrete surveillance systems. The resultant ‘surveillant assemblage’ operates by abstracting human bodies from their territorial settings, and separating them into a series of discrete flows. These flows are then reassembled in different locations as discrete and virtual ‘data doubles’. The surveillant assemblage transforms the purposes of surveillance and the hierarchies of surveillance, as well as the institution of privacy.
The psychological adaptation of overseas and migrant students in Australia
Authors: Leung Cynthia
Published: July 2002

This study aimed to examine the psychological adaptation of overseas and migrant students, and Anglo‐Australian students, in the light of various individual variables including social self‐efficacy, locus of control, loneliness, age, sex, and acculturating group membership. Participants were 382 students attending various universities in Melbourne, Australia. There were 189 Anglo‐Australian students, 72 Southern‐European second‐generation migrant students, 33 Asian migrant students, 33 Chinese migrant students, and 55 Chinese overseas students. The results suggested that there were ethnic differences in loneliness, social self‐efficacy, locus of control, and academic satisfaction. For nonmigrant students, a sense of control was important to their psychological and academic adaptation whereas for migrant/overseas students, supportive social relationships were important for their psychological and academic adaptation. The implications of these results for service provisions to students were also discussed.
Predicting persistence or withdrawal in female handballers with social exchange theory
Authors: Guillet E. , Sarrazin P. , Carpenter P.J. , Trouilloud D. , Cury F.
Published: July 2002

Two complementary studies were conducted to explain the dropout phenomenon with French female handball players, utilizing the tenets of social exchange theory (Thibaut & Kelley, 1959; Rusbult, 1980). In the first study, the aim was to more fully explore the sources of enjoyment by emphasizing the key variables in the costs/benefits analysis. We postulate that the costs/benefits analysis consists in each athlete estimating the probability of reaching the most desired consequences for him or her (e.g., learn and improve skill, affiliation with others, be better than the others). The subjects were 488 French women aged from 15–19 years. Structural equation modeling (SEM) revealed that enjoyment in handball was predicted by a latent variable (named perceived benefits) subjacent to perceptions of competence, autonomy, relatedness, progress, coach's support, and time of play. In the second study, we tested a sport commitment model based on the social exchange postulates, using SEM analyses and a prospective design over 8 months. In view of the results of study 1, we replaced the construct of enjoyment with perceived benefit. This analysis provides a more comprehensive understanding of the enjoyment construct and is more consistent with the notion of cost and benefits outlined in social exchange theory. Participants were 253 French handball players between the ages of 14 and 16 years. A first set of analyses, focused on the differences, showed that dropout players perceived themselves as significantly less competent, less autonomous, less related to their team, lower in progress and less supported by their coach than persistent players. The second set of analyses with SEM revealed that the commitment level was positively associated with perceived benefits and negatively with social constraints and alternatives opportunities. Finally, a lack of commitment led to dropping out of the sport 8‐months later.
Heritage as Knowledge: Capital or Culture?
Authors: Graham Brian
Published: July 2002

This paper discusses the relationships between heritage and the knowledge-based city. Heritage itself is conceptualised as the meanings attached in the present to the past and is regarded as a knowledge defined within social, political and cultural contexts. It is admitted, however, that there is relatively little research in this area and that the role of heritage in the knowledge economy still has to be adequately articulated. The discussion points to the complex conflicts inherent within heritage due to it being a knowledge that fulfils many different economic and cultural uses. These are explained through the idea of 'external' and 'internal' cities. Finally, the paper makes some preliminary connections between heritage, the knowledge-base and the city, pointing to the importance of heritage in creating the representations of place within which the knowledge economy remains firmly rooted.
The Impact of Tourism on Residential Experience in Central-eastern Europe: The Development of a New Legitimation Crisis in the Czech Republic
Authors: Cooper Charlie , Morpeth Nigel
Published: July 2002

This paper argues that rapid and unfettered commercial tourism development in the historic core of Prague is playing a major role in the transformation of its social, spatial and cultural characteristics, changes which are encapsulating residential experience. Whilst recognising the potential positive economic benefits of tourism, we argue that the inherent pressures of commercialisation and touristification are creating new tensions which, if not addressed, are likely to contribute significantly to the creation of a new legitimation crisis in the Czech Republic, one epitomised by an inability to establish universal support for neo-liberal capitalist accumulation as a sustainable path for political and economic reform. Although largely impressionistic in method, this exposition seeks to offer, with the aid of comparative analyses of other European cities, observations which provide insights that may benefit a broader empirical investigation and debate on residential experience, one that is enhanced by the interdisciplinary links between housing and tourism. More specifically, it explores the complex interrelationship between residential experience and tourism, arguing that the former illuminates a deeper understanding of the power relationships driving developmental processes-in this case, tourist-driven regeneration. In their determination to achieve compatibility with neo-liberal accumulation regimes, the post-communist governments of the Czech Republic appear to be neglecting, at the macro level, the broader social and environmental objectives of minimising social exclusion and protecting the nation's cultural heritage. It is too early to assess whether the new administration has recognised the need to realign policies closer to the traditional Czech value of political consensus. However, despite the creation of a distinct planning system within Prague, which recognises the emergence of a new 'income elite' alongside the 'socially weak', state-driven political and economic policies appear to be exacerbating these new social cleavages and creating the incipient signs of a 'clone city'. We suggest the need for an alternative vision of 'capitalism', one that enables the inclusion of a broad range of interests in decision-making, if Havel's dream of a 'civil society' is to be realised.
The Mass Media and the National Question in Udmurtia in the 1990s
Authors: Shkliaev Aleksandr , Toulouze Eva
Published: July 2002

The so-called “national,” or ethnopolitical questions, whose existence has long been denied in Russia, is a significant issue in the Udmurt Republic. The Soviet propaganda machine long advanced the theme of friendship among all the peoples of the multinational USSR until glasnost', when this notion began to be questioned by society. In the minority areas ethnic questions finally emerged at the end of the 1980s and since then have occupied a prominent place in the mass media, in Udmurtia and elsewhere. This article highlights the polemic character of the debate on ethnic issues in Udmurtia, which is located in the Volga-Urals region, against a background of the particular local historical and demographic factors.
‘Truth’ and ‘Lies’ Revisited
Authors: Sikes Pat
Published: July 2002

Anecdotal evidence suggests that many qualitative researchers have had the experience of discovering that their informants had told them lies. This is quite different to those instances where faulty memory, subjective perception, partial or erroneous knowledge, a desire to give the researcher what they think they want, or even where a ‘personal myth’ comes in to play, because a lie is a conscious and deliberate intention to deceive. What should researchers do when they discover that they have been misled? What are the implications for qualitative methodology and its practitioners in the light of the criteria for good practice outlined in the Tooley Report? This article draws on two examples of informants who lied, in order to explore some of the questions and issues that can arise. It suggests, tentatively, that generic criteria may not always be sufficiently sensitive to cope with complexities of social life.
Exploring reciprocal parent and child effects in the case of child inhibition in US and Korean samples
Authors: Belsky Jay , Rha Jong-Hay , Park Seong-Yeon
Published: July 2002

Recent research suggesting that parental behaviour may promote or discourage the development of inhibited behaviour stimulated interest in the effect of inhibited behaviour on parenting. Of 125 US 3-year-olds and 100 Korean 3-year-olds whose inhibited behaviour was evaluated repeatedly at age 3, the videotapes of the 50%most inhibited in each sample were rated with regard to parental responses that: (1) encouraged the child to approach the stimuli in question; (2) accepted and/or encouraged the child’s withdrawal; and (3) discouraged the child’s withdrawn behaviour. Analyses revealed that child effects on parenting were more pronounced than parenting effects on child behaviour; that mothers were more affected by child inhibition than fathers; that, surprisingly, parents who responded to child inhibition by accepting/encouraging child withdrawal also reacted by discouraging child withdrawal and encouraging approach; and that the greater the child’s inhibition, the more parents encouraged approach behaviour, encouraged/accepted withdrawal, and discouraged withdrawal. These results are discussed in terms of other evidence highlighting parental influences on child inhibition.
How and Why should We Write the History of Twentieth-Century Economics?
Authors: Backhouse Roger E.
Published: July 2002

Most discussions of how one should write the history of economics are conducted at a very abstract level. They debate the merits of alternative approaches without relating them to specific problem-situations or specific periods. The literature uses terms such as “absolutism,” “relativism,” “Whig history,” “thick history,” “historical reconstructions,” “rational reconstructions,” and “presentism,” frequently arguing that one of these approaches is better than one or more of the others. In warning historians of economics against sin, they typically define sin in absolute terms. This is particularly true of those who argue for “relativism,” “thick history,” “historical reconstructions” and the like. There is a simple reason for this. Terms such as “absolutism,” “Whig history,” and “presentism” all carry negative connotations, with the result that their advocates usually feel impelled to qualify them. On the other hand, supporters of “historical reconstruction,” “thick history” and so on feel much less pressure to offer such qualifications—the words used have the sound of “real” history. The terminology itself is value-laden.
Relationships Between Symbolic Play, Functional Play, Verbal And Non‐Verbal Ability In Young Children
Authors: Lewis Vicky , Boucher Jill , Lupton Laura , Watson Samantha
Published: July 2002

It is well established that certain aspects of play in young children are related to their emerging linguistic skills. The present study examined the relationships between functional play, symbolic play, non‐verbal ability, and expressive and receptive language in normally developing children aged between 1 and 6 years using standardized assessment procedures, including a recently developed Test of Pretend Play (ToPP). When effects of chronological age were partialled out, symbolic play remained significantly correlated with both expressive and receptive language, but not with functional play or non‐verbal ability; and functional play was only correlated significantly with expressive language. It is concluded that ToPP will provide practitioners with a useful way of assessing symbolic ability in children between the ages of 1 and 6 years, and will contribute to the assessment and diagnosis of a number of communication difficulties, and have implications for intervention.
Inactivation of Two Dictyostelium discoideum Genes, DdPIK1 and DdPIK2, Encoding Proteins Related to Mammalian Phosphatidylinositide 3-kinases, Results in Defects in Endocytosis, Lysosome to Postlysosome Transport, and Actin Cytoskeleton Organization
Authors: Buczynski Greg , Grove Bryon , Nomura Anson , Kleve Maurice , Bush John , Firtel Richard A. , Cardelli James
Published: July 2002

Phosphatidylinositide 3-kinases (PI 3-kinases) have been implicated in controlling cell proliferation, actin cytoskeleton organization, and the regulation of vesicle trafficking between intracellular organelles. There are at least three genes in Dictyostelium discoideum, DdPIK1, DdPIK2, and DdPIK3, encoding proteins most closely related to the mammalian 110-kD PI-3 kinase in amino acid sequence within the kinase domain. A mutant disrupted in DdPIK1 and DdPIK2 (Δddpik1/ddpik2) grows slowly in liquid medium. Using FITC-dextran (FD) as a fluid phase marker, we determined that the mutant strain was impaired in pinocytosis but normal in phagocytosis of beads or bacteria. Microscopic and biochemical approaches indicated that the transport rate of fluid-phase from acidic lysosomes to non-acidic postlysosomal vacuoles was reduced in mutant cells resulting in a reduction in efflux of fluid phase. Mutant cells were also almost completely devoid of large postlysosomal vacuoles as determined by transmission EM. However, Δddpik1/ddpik2 cells functioned normally in the regulation of other membrane traffic. For instance, radiolabel pulse-chase experiments indicated that the transport rates along the secretory pathway and the sorting efficiency of the lysosomal enzyme α-mannosidase were normal in the mutant strain. Furthermore, the contractile vacuole network of membranes (probably connected to the endosomal pathway by membrane traffic) was functionally and morphologically normal in mutant cells. Light microscopy revealed that Δddpik1/ddpik2 cells appeared smaller and more irregularly shaped than wild-type cells; 1–3% of the mutant cells were also connected by a thin cytoplasmic bridge. Scanning EM indicated that the mutant cells contained numerous filopodia projecting laterally and vertically from the cell surface, and fluorescent microscopy indicated that these filopodia were enriched in F-actin which accumulated in a cortical pattern in control cells. Finally, Δddpik1/ddpik2 cells responded and moved more rapidly towards cAMP. Together, these results suggest that Dictyostelium DdPIK1 and DdPIK2 gene products regulate multiple steps in the endosomal pathway, and function in the regulation of cell shape and movement perhaps through changes in actin organization.
The Localization of Bullous Pemphigoid Antigen 180 (BP180) in Hemidesmosomes Is Mediated by Its Cytoplasmic Domain and Seems to be Regulated by the β4 Integrin Subunit
Authors: Borradori Luca , Koch Peter J. , Niessen Carien M. , Erkeland Stefan , Leusden Manuel R. van , Sonnenberg Arnoud
Published: July 2002

Bullous pemphigoid antigen 180 (BP180) is a component of hemidesmosomes, i.e., cell-substrate adhesion complexes. To determine the function of specific sequences of BP180 to its incorporation in hemidesmosomes, we have transfected 804G cells with cDNA-constructs encoding wild-type and deletion mutant forms of human BP180. The results show that the cytoplasmic domain of BP180 contains sufficient information for the recruitment of the protein into hemidesmosomes because removal of the extracellular and transmembrane domains does not abolish targeting. Expression of chimeric proteins, which consist of the membrane targeting sequence of K-Ras fused to the cytoplasmic domain of BP180 with increasing internal deletions or lacking the NH2 terminus, indicates that the localization of BP180 in hemidesmosomes is mediated by a segment that spans 265 amino acids. This segment comprises two important regions located within the central part and at the NH2 terminus of the cytoplasmic domain of BP180.

To investigate the effect of the α6β4 integrin on the subcellular distribution of BP180, we have transfected COS-7 cells, which lack α6β4 and BP180, with cDNAs for BP180 as well as for human α6A and β4. We provide evidence that a mutant form of BP180 lacking the collagenous extracellular domain as well as a chimeric protein, which contains the entire cytoplasmic domain of BP180, are colocalized with α6β4. In contrast, when cells were transfected with cDNAs for α6A and mutant forms of β4, either lacking the cytoplasmic COOH-terminal half or carrying phenylalanine substitutions in the tyrosine activation motif of the cytoplasmic domain, the recombinant BP180 molecules were mostly not colocalized with α6β4, but remained diffusely distributed at the cell surface. Moreover, in cells transfected with cDNAs for α6A and a β4/β1 chimera, in which the cytoplasmic domain of β4 was replaced by that of the β1 integrin subunit, BP180 was not colocalized with the α6β4/β1 chimera in focal adhesions, but remained again diffusely distributed. These results indicate that sequences within the cytoplasmic domain of β4 determine the subcellular distribution of BP180.
A Role for Cdk2 Kinase in Negatively Regulating DNA Replication during S Phase of the Cell Cycle
Authors: Hua Xuequn Helen , Yan Hong , Newport John
Published: July 2002

Using cell-free extracts made from Xenopus eggs, we show that cdk2-cyclin E and A kinases play an important role in negatively regulating DNA replication. Specifically, we demonstrate that the cdk2 kinase concentration surrounding chromatin in extracts increases 200-fold once the chromatin is assembled into nuclei. Further, we find that if the cdk2–cyclin E or A concentration in egg cytosol is increased 16-fold before the addition of sperm chromatin, the chromatin fails to initiate DNA replication once assembled into nuclei. This demonstrates that cdk2–cyclin E or A can negatively regulate DNA replication. With respect to how this negative regulation occurs, we show that high levels of cdk2–cyclin E do not block the association of the protein complex ORC with sperm chromatin but do prevent association of MCM3, a protein essential for replication. Importantly, we find that MCM3 that is prebound to chromatin does not dissociate when cdk2– cyclin E levels are increased. Taken together our results strongly suggest that during the embryonic cell cycle, the low concentrations of cdk2–cyclin E present in the cytosol after mitosis and before nuclear formation allow proteins essential for potentiating DNA replication to bind to chromatin, and that the high concentration of cdk2–cyclin E within nuclei prevents MCM from reassociating with chromatin after replication. This situation could serve, in part, to limit DNA replication to a single round per cell cycle.
Differentiation and Death of Premyelinating Oligodendrocytes in Developing Rodent Brain
Authors: Trapp Bruce D. , Nishiyama Akiko , Cheng David , Macklin Wendy
Published: July 2002

Previous studies have indicated that newly formed oligodendrocytes are dynamic cells whose production, survival, and differentiation depend upon axonal influences. This study has characterized the appearance and fate of newly formed oligodendrocytes in developing rat brain. Oligodendrocytes appear in predictable locations and radially extend DM-20–positive processes that cover 80-μm domains in the cortex and 40-μm domains in the corpus callosum. These premyelinating oligodendrocytes have one of two fates: they myelinate axons or degenerate. Between 7 and 21 d after birth, ∼20% of premyelinating oligodendrocytes identified in the cerebral cortex were degenerating. Oligodendrocytes that ensheathed axons expressed and selectively targeted proteolipid protein to compact myelin and did not degenerate. These observations support the hypothesis that axonal influences affect oligodendrocyte survival, differentiation, and expression of proteolipid protein gene products.
Involvement of ZO-1 in Cadherin-based Cell Adhesion through Its Direct Binding to α Catenin and Actin Filaments
Authors: Itoh Masahiko , Nagafuchi Akira , Moroi Seiji , Tsukita Shoichiro
Published: July 2002

ZO-1, a 220-kD peripheral membrane protein consisting of an amino-terminal half discs large (dlg)-like domain and a carboxyl-terminal half domain, is concentrated at the cadherin-based cell adhesion sites in non-epithelial cells. We introduced cDNAs encoding the full-length ZO-1, its amino-terminal half (N-ZO-1), and carboxyl-terminal half (C-ZO-1) into mouse L fibroblasts expressing exogenous E-cadherin (EL cells). The full-length ZO-1 as well as N-ZO-1 were concentrated at cadherin-based cell–cell adhesion sites. In good agreement with these observations, N-ZO-1 was specifically coimmunoprecipitated from EL transfectants expressing N-ZO-1 (NZ-EL cells) with the E-cadherin/α, β catenin complex. In contrast, C-ZO-1 was localized along actin stress fibers. To examine the molecular basis of the behavior of these truncated ZO-1 molecules, N-ZO-1 and C-ZO-1 were produced in insect Sf9 cells by recombinant baculovirus infection, and their direct binding ability to the cadherin/catenin complex and the actin-based cytoskeleton, respectively, were examined in vitro. Recombinant N-ZO-1 bound directly to the glutathione-S-transferase fusion protein with α catenin, but not to that with β catenin or the cytoplasmic domain of E-cadherin. The dissociation constant between N-ZO-1 and α catenin was ∼0.5 nM. On the other hand, recombinant C-ZO-1 was specifically cosedimented with actin filaments in vitro with a dissociation constant of ∼10 nM. Finally, we compared the cadherin-based cell adhesion activity of NZ-EL cells with that of parent EL cells. Cell aggregation assay revealed no significant differences among these cells, but the cadherin-dependent intercellular motility, i.e., the cell movement in a confluent monolayer, was significantly suppressed in NZ-EL cells. We conclude that in nonepithelial cells, ZO-1 works as a cross-linker between cadherin/catenin complex and the actin-based cytoskeleton through direct interaction with α catenin and actin filaments at its amino- and carboxyl-terminal halves, respectively, and that ZO-1 is a functional component in the cadherin-based cell adhesion system.