bluuebunny/crossref_metadata_2025 huggingface dataset:
KCNQ4, a K
+
channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway
Authors: Kharkovets Tatjana , Hardelin Jean-Pierre , Safieddine Saaid , Schweizer Michaela , El-Amraoui Aziz , Petit Christine , Jentsch Thomas J.
Published: July 2002

Mutations in the potassium channel gene
KCNQ4
underlie DFNA2, an autosomal dominant form of progressive hearing loss in humans. In the mouse cochlea, the transcript has been found exclusively in the outer hair cells. By using specific antibodies, we now show that KCNQ4 is situated at the basal membrane of these sensory cells. In the vestibular organs, KCNQ4 is restricted to the type I hair cells and the afferent calyx-like nerve endings ensheathing these sensory cells. Several lines of evidence suggest that KCNQ4 underlies the
I
K,n
and
g
K,L
currents that have been described in the outer and type I hair cells, respectively, and that are already open at resting potentials. KCNQ4 is also expressed in neurons of many, but not all, nuclei of the central auditory pathway, and is absent from most other brain regions. It is present, e.g., in the cochlear nuclei, the nuclei of the lateral lemniscus, and the inferior colliculus. This is the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of KCNQ4 in the mouse auditory system raises the possibility of a central component in the DFNA2 hearing loss.
Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D
1
antagonists
Authors: Ciccocioppo Roberto , Sanna Pietro Paolo , Weiss Friedbert
Published: July 2002

The conditioning of cocaine's subjective actions with
environmental stimuli may be a critical factor in long-lasting relapse
risk associated with cocaine addiction. To study the significance of
learning factors in persistent addictive behavior as well as the
neurobiological basis of this phenomenon, rats were trained to
associate discriminative stimuli (S
D
) with the availability
of i.v. cocaine vs. nonrewarding saline solution, and then placed on
extinction conditions during which the i.v. solutions and
S
D
s were withheld. The effects of reexposure to the
S
D
on the recovery of responding at the previously
cocaine-paired lever and on Fos protein expression then were determined
in two groups. One group was tested immediately after extinction,
whereas rats in the second group were confined to their home cages for
an additional 4 months before testing. In both groups, the cocaine
S
D
, but not the non-reward S
D
, elicited strong
recovery of responding and increased Fos immunoreactivity in the
basolateral amygdala and medial prefrontal cortex (areas
Cg1/Cg3). The response reinstatement and Fos expression induced
by the cocaine S
D
were both reversed by selective
dopamine D
1
receptor antagonists. The undiminished
efficacy of the cocaine S
D
to elicit drug-seeking behavior
after 4 months of abstinence parallels the long-lasting nature of
conditioned cue reactivity and cue-induced cocaine craving in
humans, and confirms a significant role of learning factors in the
long-lasting addictive potential of cocaine. Moreover, the results
implicate D
1
-dependent neural mechanisms within the
medial prefrontal cortex and basolateral amygdala as
substrates for cocaine-seeking behavior elicited by cocaine-predictive
environmental stimuli.
Psychological adjustment to cancer in a collective culture
Authors: Sun Lina N.N. , Stewart Sunita Mahtani
Published: July 2002

We examined the associations between social support, health locus of control, neuroticism, and psychological adjustment (PA) in 152 Hong Kong Chinese patients. Our objective was to assess hypotheses relevant to the cohesive family structure, and the belief in external sources of control that pervade this culture. Use of social support by individuals who reported reliable support, and internal locus of control (ILOC) associated positively, and neuroticism associated negatively with PA. The independent variables accounted for up to 39% of the variance in PA measures. Our findings provide rare information about coping with serious illness in a non‐Western culture. They illustrate the centrality of family relationships in Chinese culture. They suggest that even in a culture where supernatural beliefs are widespread, ILOC relates positively and “chance” beliefs relate negatively to adjustment. Finally they support the importance of controlling for neuroticism in examining stress.
The Geography of Residential Turnover in Twenty-seven Large US Metropolitan Housing Markets, 1985-95
Authors: Dieleman Frans M. , Clark William A. V. , Deurloo Marinus C.
Published: July 2002

Previous research on variations in mobility rates across metropolitan areas, documented the link between immigration and local mobility, and the way in which local mobility creates 'hot' and 'cold' housing markets. The research in this paper confirms and extends those analyses by examining the interplay between the relocation process and the structure of metropolitan housing markets. The results show that more than three-quarters of the turnover is generated by renters and most of this by households under 35 years of age. It also shows that variations in mobility rates can be predicted by variations in new construction, though it is clear that ultimately it is the underlying population growth which is the critical variable. House prices also vary across metropolitan areas and are influenced by city size, but the major determinants of variation in house prices are household income (a measure of upward pressure on prices) and the tenure structure of the local market. The results show that turnover per se is at least as important as price in creating opportunities for tenure change and residential relocation.
A New Approach to Neighbourhood Renewal in England
Authors: Wallace Moira
Published: July 2002

This paper summarises the comprehensive approach to tackling the problems of poor neighbourhoods developed by the British government's Social Exclusion Unit (SEU). It analyses neighbourhood decline and why it has occurred, and describes the SEU's National Strategy for Neighbourhood Renewal, which is focused on improving public services in England, building inclusive partnerships locally that focus on community needs and using new data to target help where it is most needed. It shows how the strategy is based on proven initiatives and underpinned with significant new funding.
Development Rights Markets to Manage Urban Plans in Italy
Authors: Micelli Ezio
Published: July 2002

Urban economists and planners have been debating the possibility of using innovative methods and tools in managing urban plans to increase their effectiveness. According to many theoretical contributions, a major step would lie in shifting from the use of authoritative tools towards market-based ones. The institution of a development rights market in order to implement urban plans represents a major attempt to transfer into the practical urban government such a theoretical perspective. Several significant elements emerge from an analysis of the major case studies of development rights markets in Italy. First, markets for development rights do not replace the command-and-control tools traditionally used in planning. In reality, the success of the new markets seems to depend significantly on their integration with the latter. Furthermore, markets for development rights have not proved to be automatic devices led by an invisible hand: the visible hands of the administrations take steps to establish market rules and to promote them, reducing transaction costs as much as possible.
The Czech Housing System in the Middle of Transition
Authors: Musil Jiri
Published: July 2002

This paper critically evaluates the changes in the housing system and housing policies of the Czech Republic after 1989. The dismantling of the old socialist housing system, part of a more general transformation of Czech society, is shown to have been guided in the first instance by the belief that the introduction of a market model would create a balanced housing economy. The subsequent failure of this approach has led to the adoption of more pragmatic housing policies which have been developed in conjunction with continued efforts to establish a housing finance system. The paper concludes that the housing needs of low-income households require the introduction of new forms of affordable social housing.
Market Activity and Industrial Development
Authors: Adams C.D. , Russell L. , Taylor-Russell C.S.
Published: July 2002

Most models of the development process concentrate on either events, agencies or the structural framework for development. Such models encourage simplistic policy responses to perceived development constraints. This paper explores the actions, interests and strategies of those who own land with potential for industrial development within the context of the resources to which they have access, the rules that they consider govern their behaviour and the ideas that they draw upon in land management and development. It is suggested that while active landowners may welcome or indeed initiate industrial development, passive owners can undermine development potential. The paper is based on research into the development achievements or prospects of 120 industrial sites in North West England.
Determinants of Bargaining Outcome in Single-family Housing Transactions: An Empirical Examination
Authors: Song Shunfeng
Published: July 2002

Using a hedonic regression model, this paper examines determinants of bargaining outcome in single-family housing transactions. It divides potential factors into three broad categories: dwelling attributes, site amenities, and seller's and buyer's characteristics. Results with use of 1990 data for the Reno-Sparks area in Nevada show that bargaining outcome is determined by seller's asking price, buyer's household income, and some of the dwelling attributes and site amenities. This paper concludes that factors affecting housing price do not necessarily affect bargaining outcome, and first-time home buyers do not statistically bargain less than repeat home buyers.
The Residential Mobility of Ethnic Minorities: A Longitudinal Analysis
Authors: Bonvalet Catherine , Carpenter Juliet , White Paul
Published: July 2002

Studies of ethnic minority settlement in major cities usually depend upon snapshot evidence derived from periodic population censuses. The objects of such research are usually city regions, neighbourhoods or census tracts, and changes through time can not be undertaken as process studies but only as comparisons between given dates. In discussing the residential mobility experiences of ethnic minority populations it would be extremely valuable to be able to use individuals as the research units instead of geographical areas. This possibility exists for the study of ethnic minority residential mobility in the Paris region through the secondary analysis of a major survey carried out in 1986 by the French National Demographic Research Institute (INED). The results of such an analysis lead to a questioning of certain established ideas on the importance of the inner city for residence, but provide confirmation of higher-than-average mobility rates.
China's Urban Development: A Case Study of Luoyang and Guiyang
Authors: Hsu Mei-Ling
Published: July 2002

The growth of Chinese cities is often explained by their industrial development. This study relates city growth instead to the 1950s and later government urban directives and the economic policies of the pre-reform era which emphasised heavy industries. These government actions are examined locally, in Guiyang and Luoyang; both cities are ranked low by socio-economic indices. This study reveals that government directives have shaped the functions and land use of the two cities and are the sources of some of the cities' current problems. Indeed, once the economic structure of a city was determined, it was difficult to change. The study also shows that the more rapid population increase of Luoyang is due to its high rate of natural increase as well as its industrial development. A broad approach that considers both common influences and unique local conditions is required in the analysis of Chinese urban development.
Intra-urban Spatial Analysis of Housing-related Urban Policies: The Case of Liverpool, 1981-91
Authors: Tang Zilai , Batey Peter W. J.
Published: July 2002

This paper presents a case study of Liverpool focusing on the transformation of the urban landscape associated with housing development. After examining different types of housing development with reference to housing policy initiatives and their underlying processes at various levels, the paper identifies some contrasting features of urban spatial transformation. First, this transformation is characterised by the city-wide spread of socio-economic downgrading caused by private de-investment in the production sphere, in contrast to the pockets of socio-economic upgrading resulting from private investment (on the urban fringe) and reinvestment (on the waterfront) in the consumption sphere. Secondly, the city has witnessed significant residential improvement (especially in the inner city) due to its success in securing public resource allocation, in contrast to economic devastation illustrating its increasing marginalisation in the movement of private investment.
The Housing Challenge in South Africa
Authors: Goodlad Robina
Published: July 2002

This paper considers the housing conditions inherited by the new government in South Africa and the challenge they present. It draws on primary and secondary sources, and on interviews with some of the key actors involved in housing policy. It examines contemporary housing conditions, and the colonial and apartheid legacy which largely created them. It goes on to consider the implications of the struggle under apartheid for improvements in living conditions, and to review developments in housing policy in the 1980s and early 1990s. The policies emerging from the first year of the new government are described, and the implementation of policy in the first two years is reviewed. Issues that arise are discussed, and the conditions required for the state, market and civil society to play their part in achieving the objectives of housing policy are considered.
Structures Investment and Economic Growth: A Long-term International Comparison
Authors: Ball Michael , Morrison Tanya , Wood Andrew
Published: July 2002

Interest has grown again in recent years about the long-term and cyclical nature of building investment and its effect on the macroeconomy. This paper investigates the nature of building trends and cycles from the 19th century to the present day for eight major OECD economies. Focusing predominantly on non-housing structures, the Kalman filter is used to decompose the series into trends and cycles. It was found that building cycles exist in all countries, though with considerable variation. Comparisons of volatility between countries and between the different types of fixed investment are made. The long-run share of fixed investment in structures as a proportion of national income is investigated. Consideration is given to whether international building investment trends are coincident, and an analysis made of the long-term correlation between structures investment cycles.
The Differential Incidence of an Urban Land Tax Depends on the Travel Intensities of Substitutes for Land
Authors: Bentick Brian L.
Published: July 2002

There is an extensive literature on the incidence of the real property tax. In 1990 Pasha considered the incidence of an exclusive tax on urban land rents. He concluded that such a tax would initially impact on consumers of housing, but that the changes in spending induced by the tax would cause its burden to be shared between consumers and landowners according to the elasticity of substitution between land and other market goods, and the location of the land with respect to the urban margin. This note shows that, in order to impose any burden on consumers, the urban land tax needs to be supplemented by planning controls to prevent consumers on the urban margin shifting to the rural area in order to escape the tax. It also shows that the incidence of the tax between consumers and owners of intra-marginal land depends on the 'travel intensity' of the goods which are favoured by its substitution effects, and that these need to be specified.
From 'Soviet' to 'European' Yaroslavl: Changing Neighbourhood Structure in Post-Soviet Russian Cities
Authors: Goodrich Lehmann Susan , Ruble Blair A.
Published: July 2002

The absence of a market meant that Soviet cities evolved in fundamentally different ways from Western cities, but economic reform promises to transform them. Drawing from 1993 survey data from the city of Yaroslavl, the paper analyses how Russian citizens look at their Soviet-made city. It finds that Russians of diverse background appear to be drawn to a historically `European' model of urban development in which the central city becomes home to the monied class and the socially correct, while poorer social groups are pushed toward the periphery. To understand the dynamics of the early stages of post-Soviet city development, a regression model containing demographic, life-stage and housing-condition variables is developed which predicts 52 per cent of the variance in moving intentions. After describing the initial impact of the housing privatisation process, the paper examines the reasons behind and the significance of the precipitous decline in housing privatisation since 1993.
Splintering Networks: Cities and Technical Networks in 1990s Britain
Authors: Guy Simon
Published: July 2002

The past 15 years have seen an enormous shift in the regulation and management of infrastructure networks in the UK. Complex patchworks of competitive gas, electricity, water and telecom providers are replacing the relatively uniform, monopolistic and monolithic regimes of the post-war period. These changes have major, but poorly explored, implications for the economic, social and environmental development of British cities. In this context, the current paper aims critically to problematise the conventional approach of urban analysts to the development of urban technical networks. We do this in four parts. First, we develop a sympathetic critique of existing conceptual approaches to the study of urban technical networks. Secondly, we analyse the transformation of urban technical systems in the UK since the implementation of the Conservatives' privatisation process of the 1980s. In particular, we focus on the 'splintering' of infrastructure networks and the creation of complex new 'patchworks' of urban technical systems. Thirdly, we build upon this analysis to identify the social, economic and environmental logics emerging from this process of rapid change. Finally, we draw together the implications of the splintering process for the governance of British cities.
Upper-middle-class Influence on Developmental Policy Outcomes: The Case of Transit Infrastructure
Authors: Boschken Herman L.
Published: July 2002

Past research on urban economic development has targeted three major lines of inquiry on determinants of policy outcomes. One focuses on the power of political actors engaged in agency processes. Another looks at institutional structure and the third emphasises physical and social 'preconditions' of urban structure. Although heavily researched, none of these approaches has produced conclusive empirical results. In part, this may be due to the research being nearly void of inquiry into the issue of 'indirect social influence'. This paper probes the thesis that variance in economic development outcomes is determined in part by agencies perceiving anonymous publics where no direct interaction is involved. It examines this with reference to an upper-middle-class lifestyle. Using infrastructure investment of 42 transit agencies across the US, regression results show a UMC factor to be more significant in explaining differences in policy outcomes than those of traditional rival theses. The paper concludes with an inferential analysis of why and how such indirect influence might occur.
Geographical Barriers to Employment for American-born and Immigrant Workers
Authors: Preston Valerie , McLafferty S. , Liu X.F.
Published: July 2002

Residential segregation interacts with the changing geography of transport and employment in urban areas to restrict access to workplaces. A growing literature suggests that spatial barriers limit the job opportunities of minority women and men in American cities. This study examines the nature and extent of geographical barriers for minority immigrants by analysing their commuting behaviour. Information from the 1990 Public Use Microdata Sample is used to compare the commuting times of immigrant and native-born minority women in central parts of the New York Consolidated Metropolitan Statistical Area. The effects of occupation, wages, family responsibilities, transport mode, year of arrival in the US and English fluency on commuting time are assessed separately for immigrant men and women. The results suggest that race/ethnic group has a larger influence on commuting times than place of birth. However, white immigrant women's employment is less restricted by geographical barriers than that of minority immigrants. The findings confirm the diversity of immigrant women's experiences, reinforcing the need to consider the interrelations among gender, race and class when examining urban labour markets.
The New Structure of Building Provision and the Transformation of the Urban Landscape in Metropolitan Guangzhou, China
Authors: Fulong Wu
Published: July 2002

This study considers recent changes in the built environment of Chinese metropolitan areas during the transition from a planned to a market economy. Implications of this transition include changes in the political economy (increasing localisation, diversification of investment and the growth of foreign capital), in the organisation of urban and land development (from project-specific to comprehensive development and real estate development) and in the functions of urban planning (from a sectoral-subordinated to a municipally based control). The imprints of these changes on the built environment are illustrated with reference to the example of metropolitan Guangzhou. Among the new elements identified here are the landscapes of the new business district, gentrified residential communities, new social areas, urban sprawl, large peripheral residential communities and development zones and sub-centres.
Scientific Centres in Europe: An Analysis of Research Strength and Patterns of Specialisation Based on Bibliometric Indicators
Authors: Wichmann Matthiessen Christian n , Winkel Schwarz Annette
Published: July 2002

This paper presents the first analysis of scientific strength by output (papers in the Science Citation Index 1994-96) produced by authors from the 'greater' urban regions of Europe. Top lists of European centres are indicated. Four agglomerations constitute the European super-league of science: London, Paris, Moscow and the Dutch urban agglomeration of Amsterdam, the Hague, Rotterdam and Utrecht. The next layer could be named the primary league and comprises 19 large research centres. A third group of 16 cities forms a secondary league of 16 smaller research centres. These upper-level research strongholds are categorised in the paper where patterns of specialisations by absolute and relative distribution of research disciplines for each city are identified and families of cities by research pattern are analysed and compared within the perspective of urban economic growth and change.
Governmentality and 'the Death of the Social'?: A Discourse Analysis of Local Government Texts in South-east England
Authors: Stenson Kevin , Watt Paul
Published: July 2002

Writers from within the Foucauldian govern mentality school have characterised recent governmental trends, associated with neo-liberal political rationalities, as manifestations of the death of the collectivist and universalist character of the 'social'. However, the unfolding of these developments varies both between and within nation-states. Drawing upon a discourse analysis of two local government texts from a local authority district in south-east England, the paper emphasises that at this local level the 'social' is reformulated rather than displaced in the way that the grand narrative of the 'decline of the social' implies. In both documents, albeit in different ways, neo-liberal discourse operates in tension with a continuing emphasis upon appearing to maintain equitable and universally legitimate service provision. This amounts not to the death, but rather to a reformulation, of the social.
Natural Governance and the Governance of Nature: The Hazards of Natural Law Feminism
Authors: Ruhl Lealle
Published: July 2002

This article examines the precepts of natural law feminism, and in exploring the writings of two Canadian feminists, Maureen McTeer and Louise Vandelac, examines how natural law feminism is deployed in debates about how to theorize reproduction. I contend that the natural law perspective obscures many issues worthy of feminist inquiry, and, perhaps more critically, eschews a discourse that emphasizes reproductive freedom in favour of one which has at its centre a largely unproblematized view of reproduction that follows a biologically driven script of conception, gestation, childbirth and mothering as inherently and necessarily connected.

I argue that this stance is particularly evident in natural law feminist analyses of ecology and the regulation of new reproductive and genetic technologies. In both these areas, natural law feminism poses the central problem as one in which feminists must zealously protect the natural association between women and reproduction; in so doing, natural law feminists gloss over the nature of this association. I suggest a reframing of the focus of debates on reproduction from what is natural and what is socially constructed to how we demarcate the two.
Violence and Violation: Women and Secure Settings1
Authors: Aitken Gill , Women Kate Noble
Published: July 2002

This article focuses on service provision for women who are involuntarily referred under the UK Mental Health Act (1983) into medium and high security care in England and Wales. We explore how physical and procedural security in such settings is prioritized over relational care (see also Fallon Report, Department of Health, 1999a and NHS Executive, 2000 – Tilt Report). We are not arguing against the importance of protecting the public from the acts of dangerous members of our society. However, we are arguing that many of the women in our secure services are inappropriately placed and receive inappropriate forms of treatment and care. Rather than physical security, it is high relational care, which the women require. Further, we argue that current service provision often re-produces forms of violence and violation which have marked many of women's lives prior to their entry into the secure system.
Correlates of psychological well-being at midlife: The role of generativity, agency and communion, and narrative themes
Authors: Grossbaum Miriam F. , Bates Glen W.
Published: July 2002

This study examined the correlates of well-being at midlife in 49 midlife adults. Self-report measures of generativity, agency and communion, along with relevant themes taken from narratives were considered as predictors of Ryff’s multidimensional model of well-being and of life satisfaction. Multiple regressions identified generative concern as a predictor of the six well-being dimensions and of life satisfaction. A separate series of multiple regressions identified narrative themes of contamination, redemption, and affect tone as predictors of four of the well-being dimensions and of life satisfaction. Hierarchical regression analyses controlling for self-report measures showed contamination to be a significant predictor of environmental mastery, personal growth, and life satisfaction. Affect tone was a predictor of self-acceptance and life satisfaction. This pattern of results was not influenced by the inclusion of demographic factors. Overall, the findings indicate the utility of combining narrative data with self-report data in investigating well-being at midlife.
Individual and Family Factors Contributing to Mothers’ and Fathers’ Positive Parenting
Authors: Russell Alan
Published: July 2002

Individual and family factors contributing to harsh parenting have been investigated, but little is known of how comparable factors contribute to positive parenting. In the study reported, the contributions to positive parenting of parent positive personality qualities, positive child characteristics, and marital quality were investigated in a middle class sample of intact families in which the eldest child was 6-7 years of age. A positive parenting composite was formed by summing measures relating to self-reported positive involvement with the child, observed warmth/affection, and observed positive involvement. Moderate associations were found between positive parenting and the predictor variables, with these significant for mothers but not for fathers. The absence of associations for father variables occurred in both father-son and father-daughter dyads. The most consistent predictions were in the mother-son dyad. Therefore, whereas factors contributing to positive parenting were identified, gender differences were suggested by the findings.
Action-control Beliefs and School Performance: A Longitudinal Study of Moscow Children and Adolescents
Authors: Little Todd D. , Stetsenko Anna , Maier Heiner
Published: July 2002

In a longitudinal sample of Moscow children and adolescents (grades 2-11; n = 434, tested in 1990, 1992, and 1994), we examined the interrelations between their action-control beliefs about school performance and their actual school performance. A notable feature of this sample is that the students were exposed to an educational context that is relatively stable and consistent across the elementary and secondary school years. This feature provided us with a rare opportunity to study developmental changes that are relatively free of the pronounced context changes typically associated with the transition to adolescence (e.g. in the United States). The developmental trends of the action-control beliefs showed much continuity and cross-cultural generality, mostly extending age-related trends based on elementary-aged children. On the other hand, some of the trajectories showed evidence of distinct changes associated with the transition to adolescence. For example, although the participants’ beliefs in their own ability showed a steady increase throughout childhood and adolescence, both: (a) their beliefs in their own effort and the accessibility of teachers and luck; and (b) their general control-expectancy decreased throughout childhood and adolescence. In addition, a consistent and reciprocal cross-time pattern of predictive effects between beliefs and performance emerged, with beliefs about personal ability being associated with changes in subsequent performance and vice versa. Given the few longitudinal studies and inconsistent findings in the field, the outcomes of this study shed new light on the dynamics of action-control development and strongly support the idea that beliefs about one’s own action potential and actual performance form a synergistic and dynamic system of reciprocal effects.
Stability of Genetic and Environmental In‘uences on Reading Performance at 7 and 12 Years of Age in the Colorado Adoption Project
Authors: Wadsworth S. J. , Fulker D. W. , DeFries J. C.
Published: July 2002

Results obtained from longitudinal studies suggest that individual differences in reading performance are relatively stable over time. However, the aetiology of this stability has not been previously explored. In the current study, the aetiology of longitudinal stability of reading performance between 7 and 12 years of age was assessed using data from adoptive (97 unrelated sibling pairs at age 7 and 73 pairs at age 12) and nonadoptive (106 related pairs at age 7 and 75 pairs at age 12) children tested in the Colorado Adoption Project. Results of a bivariate behavioural genetic analysis confirmed earlier findings of moderate genetic influence on individual differences in reading performance at both 7 and 12 years of age ( h2 = .49 and .37, respectively). Moreover, about 70% of the observed stability ( r = .61) between the two ages was due to common genetic influences. Of special interest, no new heritable or shared environmental variation was manifested at age 12, suggesting that the same genetic and shared environmental influences were operating at both ages. In contrast, nonshared environmental influences (e.g. instructional methods, teachers, peers, etc.) were responsible for change between 7 and 12 years of age, indicating the salience of such factors for the development of reading performance between middle childhood and adolescence.
Innovation through Knowledge Codification
Authors: Sørensen Carsten , Lundh-Snis Ulrika
Published: July 2002

Academics and business professionals are currently showing a significant interest in understanding the management of knowledge and the roles to be played therein by information and communication technology (ICT). This paper takes a closer look at one of the primary issues raised when supporting the management of knowledge: how to understand the role of knowledge classification and codification as means for further organizational learning and innovation. Two manufacturing cases are analysed using particular perspectives from current theories on classification, namely the management of knowledge and organizational innovation. It is concluded that a more complex understanding of the interplay between cognitive and community models for knowledge management as informed by research on the social processes of classification can inform our understanding of both the role of classification of knowledge for organizational innovation and the viability of providing ICT support based on codified knowledge.
Socio‐economic aspects of areca nut use
Authors: Croucher R. , Islam S.
Published: July 2002

Abstract The socio‐economic aspects of areca nut consumption have been overlooked. A narrative review was conducted to establish some of these features of areca nut consumption. Medline, Pubmed and the World Wide Web were searched using the terms: areca nut, betel nut, areca catechu and pan masala. Further analysis was conducted of datasets describing aspects of United Kingdom areca nut sales and consumption. South Asian economies at different stages of development have varying areca nut cultivation practices, employment opportunities and marketing strategies. Attempts at regulation of areca nut import and sales are described. Retail practice among the South Asian communities of the United Kingdom was found to reflect the diverse consumer practices current in their countries of origin. A study of areca nut consumption patterns and motivations among Bangladeshi women resident in East London identified differences between those chewing areca nut in paan with and without tobacco. Further research into the socio‐economic aspects of areca nut consumption is needed which should be multidisciplinary in focus, of sound scientific quality and incorporating the opinions of consumers.
The Protozoan Parasite Toxoplasma gondii Targets Proteins to Dense Granules and the Vacuolar Space Using Both Conserved and Unusual Mechanisms
Authors: Karsten Verena , Qi Huilin , Beckers Con J.M. , Reddy Anita , Dubremetz Jean-Francois , Webster Paul , Joiner Keith A.
Published: July 2002

All known proteins that accumulate in the vacuolar space surrounding the obligate intracellular protozoan parasite Toxoplasma gondii are derived from parasite dense granules. To determine if constitutive secretory vesicles could also mediate delivery to the vacuolar space, T. gondii was stably transfected with soluble Escherichia coli alkaline phosphatase and E. coli β-lactamase. Surprisingly, both foreign secretory reporters were delivered quantitatively into parasite dense granules and efficiently secreted into the vacuolar space. Addition of a glycosylphosphatidylinositol membrane anchor rerouted alkaline phosphatase to the parasite surface. Alkaline phosphatase fused to the transmembrane domain and cytoplasmic tail from the endogenous dense granule protein GRA4 localized to dense granules. The protein was secreted into a tuboreticular network in the vacuolar space, in a fashion dependent upon the cytoplasmic tail, but not upon a tyrosine-based motif within the tail. Alkaline phosphatase fused to the vesicular stomatitis virus G protein transmembrane domain and cytoplasmic tail localized primarily to the Golgi, although staining of dense granules and the intravacuolar network was also detected; truncating the cytoplasmic tail decreased Golgi staining and increased delivery to dense granules but blocked delivery to the intravacuolar network. Targeting of secreted proteins to T. gondii dense granules and the plasma membrane uses general mechanisms identified in higher eukaryotic cells but is simplified and exaggerated in scope, while targeting of secreted proteins beyond the boundaries of the parasite involves unusual sorting events.
A Membrane Coat Complex Essential for Endosome-to-Golgi Retrograde Transport in Yeast
Authors: Seaman Matthew N.J. , Michael McCaffery J. , Emr Scott D.
Published: July 2002

We have recently characterized three yeast gene products (Vps35p, Vps29p, and Vps30p) as candidate components of the sorting machinery required for the endosome-to-Golgi retrieval of the vacuolar protein sorting receptor Vps10p (Seaman, M.N.J., E.G. Marcusson, J.-L. Cereghino, and S.D. Emr. 1997. J. Cell Biol. 137:79–92). By genetic and biochemical means we now show that Vps35p and Vps29p interact and form part of a multimeric membrane-associated complex that also contains Vps26p, Vps17p, and Vps5p. This complex, designated here as the retromer complex, assembles from two distinct subcomplexes comprising (a) Vps35p, Vps29p, and Vps26p; and (b) Vps5p and Vps17p. Density gradient fractionation of Golgi/endosomal/vesicular membranes reveals that Vps35p cofractionates with Vps5p/Vps17p in a vesicle-enriched dense membrane fraction. Furthermore, gel filtration analysis indicates that Vps35p and Vps5p are present on a population of vesicles and tubules slightly larger than COPI/coatomer-coated vesicles. We also show by immunogold EM that Vps5p is localized to discrete regions at the rims of the prevacuolar endosome where vesicles appear to be budding. Size fractionation of cytosolic and recombinant Vps5p reveals that Vps5p can self-assemble in vitro, suggesting that Vps5p may provide the mechanical impetus to drive vesicle formation. Based on these findings we propose a model in which Vps35p/Vps29p/Vps26p function to select cargo for retrieval, and Vps5p/Vps17p assemble onto the membrane to promote vesicle formation. Conservation of the yeast retromer complex components in higher eukaryotes suggests an important general role for this complex in endosome-to-Golgi retrieval.
Arginase II Downregulates Nitric Oxide (NO) Production and Prevents NO-mediated Apoptosis in Murine Macrophage-derived RAW 264.7 Cells
Authors: Gotoh Tomomi , Mori Masataka
Published: July 2002

Excess nitric oxide (NO) induces apoptosis of some cell types, including macrophages. As NO is synthesized by NO synthase (NOS) from arginine, a common substrate of arginase, these two enzymes compete for arginine. There are two known isoforms of arginase, types I and II. Using murine macrophage-like RAW 264.7 cells, we asked if the induction of arginase II would downregulate NO production and hence prevent apoptosis. When cells were exposed to lipopolysaccharide (LPS) and interferon-γ (IFN-γ), the inducible form of NOS (iNOS) was induced, production of NO was elevated, and apoptosis followed. When dexamethasone and cAMP were further added, both iNOS and arginase II were induced, NO production was much decreased, and apoptosis was prevented. When the cells were transfected with an arginase II expression plasmid and treated with LPS/IFN-γ, some cells were rescued from apoptosis. An arginase I expression plasmid was also effective. On the other hand, transfection with the arginase II plasmid did not prevent apoptosis when a NO donor SNAP or a high concentration (12 mM) of arginine was added. These results indicate that arginase II prevents NO-dependent apoptosis of RAW 264.7 cells by depleting intracellular arginine and by decreasing NO production.
Human Bubr1 Is a Mitotic Checkpoint Kinase That Monitors Cenp-E Functions at Kinetochores and Binds the Cyclosome/APC
Authors: Chan G.K.T. , Jablonski S.A. , Sudakin V. , Hittle J.C. , Yen T.J.
Published: July 2002

Human cells express two kinases that are related to the yeast mitotic checkpoint kinase BUB1. hBUB1 and hBUBR1 bind to kinetochores where they are postulated to be components of the mitotic checkpoint that monitors kinetochore activities to determine if chromosomes have achieved alignment at the spindle equator (Jablonski, S.A., G.K.T. Chan, C.A. Cooke, W.C. Earnshaw, and T.J. Yen. 1998. Chromosoma. 107:386–396). In support of this, hBUB1 and the homologous mouse BUB1 have been shown to be important for the mitotic checkpoint (Cahill, D.P., C. Lengauer, J. Yu, G.J. Riggins, J.K. Willson, S.D. Markowitz, K.W. Kinzler, and B. Vogelstein. 1998. Nature. 392:300–303; Taylor, S.S., and F. McKeon. 1997. Cell. 89:727–735). We now demonstrate that hBUBR1 is also an essential component of the mitotic checkpoint. hBUBR1 is required by cells that are exposed to microtubule inhibitors to arrest in mitosis. Additionally, hBUBR1 is essential for normal mitotic progression as it prevents cells from prematurely entering anaphase. We establish that one of hBUBR1's checkpoint functions is to monitor kinetochore activities that depend on the kinetochore motor CENP-E. hBUBR1 is expressed throughout the cell cycle, but its kinase activity is detected after cells have entered mitosis. hBUBR1 kinase activity was rapidly stimulated when the spindle was disrupted in mitotic cells. Finally, hBUBR1 was associated with the cyclosome/anaphase-promoting complex (APC) in mitotically arrested cells but not in interphase cells. The combined data indicate that hBUBR1 can potentially provide two checkpoint functions by monitoring CENP-E–dependent activities at the kinetochore and regulating cyclosome/APC activity.
Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy
Authors: Sullivan Teresa , Escalante-Alcalde Diana , Bhatt Harshida , Anver Miriam , Bhat Narayan , Nagashima Kunio , Stewart Colin L. , Burke Brian
Published: July 2002

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.
Downregulation of 14-3-3σ Prevents Clonal Evolution and Leads to Immortalization of Primary Human Keratinocytes
Authors: Dellambra Elena , Golisano Osvaldo , Bondanza Sergio , Siviero Emanuela , Lacal Pedro , Molinari Marta , D'Atri Stefania , De Luca Michele
Published: July 2002

In human epidermal keratinocytes, replicative senescence, is determined by a progressive decline of clonogenic and dividing cells. Its timing is controlled by clonal evolution, that is, by the continuous transition from stem cells to transient amplifying cells. We now report that downregulation of 14-3-3σ, which is specifically expressed in human stratified epithelia, prevents keratinocyte clonal evolution, thereby forcing keratinocytes into the stem cell compartment. This allows primary human keratinocytes to readily escape replicative senescence. 14-3-3σ–dependent bypass of senescence is accompanied by maintenance of telomerase activity and by downregulation of the p16INK4a tumor suppressor gene, hallmarks of keratinocyte immortalization. Taken together, these data therefore suggest that inhibition of a single endogenous gene product fosters immortalization of primary human epithelial cells without the need of exogenous oncogenes and/or oncoviruses.
An Essential Role for a Membrane Lipid in Cytokinesis
Authors: Emoto Kazuo , Umeda Masato
Published: July 2002

Phosphatidylethanolamine (PE) is a major membrane phospholipid that is mainly localized in the inner leaflet of the plasma membrane. We previously demonstrated that PE was exposed on the cell surface of the cleavage furrow during cytokinesis. Immobilization of cell surface PE by a PE-binding peptide inhibited disassembly of the contractile ring components, including myosin II and radixin, resulting in formation of a long cytoplasmic bridge between the daughter cells. This blockade of contractile ring disassembly was reversed by removal of the surface-bound peptide, suggesting that the PE exposure plays a crucial role in cytokinesis. To further examine the role of PE in cytokinesis, we established a mutant cell line with a specific decrease in the cellular PE level. On the culture condition in which the cell surface PE level was significantly reduced, the mutant ceased cell growth in cytokinesis, and the contractile ring remained in the cleavage furrow. Addition of PE or ethanolamine, a precursor of PE synthesis, restored the cell surface PE on the cleavage furrow and normal cytokinesis. These findings provide the first evidence that PE is required for completion of cytokinesis in mammalian cells, and suggest that redistribution of PE on the cleavage furrow may contribute to regulation of contractile ring disassembly.
CENP-meta, an Essential Kinetochore Kinesin Required for the Maintenance of Metaphase Chromosome Alignment in Drosophila
Authors: Yucel Jennifer K. , Marszalek Janet D. , McIntosh J. Richard , Goldstein Lawrence S.B. , Cleveland Don W. , Philp Alastair Valentine
Published: July 2002

CENP-meta has been identified as an essential, kinesin-like motor protein in Drosophila. The 257-kD CENP-meta protein is most similar to the vertebrate kinetochore-associated kinesin-like protein CENP-E, and like CENP-E, is shown to be a component of centromeric/kinetochore regions of Drosophila chromosomes. However, unlike CENP-E, which leaves the centromere/kinetochore region at the end of anaphase A, the CENP-meta protein remains associated with the centromeric/kinetochore region of the chromosome during all stages of the Drosophila cell cycle. P-element–mediated disruption of the CENP-meta gene leads to late larval/pupal stage lethality with incomplete chromosome alignment at metaphase. Complete removal of CENP-meta from the female germline leads to lethality in early embryos resulting from defects in metaphase chromosome alignment. Real-time imaging of these mutants with GFP-labeled chromosomes demonstrates that CENP-meta is required for the maintenance of chromosomes at the metaphase plate, demonstrating that the functions required to establish and maintain chromosome congression have distinguishable requirements.