bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmoviruses: nonviral/viral vectors for gene therapy.
Authors: Noguiez-Hellin P , Meur M R , Salzmann J L , Klatzmann D
Published: July 2002

We have generated a chimeric gene transfer vector that combines the simplicity of plasmids with the infectivity and long-term expression of retroviruses. We replaced the env gene of a Moloney murine leukemia virus-derived provirus by a foreign gene, generating a plasmid that upon transfer to tumor cells generates noninfectious retroviral particles carrying the transgene. We added to this plasmid an independent expression cassette comprising a cytomegalovirus promoter, an amphotropic retroviral envelope, and a polyadenylylation signal from simian virus 40. These constructs were designed to minimize the risk of recombination generating replication-competent retroviruses. Their only region of homology is a 157-bp sequence with 53% identity. We show that the sole transfection of this plasmid in various cell lines generates infectious but defective retroviral particles capable of efficiently infecting and expressing the transgene. The formation of infectious particles allows the transgene propagation in vitro. Eight days after transfection in vitro, the proportion of cells expressing the transgene is increased by 10-60 times. There was no evidence of replication-competent retrovirus generation in these experiments. The intratumoral injection of this plasmid, but not of the control vector lacking the env gene, led to foci of transgene-expressing cells, suggesting that the transgene had propagated in situ. Altogether, these "plasmoviruses" combine advantages of viral and non-viral vectors. They should be easy to produce in large quantity as clinical grade materials and should allow efficient and safe in situ targeting of tumor cells.
Safety in numbers: Sophisticated vigilance by Allenby’s gerbil
Authors: Rosenzweig Michael L. , Abramsky Zvika , Subach Aziz
Published: July 2002

Since 1963, nonlinear predation theory has predicted that, at low population densities, victim species may well be mutualistic rather than competitive. Theory identifies this mutualism as a principal source of dynamic instability in the interaction. Using gerbils and trained barn owls, we conducted the first (to our knowledge) field tests of the theory’s prediction of mutualism. The behavior of the gerbils confirms its existence.
Topology of allosteric regulation of lactose permease
Authors: Seok Yeong-Jae , Sun Jianzhong , Kaback H. Ronald , Peterkofsky Alan
Published: July 2002

Sugar transport by some permeases in
Escherichia coli
is allosterically regulated by the phosphorylation state of the intracellular regulatory protein, enzyme IIA
glc
of the phospho
enol
pyruvate:sugar phosphotransferase system. A sensitive radiochemical assay for the interaction of enzyme IIA
glc
with membrane-associated lactose permease was used to characterize the binding reaction. The binding is stimulated by transportable substrates such as lactose, melibiose, and raffinose, but not by sugars that are not transported (maltose and sucrose). Treatment of lactose permease with
N
-ethylmaleimide, which blocks ligand binding and transport by alkylating Cys-148, also blocks enzyme IIA
glc
binding. Preincubation with the substrate analog β-
d
-galactopyranosyl 1-thio-β-
d
-galactopyranoside protects both lactose transport and enzyme IIA
glc
binding against inhibition by
N
-ethylmaleimide. A collection of lactose permease replacement mutants at Cys-148 showed, with the exception of C148V, a good correlation of relative transport activity and enzyme IIA
glc
binding. The nature of the interaction of enzyme IIA
glc
with the cytoplasmic face of lactose permease was explored. The N- and C-termini, as well as five hydrophilic loops in the permease, are exposed on the cytoplasmic surface of the membrane and it has been proposed that the central cytoplasmic loop of lactose permease is the major determinant for interaction with enzyme IIA
glc
. Lactose permease mutants with polyhistidine insertions in cytoplasmic loops IV/V and VI/VII and periplasmic loop VII/VIII retain transport activity and therefore substrate binding, but do not bind enzyme IIA
glc
, indicating that these regions of lactose permease may be involved in recognition of enzyme IIA
glc
. Taken together, these results suggest that interaction of lactose permease with substrate promotes a conformational change that brings several cytoplasmic loops into an arrangement optimal for interaction with the regulatory protein, enzyme IIA
glc
. A topological map of the proposed interaction is presented.
Overexpression of a truncated human topoisomerase III partially corrects multiple aspects of the ataxia-telangiectasia phenotype
Authors: Fritz Eberhard , Elsea Sarah H. , Patel Pragna I. , Meyn M. Stephen
Published: July 2002

Ataxia-telangiectasia (A-T) is a recessive human disease characterized by radiation sensitivity, genetic instability, immunodeficiency, and high cancer risk. We previously used expression cloning to identify CAT4.5, a human cDNA that partially suppresses multiple aspects of the A-T phenotype upon transfection into cultured cells. Sequencing CAT4.5 revealed a 1.1-kb intronic fragment followed by a related ORF of 2.5 kb that encodes the near full-length ORF for
hTOP3
, the first mammalian topoisomerase III to be identified. Endogenous expression of
hTOP3
was found in all human tissues tested. Both pCAT4.5 and an antisense
hTOP3
construct were able to inhibit spontaneous and radiation-induced apoptosis in A-T fibroblasts, whereas overexpression of a full-length
hTOP3
cDNA did not. We postulate that topoisomerase III may be deregulated in A-T cells and that CAT4.5 complements the A-T phenotype via a dominant-negative mechanism. Furthermore, functional correction of hyper-recombination in A-T cells by CAT4.5 supports the hypothesis that the hTOP3 topoisomerase is involved in the control of genomic stability, perhaps in concert with the Bloom or Werner syndrome DNA helicases.
Intrathymic selection of NK1.1+α/β T cell antigen receptor (TCR)+cells in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I-Ad
Authors: Iwabuchi Chikako , Iwabuchi Kazuya , Nakagawa Ken-ichi , Takayanagi Toshiaki , Nishihori Hiroki , Tone Saori , Ogasawara Kazumasa , Good Robert A. , Onoé Kazunori
Published: July 2002

Generation and negative selection of NK1.1+α/β T cell receptor (TCR)+thymocytes were analyzed using TCR-transgenic (B10.D2 × DO10)F1and (C57BL/6 × DO10)F1mice and Rag-1−/−/DO10 mice, which had been established by breeding and backcrossing between Rag-1−/−and DO10 mice. Almost all T cells from these mice were shown to bear Vα13/Vβ8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1+Vα13/Vβ8.2+thymocytes was generated in these mice. However, the actual cell number of both NK1.1+and NK1.1−thymocytes in I-Ad/dmice (positive selecting background) was larger than that in I-Ab/dmice (negative selecting background). Markedly low but significant proportions of NK1.1+Vα13/Vβ8.2+cells were detected in the spleens from I-Ad/dand I-Ab/dmice. It was shown that the splenic NK1.1+T cells of the I-Ab/dmice were anergized against stimulation through TCR. When (B10.D2 × DO10)F1and (C57BL/6 × DO10)F1mice were given cOVA, extensive or intermediate elimination of NK1.1+α/βTCR+thymocytes was induced in I-Ad/dor I-Ab/dmice, respectively. However, the clonal elimination was not as complete as that seen in the major NK1.1−thymocyte population. The present findings indicate that normal generation of NK1.1+α/βTCR+thymocytes occurs in the absence of Vα14-Jα281 and that substantial negative selection operates on the NK1.1+α/βTCR+cells.
Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor
smad2
Authors: Weinstein Michael , Yang Xiao , Li Cuiling , Xu Xiaoling , Gotay Jessica , Deng Chu-Xia
Published: July 2002

smad
genes constitute a family of nine members whose products serve as intracellular mediators of transforming growth factor β signals. SMAD2, which is a tumor suppressor involved in colorectal and lung cancer, has been shown to induce dorsal mesoderm in
Xenopus laevis
in response to transforming growth factor β and activins. The
smad2
gene is expressed ubiquitously during murine embryogenesis and in many adult mouse tissues. Animals that lacked
smad2
died before 8.5 days of development (E8.5). E6.5 homozygous mutants were smaller than controls, lacked the extraembryonic portion of the egg cylinder, and appeared strikingly similar to E6.5
smad4
mutants. This similarity was no longer evident at E7.5, however, because the
smad2
mutants contained embryonic ectoderm within their interiors. Molecular analysis showed that
smad2
mutant embryos did not undergo gastrulation or make mesoderm. The results demonstrate that
smad2
is required for egg cylinder elongation, gastrulation, and mesoderm induction.
“What” and “how”: Evidence for the dissociation of object knowledge and mechanical problem-solving skills in the human brain
Authors: Hodges John R. , Spatt Josef , Patterson Karalyn
Published: July 2002

Patients with profound semantic deterioration resulting from temporal lobe atrophy have been reported to use many real objects appropriately. Does this preserved ability reflect (
i
) a separate component of the conceptual knowledge system (“action semantics”) or (
ii
) the operation of a system that is independent of conceptual knowledge of specific objects, and rather is responsible for general mechanical problem-solving skills, triggered by object affordances? We contrast the performance of three patients—two with semantic dementia and focal temporal lobe atrophy and the third with corticobasal degeneration and biparietal atrophy—on tests of real object identification and usage, picture-based tests of functional semantic knowledge, and a task requiring selection and use of novel tools. The patient with corticobasal degeneration showed poor novel tool selection and impaired use of real objects, despite near normal semantic knowledge of the same objects’ functions. The patients with semantic dementia had the expected deficit in object identification and functional semantics, but achieved flawless and effortless performance on the novel tool task. Their attempts to use this same mechanical problem-solving ability to deduce (sometimes successfully but often incorrectly) the use of the real objects provide no support for the hypothesis of a separate action-semantic system. Although the temporal lobe system clearly is necessary to identify “what” an object is, we suggest that sensory inputs to a parietal “how” system can trigger the use of objects without reference to object-specific conceptual knowledge.
Linguistic threat activates the human amygdala
Authors: Isenberg N. , Silbersweig D. , Engelien A. , Emmerich S. , Malavade K. , Beattie B. , Leon A. C. , Stern E.
Published: July 2002

Studies in animals demonstrate a crucial role for the amygdala in emotional and social behavior, especially as related to fear and aggression. Whereas lesion and functional-imaging studies in humans indicate the amygdala’s participation in assessing the significance of nonverbal as well as paralinguistic cues, direct evidence for its role in the emotional processing of linguistic cues is lacking. In this study, we use a modified Stroop task along with a high-sensitivity neuroimaging technique to target the neural substrate engaged specifically when processing linguistic threat. Healthy volunteer subjects were instructed to name the color of words of either threat or neutral valence, presented in different color fonts, while neural activity was measured by using H
2
15
O positron-emission tomography. Bilateral amygdalar activation was significantly greater during color naming of threat words than during color naming of neutral words. Associated activations were also noted in sensory-evaluative and motor-planning areas of the brain. Thus, our results demonstrate the amygdala’s role in the processing of danger elicited by language. In addition, the results reinforce the amygdala’s role in the modulation of the perception of, and response to, emotionally salient stimuli. The current study further suggests conservation of phylogenetically older mechanisms of emotional evaluation in the context of more recently evolved linguistic function.
Modeling evolutionary landscapes: Mutational stability, topology, and superfunnels in sequence space
Authors: Bornberg-Bauer Erich , Chan Hue Sun
Published: July 2002

Random mutations under neutral or near-neutral conditions are studied by considering plausible evolutionary trajectories on “neutral nets”—i.e., collections of sequences (genotypes) interconnected via single-point mutations encoding for the same ground-state structure (phenotype). We use simple exact lattice models for the mapping between sequence and conformational spaces. Densities of states based on model intrachain interactions are determined by exhaustive conformational enumeration. We compare results from two very different interaction schemes to ascertain robustness of the conclusions. In both models, sequences in a majority of neutral nets center around a single “prototype sequence” of maximum mutational stability, tolerating the largest number of neutral mutations. General analytical considerations show that these topologies by themselves lead to higher steady-state evolutionary populations at prototype sequences. On average, native thermodynamic stability increases toward a maximum at the prototype sequence, resulting in funnel-like arrangements of native stabilities in sequence space. These observations offer a unified perspective on sequence design, native stability, and mutational stability of proteins. These principles are generalizable from native stability to any measure of fitness provided that its variation with respect to mutations is essentially smooth.
Nrf2 is essential for protection against acute pulmonary injury in mice
Authors: Chan Kaimin , Kan Yuet Wai
Published: July 2002

Nrf2 is a member of the “cap ‘n’ collar” family of transcription factors. These transcription factors bind to the NF-E2 binding sites (GCTGAGTCA) that are essential for the regulation of erythroid-specific genes. Nrf2 is expressed in a wide range of tissues, many of which are sites of expression for phase 2 detoxification genes. Nrf2
−/−
mice are viable and have a normal phenotype under normal laboratory conditions. The NF-E2 binding site is a subset of the antioxidant response elements that have the sequence GCNNNGTCA. The antioxidant response elements are regulatory sequences found on promoters of several phase 2 detoxification genes that are inducible by xenobiotics and antioxidants. We report here that Nrf2
−/−
mice are extremely susceptible to the administration of the antioxidant butylated hydroxytoluene. With doses of butylated hydroxytoluene that are tolerated by wild-type mice, the Nrf2
−/−
mice succumb from acute respiratory distress syndrome. Gene expression studies show that the expression of several detoxification enzymes is altered in the Nrf2
−/−
mice. The Nrf2
−/−
mice may prove to be a good
in vivo
model for toxicological studies. As oxidative damage causes DNA breakage, these mice may also be useful for testing carcinogenic agents.
Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis: A general mechanism to accumulate effector cells in inflammation
Authors: Dibbert Birgit , Weber Martina , Nikolaizik Wilfried H. , Vogt Peter , Schöni Martin H. , Blaser Kurt , Simon Hans-Uwe
Published: July 2002

Neutrophils are important effector cells in immunity to microorganisms, particularly bacteria. Here, we show that the process of neutrophil apoptosis is delayed in several inflammatory diseases, suggesting that this phenomenon may represent a general feature contributing to the development of neutrophilia, and, therefore, in many cases to host defense against infection. The delay of neutrophil apoptosis was associated with markedly reduced levels of Bax, a pro-apoptotic member of the Bcl-2 family. Such Bax-deficient cells were also observed upon stimulation of normal neutrophils with cytokines present at sites of neutrophilic inflammation, such as granulocyte and granulocyte–macrophage colony-stimulating factors,
in vitro
. Moreover, Bax-deficient neutrophils generated by using Bax antisense oligodeoxynucleotides demonstrated delayed apoptosis, providing direct evidence for a role of Bax as a pro-apoptotic molecule in these cells. Interestingly, the Bax gene was reexpressed in Bax-deficient neutrophils under conditions of cytokine withdrawal. Thus, both granulocyte expansion and the resolution of inflammation appear to be regulated by the expression of the Bax gene in neutrophils.
Perlecan is required to inhibit thrombosis after deep vascular injury and contributes to endothelial cell-mediated inhibition of intimal hyperplasia
Authors: Nugent Matthew A. , Nugent Helen M. , Iozzo Renato V. , Sanchack Kristian , Edelman Elazer R.
Published: July 2002

Perlecan, a heparan sulfate proteoglycan, has been suggested to be critical for regulation of vascular repair. We generated clones of endothelial cells expressing an antisense vector targeting domain III of perlecan. Transfected cells produced significantly less perlecan than parent cells and showed a reduced ability to inhibit the binding and mitogenic activity of fibroblast growth factor-2 in vascular smooth muscle cells. Endothelial cells were seeded onto three-dimensional polymeric matrices and implanted adjacent to porcine carotid arteries subjected to deep injury. Although the parent endothelial cells prevented occlusive thrombosis, perlecan-deficient cells were completely ineffective. The ability of endothelial cells to inhibit intimal hyperplasia, however, was abrogated only in part by perlecan suppression. The differential regulation by perlecan of these different aspects of vascular repair may explain why control of clinical clot formation does not lead to full control of intimal hyperplasia. Thus the use of genetically modified tissue-engineered cells provides a new approach for dissecting the role of specific factors within the complex environment of the blood vessel wall.
Direct localization of a β-subunit domain on the three-dimensional structure of
Escherichia coli
RNA polymerase
Authors: Opalka Natacha , Mooney Rachel A. , Richter Catherine , Severinov Konstantin , Landick Robert , Darst Seth A.
Published: July 2002

To identify the location of a domain of the β-subunit of
Escherichia coli
RNA polymerase (RNAP) on the three-dimensional structure, we developed a method to tag a nonessential surface of the multisubunit enzyme with a protein density easily detectable by electron microscopy and image processing. Four repeats of the IgG-binding domain of
Staphylococcus aureus
protein A were inserted at position 998 of the
E. coli
RNAP β-subunit. The mutant RNAP supported
E. coli
growth and showed no apparent functional defects
in vitro
. The structure of the mutant RNAP was determined by cryoelectron microscopy and image processing of frozen-hydrated helical crystals. Comparison of the mutant RNAP structure with the previously determined wild-type RNAP structure by Fourier difference analysis at 20-Å resolution directly revealed the location of the inserted protein domain, thereby locating the region around position 998 of the β-subunit within the RNAP three-dimensional structure and refining a model for the subunit locations within the enzyme.
Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1
Authors: Aharoni Rina , Teitelbaum Dvora , Leitner Orith , Meshorer Asher , Sela Michael , Arnon Ruth
Published: July 2002

This study addresses the issue of the effect of immunomodulating therapies in the target organ—the central nervous system (CNS)—in the case of multiple sclerosis. Copolymer 1 (Cop 1, Copaxone, glatiramer acetate), an approved drug for the treatment of multiple sclerosis, is a potent inducer of Th2 regulatory cells in both mice and humans. Highly reactive Cop 1-specific T cell lines that secrete IL-4, IL-5, IL-6, IL-10, and transforming growth factor-β in response to Cop 1 and crossreact with myelin basic protein (MBP) at the level of Th2 cytokine secretion were established from both brains and spinal cords of Cop 1-treated mice. In contrast, no reactivity to the control antigen lysozyme could be obtained in lymphocytes isolated from CNS of mice injected with lysozyme. Adoptively transferred labeled Cop 1-specific suppressor cells were found in brain sections 7 and 10 days after their injection to the periphery, whereas lysozyme-specific cells were absent in the CNS. Hence, Cop 1-induced Th2 cells cross the blood–brain barrier and accumulate in the CNS, where they can be stimulatedin situby MBP and thereby exert therapeutic effects in the diseased organ. This therapeutic effect was manifested, in brains of experimental autoimmune encephalomyelitis-induced mice, by a decrease in the inflammatory cytokine interferon-γ and by secretion of the anti-inflammatory cytokine IL-10 in response to the autoantigen MBP.
Molecular determinants of membrane potential dependence in vertebrate gap junction channels
Authors: Revilla Ana , Bennett Michael V. L. , Barrio Luis C.
Published: July 2002

The conductance,
g
j
, of many gap
junctions depends on voltage between the coupled cells (transjunctional
voltage,
V
j
) with little effect of the
absolute membrane potential (
V
m
) in the two
cells; others show combined
V
j
and
V
m
dependence. We examined the molecular
determinants of
V
m
dependence by using rat
connexin 43 expressed in paired
Xenopus
oocytes. These
junctions have, in addition to
V
j
dependence,
V
m
dependence such that equal
depolarization of both cells decreases
g
j
.
The dependence of
g
j
on
V
m
was abolished by truncation of the
C-terminal domain (CT) at residue 242 but not at 257. There are two
charged residues between 242 and 257. In full-length Cx43, mutations
neutralizing either one of these charges, Arg243Gln and Asp245Gln,
decreased and increased
V
m
dependence,
respectively, suggesting that these residues are part of the
V
m
sensor. Mutating both residues together
abolished
V
m
dependence, although there is
no net change in charge. The neutralizing mutations, together or
separately, had no effect on
V
j
dependence.
Thus, the voltage sensors must differ. However,
V
j
gating was somewhat modulated by
V
m
, and
V
m
gating
was reduced when the
V
j
gate was closed.
These data suggest that the two forms of voltage dependence are
mediated by separate but interacting domains.
Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM
Authors: Boes Marianne , Schmidt Tara , Linkemann Kathrin , Beaudette Britte C. , Marshak-Rothstein Ann , Chen Jianzhu
Published: July 2002

Individuals with systemic lupus erythematosus and rheumatoid arthritis are characterized by the presence of high levels of circulating IgM and IgG autoantibodies. Although IgG autoantibodies often are pathogenic, the role of IgM autoantibodies in autoimmune disease is not clear. Using mice that are unable to secrete IgM but are able to express surface IgM and IgD and to secrete other classes of immunoglobulins, we examined the effect of the absence of secreted IgM in the development of IgG autoantibodies and autoimmune disease in lupus-prone lymphoproliferative (lpr) mice. Compared with regular lpr mice, lpr mice that lack secreted IgM developed elevated levels of IgG autoantibodies to double-stranded DNA and histones and had more abundant deposits of immune complexes in the glomeruli; they also suffered more severe glomerulonephritis and succumbed to the disease at an earlier age. Similarly, the absence of secreted IgM also resulted in an accelerated development of IgG autoantibodies in normal mice. These findings suggest that secreted IgM, including IgM autoantibodies produced naturally or as part of an autoimmune response, may lessen the severity of autoimmune pathology associated with IgG autoantibodies.
Selective Interference During the Retrieval of Spatial and Verbal Information from Episodic Long‐term Memory
Authors: Heil Martin , Rösler Frank , Rauch Melina , Hennighausen Erwin
Published: July 2002

Recent studies have shown that the retrieval of spatial versus verbal information is dissociated by the topography of cortical activation despite the fact that response times did not differ. We investigated whether the topographical dissociation will become apparent in a behavioural dissociation if subjects repeatedly have to switch between the retrieval task and one of two tasks which differ in the amount of load they put on the respective representational system. Therefore, retrieval of both spatial and verbal information was combined with no switching task, a mental rotation task, and a gender classification task. In the no‐switching condition response times were identical for spatial and verbal information. In contrast, a more pronounced difficulty effect for spatial information was observed with mental rotation as the switching task, whereas the reverse pattern was found with gender classification. The results support the assumption of localized neural networks specialized for distinct aspects of information processing.
Comparing Short‐term Memory and Memory for Rapidly Presented Visual Stimuli
Authors: Coltheart Veronika
Published: July 2002

What similarities and differences are there between memory for short lists shown at one item per second and memory for such lists after rapid serial visual presentation (RSVP) at much higher rates—eight items per second? This paper reports that, when pictures are shown at eight per second or one per second, phonological similarity of the picture names reduces recall at the one item per second rate, but not at the eight item per second rate. In contrast, when subjects are shown the written names of the pictures, phonological similarity reduces recall at both rates. It is concluded that phonological coding does not occur for picture lists shown at high rates. The mechanisms underlying memory for pictures and words shown at RSVP and short‐term memory rates are considered.
Localizing Localization: The Role of Working Memory in Auditory Localization
Authors: Merat Natasha , Groeger John A. , Withington Deborah J.
Published: July 2002

It is unclear from current accounts of working memory which, if any, of its components might be involved in our ability to specify the location of a sound source. A series of studies were performed to assess the degree of interference in localization of broadband noise, by a concurrent articulatory suppression (articulatory loop—Experiment 1), serial recall (phonological store and articulatory loop—Experiment 2), and Paced Visual Serial Addition Test (central executive—Experiment 3). No significant disruption of auditory localization was revealed by the first two experiments, ruling out a role for the phonological loop in auditory localization. In Experiment 3, a large degree of error was exhibited in localization, when performed concurrently with the addition task, indicating a requirement for central resources. This suggestion is confirmed by comparison of localization performance across all three studies, which demonstrates a clear deterioration in performance as the demand of concurrent tasks on central resources increases. Finally, concurrent localization was shown to disrupt the primacy portion of the serial position curve, as well as performance on the Paced Visual Serial Addition Test.
Self‐concept Differentiation and Depressive Symptomatology in Children
Authors: Heath Nancy Lee , Brown Andrea E.
Published: July 2002

Self‐concept differentiation is the degree to which separate domains of the self‐concept are differentiated from one another. Two studies of children's self‐reported depressive symptomatology and self‐concept differentiation were completed. Study 1 found higher levels of self‐concept differentiation associated with greater depressive symptomatology. Study 2 replicated this finding but further revealed a trend for elevated self‐concept differentiation to be related to a positive outcome at 5‐week follow‐up in the depressed sample.
Meeting the Challenge of Distressed Urban Areas
Authors: Conway Maureen , Konvitz Josef
Published: July 2002

The emergence of distressed urban areas in the 1990s was unexpected. Governments have reacted with a series of policy initiatives which have increasingly focused on area-based strategies, partnerships and the formulation of a metropolitan vision. The scale of the problem-up to 20 per cent of the total population may live in distressed urban areas—and the complexity of causes are two factors which have complicated the design and implementation of policy. Better indicators are needed, especially to check the tendency towards a rhetoric of polarisation which makes the problems appear impossible to solve. A recent OECD study and a study of partnerships undertaken by the European Foundation for the Improvement of Living and Working Conditions (EFILWC) call attention to the importance of local participation and of business and labour in local strategies for regeneration. To compare experiences and analyses their policy implications, the OECD and the EFILWC organised a conference in Dublin in 1998, of which this paper is an analytical report. One of the findings of the conference deserving further study concerns the role of the media in shaping public opinion on regeneration issues; another concerns the need for preventive strategies and policies; and a third concerns the linkages between regeneration, education and job training and employment. There is a need for policy-makers and academic researchers to work towards a common agenda and a shared discourse. In the final analysis, the study of distressed areas can reveal much about the nature of larger urban economic and social processes. But the responsibility of government to act means making some informed judgement about how to intervene, and why intervention is necessary, even on the basis of imperfect information.
Bridging Urban Digital Divides? Urban Polarisation and Information and Communications Technologies (ICTs)
Authors: Graham Stephen
Published: July 2002

The societal diffusion of information and communications technologies (ICTs) remains starkly uneven at all scales. It is in the contemporary city that this unevenness becomes most visible. In cities, clusters and enclaves of 'superconnected' people, firms and institutions often rest cheek-by-jowel with large numbers of people with non-existent or rudimentary access to communications technologies. In such a context, this paper has two objectives, reflected in its two parts. The first part of the paper seeks to demonstrate that dominant trends in ICT development are currently helping to support new extremes of social and geographical unevenness within and between human settlements and cities, in both the North and the South. The paper's second part aims to explore the prospect that such stark 'urban digital divides' might be ameliorated through progressive and innovative policy initiatives which treat cities and electronic technologies in parallel. It does this using a range of illustrative exemplars from a variety of contexts.
Are there Ethnic Enclaves/Ghettos in English Cities?
Authors: Johnston Ron , Forrest James , Poulsen Michael
Published: July 2002

The residential segregation of ethnic groups in urban areas remains an issue of importance for policy-making in multicultural societies, such as England's, with levels of segregation frequently linked to questions of social exclusion and equal treatment. But how segregated are ethnic groups in England? Most studies answer this question using single indices which address one aspect only of a multidimensional concept. In this paper, an alternative approach is used which identifies residential area types according to the degree of ethnic mixing; we evaluate their relative importance in 18 English cities in the light of Boal and Peach's arguments regarding the processes and patterns involved in segregation. We find little evidence of significant segregation of Black ethnic groups, but more with regard to Asian groups-especially outside London.
Recent Changes in the Social Rented Sector in The Netherlands
Authors: Priemus Hugo
Published: July 2002

The Netherlands has a large and differentiated stock of social rented dwellings, forming more than 40 per cent of the total housing stock. Housing associations are by far the largest providers of housing services in this sector. Traditionally, these associations were subsidised heavily but since 1995 Dutch government has no longer directly subsidised these associations. This paper deals with changes in Dutch housing associations in a period (1988-95) characterised by government austerity, deregulation, market conformity, privatisation and promotion of home-ownership. It is explained how the housing associations were able to survive and even maintain prospects for a promising future in a political climate that threatened the social rented sector. It is clear that housing associations can now operate more independently than in the past. This is seen as a positive development, but the government is now discovering the drawbacks of complete privatisation. A firmer embedding in a public framework is considered desirable now. Recently the cabinet introduced a strengthening of public supervision. The housing associations' umbrella organisations presented their own National Housing Programme and published a business code for housing associations. A crucial issue has not been discussed so far: who will subsidise the housing investments for low-income households in periods of economic stagnation?
Ethnic Minority Unemployment and Spatial Mismatch: The Case of London
Authors: Fieldhouse Edward A.
Published: July 2002

Unemployment amongst Britain's ethnic minorities is approximately twice that of the white population. Spatial mismatch theory suggests that the concentration of the ethnic minority population in declining inner-city areas may be partially responsible for part of this disparity. Alternative explanations include different population characteristics and racial discrimination. This paper uses data from the 1991 Census to explore the geography of minority ethnic unemployment in Greater London and attempts to evaluate the importance of the geographical distribution of ethnic minorities (and other factors) in understanding unemployment differences. It is argued that spatial mismatch provides an unsatisfactory explanation of Asian unemployment in London and, at best, a partial explanation of black unemployment. Rather, there is a complex interrelationship between unemployment, ethnicity and spatial location which is mediated by the local context.
The Turks in Bulgaria: Post-1989 Developments*
Authors: Eminov Ali
Published: July 2002

This article explores the status of Turks in Bulgaria under the transition from Communism to post-Communism. After a summary of the demography of the Turkish population in Bulgaria, the paper focuses on developments in three specific areas: religious, political, and educational issues. For each issue a brief historical background is given but the emphasis is on developments since 1989. Since the article is an expanded version of a presentation on East European Linguistic Minorities, the issue of Turkish language and Turkish language education in Bulgaria is discussed in greater detail than religious and political issues. This in no way implies that the latter are any less important.
Transforming Work Experience in Higher Education
Authors: Blackwell Alison , Bowes Lindsey , Harvey Lee , Hesketh Anthony J. , Knight Peter T.
Published: July 2002

Abstract It has frequently been claimed that work experience can contribute to higher educational standards in schools and in higher education and contribute to the development of a flexible, highly‐skilled and enterprising labour force. This potential was endorsed by the Dearing Report on higher education, although there is little research evidence about the contribution of work experience to the higher education curriculum. This article reports on four empirical studies of work experience in higher education, which suggest that work experience is related to a more positive view of the learning experience and to higher employment rates. However, retrospective views of graduates tend to be more positive than those of current undergraduates and there appear to be distinct subject variations in the impact of different types of work experience. It is argued that the potential is more likely to be realised where work experience placements have six characteristics of good practice and where the higher education curriculum consistently encourages students to reflect well on their own learning.
Are close relationships in adolescence linked with partner relationships in midlife? A longitudinal, prospective study
Authors: Möller Kristiina , Stattin Håkan
Published: July 2002

Utilising data from a Swedish longitudinal project, relationships with parents and friends were studied at ages 13 through 18, and with partners at age 37. The participants (N = 131, 56 females, 75 males) were either married or cohabiting in long-term relationships in midlife. In support of previous studies, which rely mostly on retrospective ” ndings, we found in this longitudinal study that adolescents with affectionate and trustful relationships with their parents reported greater satisfaction with their partner relationships in midlife. This was specifically true for father-son relationships. Parent-parent relations in adolescence were not linked with the quality of adult partner relationships. Boys who were shy in relation to friends were more dissatisfied with their partner relationships, and boys who regarded cross-gender relationships as less important in adolescence were more satis” ed with their adult partner relationships. Girls who were more worried about cross-gender relationships in adolescence were less satis” ed with their partners. On the whole, adolescent boys’ relationships with fathers had the clearest link with later adult partner relationships.
Ovarian Toxicity of 4-Vinylcyclohexene Diepoxide: A Mechanistic Model
Authors: Hoyer Patricia B. , Devine Patrick J. , Xiaoming Hu  , Thompson Kary E. , Sipes I. Glenn
Published: July 2002

Female mammals are born with a fi nite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, is associated with early menopause. Thus, the potential risks posed by ovotoxic chemicals is of concern. Our studies have focused on the environmental chemical 4-vinylcyclohexene (VCH), which is produced during the manufacture of rubber tires, flame retardants, insecticides, plasticizers, and antioxidants. Dosing of female rats and mice with the ovotoxic diepoxide metabolite of VCH, 4-vinylcyclohexene diepoxide (VCD), for 30 days destroyed the majority of ovarian primordial follicles. Using VCD in rats as a generalized model for ovotoxicity, we determined that 1) repeated daily dosing is required, 2) cell death is via apoptosis, and 3) altered expression of specific genes is involved. An integrated approach at the morphologic, biochemical, and molecular level was used to support these conclusions. Studies in isolated rat small preantral follicles (targeted for VCD-induced ovotoxicity) focused on the role of cell death genes, mitochondrion-associated events, and VCD metabolism. We also evaluated how this information relates to human risk for early menopause. These animal research results provide a better understanding of the potential risk of human exposure to environmental ovarian toxicants and greater insight as to the impact of these toxicants on reproductive health in women.
Cancer Prevention Studies in p53-Deficient Mice
Authors: Hursting Stephen D. , Perkins Susan N. , Donehower Lawrence A. , Davis Barbara J.
Published: July 2002

Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice defi cient in 1 (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. We observed in p53-/- mice that calorie restriction (CR) increased the latency of spontaneous tumor development (mostly lymphomas) by approximately 75%, decreased serum insulin-like growth factor-1 (IGF-1) and leptin levels, slowed thymocyte cell cycle traverse, and induced apoptosis in immature thymocytes. In p53+/- mice, CR and a 1 d/wk fast each delayed spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreased serum IGF-1 and leptin levels, even when begun late in life. In p53+/- Wnt-1 transgenic mice, a mammary tumor model, the same interventions increased mammary tumor latency and reduced mean serum IGF-1 and leptin levels to <50 % of those of control mice. We capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine—induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches. These examples clearly indicate that mice with specific (and humanlike) genetic susceptibilities for cancer are powerful models for testing interventions that may inhibit carcinogenesis in humans.
Immunohistochemical and Ultrastructural Studies of 2,6-Dimethylaniline-induced Nasal Proliferative Lesions in a Rat Two-stage Nasal Carcinogenesis Model Initiated with N-bis(2-hydroxypropyl)nitrosamine
Authors: Koujitani Takatoshi , Yasuhara Kazuo , Toyosawa Kaoru , Shimada Akinori , Onodera Hiroshi , Takagi Hisayoshi , Tamura Toru , Hirose Masao , Mitsumori Kunitoshi
Published: July 2002

Proliferative lesions induced by 2,6-dimethylaniline (DMA) in a two-stage rat nasal carcinogenesis model were immunohistochemically and ultrastructurally investigated. Male F344 rats received diet containing 3,000 ppm DMA for 52 weeks after initiation with a single subcutaneous injection of 2400 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN). Histopathologically, proliferation of Bowman's glands, glandular hyperplasias, dysplastic foci, adenomas, and carcinomas were observed in treated rats. These nasal lesions mostly arose in the olfactory mucosa of the nasal cavity. Immunohistochemically, they were positive for cytokeratin and/or collagen type IV antibodies. Ultrastructurally, intracytoplasmic dense secretory granules (200—850 nm in diameter), identical to those in normal Bowman's glands, were observed in all the lesions, providing further support from an origin from these glands. Based on their cellular characterization, growth pattern and/or proliferative activity, two morphological continua were evident, one from dysplastic foci to carcinomas and the other from proliferation of Bowman's glands to glandular hyperplasias and adenomas. These results suggest that dysplastic foci arise from Bowman's glands and progress to carcinomas, while proliferation of Bowman's glands result in glandular hyperplasias and adenomas.
Induction of Pancreatic Islet Cell Tumors in Rats by Repeated Intravenous Administration of 4-hydroxyaminoquinoline 1-oxide
Authors: Imazawa Takayoshi , Nishikawa Akiyoshi , Shibutani Makoto , Ogasawara Hiroyuki , Furukawa Fumio , Ikeda Takako , Suda Koichi , Hirose Masao
Published: July 2002

The inducibility of pancreatic islet cell tumors by administration of 4-hydroxyaminoquinolin e 1-oxide (4HAQO) was investigated in male 6-week-old Sprague—Dawley rats. Rats were given 4HAQO intravenously at a weekly dose of 5 mg/kg 4 times (group 1) or a single dose of 10 mg/kg (group 2). Control rats received the vehicle alone (group 3). Fifty-six weeks after the first 4HAQO administration, all surviving animals were killed and the pancreas was examined histopathologically, immunohistochemically and ultrastructurally. The incidences and multiplicities of islet cell tumors in groups 1, 2, and 3 were 52.3% ( p < 0.05 vs group 2, p < 0.01 vs group 3), 19.2% and 0%, and 0.70/animal ( p < 0.05 vs group 2, p < 0.01 vs group 3), 0.23 and 0, respectively. Islet cell carcinomas were induced only in group 1, accounting for 6/44 (26%) tumors. Islet cell hyperplasias were found in 61.4% ( p < 0.05 vs group 3), 42.3% and 10.0% of groups 1, 2, and 3, with multiplicities of 0.95 ( p < 0.05 vs groups 2 and 3), 0.54 and 0.20, respectively. As compared with normal islets from control subjects, islet cell tumors showed an increase in the number of insulin positive cells associated with cytological features indicative of enhanced insulin synthesis and secretion, and a decrease in the number of glucagon positive cells without ultrastructural signs of modified secretory activity. Thus our results indicate that repeated intravenous administration of 4HAQO to rats is useful for the induction of islet cell tumors at high incidence.
Suppressive Effects on Allergic Contact Dermatitis by Short-Term Fasting
Authors: Nakamura Harunobu , Kouda Katsuyasu , Wenying Fan  , Watanabe Tomoyuki , Takeuchi Hiroichi
Published: July 2002

Fasting alters various hormonal and immune conditions. It has been reported that delayed type immune response to the injection of keyhole limpet hemocyanin was depressed by short-term fasting. In this study, we adopted the computer-assisted image analyzer for histopathological analysis and evaluated the infl uence of short-term fasting on allergic contact dermatitis induced by 2,4-dinitrofluorobenzene (DNFB). Mice were sensitized by painting of DNFB to the abdomen. After the sensitization, mice were challenged by DNFB painting to the ear. Fasting started 24 hour before (48-hour fasted group) or immediately after (24-hour fasted group) the challenging. Fasting without DNFB treatment did not induce remarkable change of ear thickness, ear tissue, serum albumin, serum total protein, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, or serum creatine phosphokinase. In contrast, fasting suppressed the increment of ear thickness in the DNFB-treated group in this study. We could also demonstrate, using the computerized image analyzer, that both lymphocyte infi ltration and the edema in the dermis were suppressed in fasted mice treated with DNFB. Further, edema in the dermis was inhibited more strongly in 48-hour fasted mice than in 24-hour fasted mice. These fi ndings indicate that short-term fasting induce histopathological changes in the state of contact dermatitis.
Specific Genomic Alterations in Rat Renal Cell Carcinomas Induced by N-Ethyl-N-hydroxyethylnitrosamine
Authors: Konishi Noboru , Nakamura Mitsutoshi , Ishida Eiwa , Kawada Yoichi , Nishimine Masayoshi , Nagai Hisaki , Emi Mitsuru
Published: July 2002

To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifi cations and deletions. Comparison of DNAs from tumor against those from corresponding nontumorous kidney and /or EHEN-treated kidney without development of renal tumors yielded specific alterations in terms of both amplifi ed and reduced DNA spots. Two amplifi ed spots were detected only in renal cell tumors and an additional four spots were frequent in EHEN-treated kidneys. One reduced spot was common to all tumor samples, and another was frequently detected in the tumors analyzed but not in EHEN-treated kidneys. A subset of the altered spots thus appeared to be specific for EHEN-induced renal tumorigenesis.