bluuebunny/crossref_metadata_2025 huggingface dataset:
South Asian and Caribbean Ethnic Minority Housing Choice in Britain
Authors: Peach Ceri
Published: July 2002

The paper deals with choice and constraint in ethnic minority housing in Britain. It argues that the interpretation of patterns has changed from one in which minorities were viewed as powerless victims of racist discriminatory constraint, to one in which they are seen as exercising a greater degree of autonomy. Indian and Pakistani housing tenure is shown to have great similarities in terms of owner-occupation but to diverge greatly in terms of house type and location. Bangladeshis and Caribbeans are shown to share similarities in terms of socioeconomic class and housing tenure patterns, but to differ strongly in terms of the reasons for their high concentrations in council housing and also in the locations in which they live and their trends in terms of segregation. Bangladeshis and Pakistanis are shown to have similar socioeconomic profiles, but to differ in tenure and house types. Indians, Pakistanis and Bangladeshis are shown to have similar family structures but to differ in house types. The housing patterns of Indians, Pakistanis, Bangladeshis and Caribbeans in Britain owe more to ethnicity and culture than to race.
Promoting Urban Sustainability: The Case for a Tradable Supplementary Licence System for Vehicle Use
Authors: Goddard Haynes C.
Published: July 2002

Many large cities in the world have serious regional air-quality problems, largely the product of vehicular emissions, and one manifestation of the argued insustain ability of current urban growth patterns. These problems are frequently blamed on unrestricted use of private vehicles. This paper applies the concept of sustainability to urban areas by formulating an explicit ecological constraint on airshed capacity in a region within a model of cost-effective emissions control. Solution of the model suggests that restrictions on vehicle use should play a role in achieving regional air-quality targets cost-effectively. A tradable vehicle-use permit system is described for implementing the sustainability constraint, and its relationship to other demand management proposals for constraining vehicle use is discussed, as well as the implications for the form and vitality of urban areas. This control policy would have substantially favourable impacts on air quality, vehicle congestion and uncontrolled suburban development and, given the general political unacceptability of environmental taxes, could form part of a workable and politically palatable set of policies to control greenhouse-gas emissions from the transport sector. The proposed vehicle-use permits mechanism represents a natural extension of current discussions for globally tradable carbon emission permits, and could be a principal method by which such national carbon emissions budgets might be allocated regionally.
Attachment and play in child care centres: Reliability and validity of the attachment Q-sort for mothers and professional caregivers in Italy
Authors: Cassibba Rosalinda , Van Ijzendoorn Marinus H. , D’Odorico Laura
Published: July 2002

The purpose of this article was to adapt and validate the Attachment Q-Sort (AQS; Vaughn & Waters, 1990) in the Italian context of child rearing at home and in centre care, and to analyse the associations of attachment to the mother and to the professional caregiver with play behaviour of the child. The article reports on three studies. The first study describes the procedure used to create the Italian version of the Attachment Q-Sort. Fifteen Italian experts provided the AQS descriptions of the prototypical “most secure child”; moreover, 18 Italian caregivers used the AQS to describe the hypothetical “ideal child” in the context of the child care centre. The profiles of the Italian experts were very similar to those of American experts. Italian experts and Italian caregivers also strongly agreed in their descriptions, respectively, of the “most secure” and the “ideal” child. The second study reports on the reliability of the AQS data. Eighty-six children (43% male; 59%first-borns) and their mothers and caregivers participated in the research. Children’s ages ranged from 14 to 36 months ( M = 26.6; SD = 6.78). All children spent at least 30 hours per week in the child care centres. Test-retest reliability and inter-observer agreement appeared to be satisfactory. Agreement between mother/caregiver- and observer-reported security scores was less convincing. In the third study, the associations between the network of attachment and level of play were examined. Fifty children (58% male; 60% first-borns) participated. Children’s ages ranged from 14 to 36 months ( M = 25.8; SD = 6.56). Play behaviour was observed at the child care centre during free play sessions of 30 minutes and social and cognitive play categories were coded. Secure attachment led to higher cognitive levels of play. Attachment to the caregiver was generally more influential than attachment to the mother.
Institutional Care and Developmental Outcomes of 6- and 7-year-old Children: A Contextualist Perspective
Authors: Sloutsky Vladimir M.
Published: July 2002

This paper examines effects of institutional settings on cognitive, affective, and personal development of children. Two samples consisting of 52 children, living in orphanages, and 45 kindergarten students, living with their families, were selected in Moscow, Russia; children’s ages were between 70 and 88 months. The children in both samples were compared with respect to their Wechsler scores, empathy, and level of conformity. It was found that the kindergarten children had higher Wechsler scores, a higher level of empathy, and a lower level of conformity. It was also found that the age of placement in an institution and the amount of time the child spent there were associated with Wechsler IQ score and studied measures of affective and personal development. The proposed interpretation of the detrimental institutional effects suggests that the institutions differ from the family in both the organisation of their context and in the roles of their participants. Institutional organisation is considered as a set of factors affecting the behaviours of the participants (both the children and the staff), and the process of the children’s development.
Resilience: A Dynamic Perspective
Authors: Freitas Antonio L. , Downey Geraldine
Published: July 2002

Identifying characteristics that distinguish youth who achieve adaptive outcomes in the face of adversity from those who do not has furthered our understanding of developmental psychopathology. However, accumulating evidence indicates that particular characteristics rarely serve exclusively risk or protective functions, that individuals who seem resilient on one index often do not seem so on other indices, and that individuals often are not equally resilient across contexts. These findings call for a dynamic conceptualisation of resiliency that can account for why the ways children cope with stressors vary across domain, development, and context. We organise resiliency research into a framework based on a recently proposed dynamic conceptualisation of personality (Mischel & Shoda, 1995). This framework assumes that understanding why some children show resilience in the face of adversity whereas others show difficulties requires identifying: (a) the content of and relational structure among relevant psychological mediators such as competencies, expectancies, values, and goals; and (b) the relation between these psychological mediators and relevant features of the environment. To illustrate the potential of this approach to further our understanding of resiliency, we examine and reconsider the link between IQ and conduct problems.
Assessment of Hormonally Active Agents in the Reproductive Tract of Female Nonhuman Primates
Authors: Cline J. Mark , Söderqvist Gunnar , Register Thomas C. , Williams J. Koudy , Adams Michael R. , Von Schoultz Bo
Published: July 2002

Using the ovariectomized macaque model of postmenopausal women's health, we investigated the effects of long-term treatments (5 weeks—3 years) with estradiol, conjugated equine estrogens (CEE), esterified estrogens, progestins such as medroxyprogesterone acetate (MPA) and nomegestrol acetate, CEE + MPA, tamoxifen, soybean phytoestrogens (SPEs), a variety of putative selective estrogen receptor modulators (SERMs), and androgens. Agents tested were selected on the basis of beneficial effects on arteries and/ or bone. Doses were scaled on a caloric or serum-concentration basis to approximate human clinical doses. We evaluated endometrial and mammary gland histopathology and morphometry and used immunohistochemistry to evaluate cell proliferation and expression of estrogen receptor alpha and progesterone receptor (PR). Both estradiol and CEE induced endometrial hyperplasia. MPA antagonized epithelial proliferation induced by CEE in endometrium and induced pseudodecidual stromal hyperplasia in some animals. Tamoxifen induced endometrial polyps, cystic hyperplasia, stromal fi brosis, and PR expression but not Ki-67 expression. SPEs were not estrogenic at dietary doses and antagonized estrogen-induced proliferation in the endometrium and breast. Nandrolone induced mucometra and an adenomyosis-like change. The potential SERM 17 alpha dihydroequilenin did not have uterotrophic or mammotrophic effects. In general, experimental findings in macaques have been predictive of outcomes in human clinical trials of the same agents.
Mammary Tumor Induction and Premature Ovarian Failure in ApcMin Mice Are Not Enhanced by Brca2 Defi ciency
Authors: Bennett L. Michelle , Mcallister Kimberly A. , Ward Toni , Malphurs Jason , Collins N. Keith , Seely John C. , Davis Barbara J. , Wiseman Roger W.
Published: July 2002

Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Apc genes. We hypothesized that if the Brca2 and Apc genes were interacting to influence mammary tumor susceptibility, then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl- N-nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Apc-mutant and Brca2/ Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7 ± 2.8 and 7.2 ± 2.7, respectively, compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1 ±0.4 and 0.3 ± 0.5, respectively. Female ENU-treated Apc-mutant and Brca2/ Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Apc mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Apc-mutant mice can progress independently of ovarian hormones. The Apc mutation-driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis.
Diagnostic Subgroups within a Sample of Comorbid Substance Abusers: Correlates and Characteristics
Authors: Toneatto Tony , Negrete Juan Carlos , Calderwood Kim
Published: July 2002

Patients seeking treatment at the Addiction Research Foundation for a substance problem but who also reported psychiatric symptomatology were referred to the Mental Health Unit. Following a clinical psychiatric interview, these patients were categorized into one of six diagnostic subgroups based on the presence of DSM‐III‐R psychiatric disorders: mood, anxiety, psychotic, organic, Axis‐II, and adjustment. A control group of patients referred to the Mental Health Unit but not diagnosed with a psychiatric disorder was also included. These groups were compared on several demographic, substance use, and psychiatric variables. Patients assigned a diagnosis of organic (substance‐induced) and A xis II disorders were found to have more severe substance use histories, alcohol‐related consequences and longer treatment histories. Patients with a diagnosis of adjustment disorder appeared to be functioning relatively better. Implications of studying the heterogeneity of comorbidity are discussed.
Intimate Partner Violence, Dependence Symptoms and Social Consequences from Drinking among White, Black and Hispanic Couples in the United States
Authors: Caetano Raul , Nelson Scott , Cunradi C.
Published: July 2002

This study estimates the association of intimate partner violence (IPV) and alcohol‐dependence symptoms, social consequences from drinking, and drug use among white, black, and Hispanic couples. A probability sample of 555 white, 358 black, and 527 Hispanic couples in the U.S. household population was interviewed in 1995. The response rate was 85%. Bivariate analysis indicates that most problem status variables are associated with increased rates of male‐to‐female (MFPV) and female‐to‐male (FMPV) partner violence. Logistic regression analyses showed that predictors of MFPV and FMPV vary by ethnicity.
Biological phenotypes associated with individuals at high risk for developing alcohol‐related disorders: Part 1
Authors: Hill Shirley Y.
Published: July 2002

This article reviews the results of studies concerning particular classes of biological phenotypes that may have relevance for alcohol dependence. Broadly defined, these classes include brain neurotransmitter systems and neuroelectric potentials. Evidence is presented concerning genotypic variation in alcoholics and high‐risk relatives suggesting that the etiology of alcoholism and other addictive diseases is mediated in part through suboptimal neurotransmitter functioning. Research opportunities are offered with respect to specific candidate genes that have been cloned from these neurotransmitter systems that could be most fully utilized in family‐based genetic analyses. Additional evidence is offered, suggesting that characteristics of particular neuroelectric potentials (e.g. the amplitude of the P300 component of the event‐related potential) may provide another dimension of potential markers that could be used to identify children at risk. Finally, methodological considerations specific to high risk studies are discussed. Among these are the need to include a plan for studying more severe cases of alcohol dependence that are relatively uncomplicated by other major psychiatric disorders. Plans for long‐term follow‐up of children at highest risk for developing the disorder should also be included. Multiple domains of inquiry should not be viewed as unfocused but rather as an economical means for utilizing highly characterized samples of individuals meeting rigorous research criteria.
Human mu opioid receptor gene polymorphisms and vulnerability to substance abuse
Authors: BERRETTINI WADE H. , HOEHE MARGRET R. , FERRARO THOMAS N. , DEMARIA PETER A. , GOTTHEIL EDWARD
Published: July 2002

Two polymorphisms of the human mu opioid receptor gene are described. A non‐coding region polymorphism (G to T) occurs at nucleotide 175 preceding the initiation of translation. A coding polymorphism in exon 1 (C to T) at nucleotide 229 changes an alanine residue to a valine residue. Frequencies of these polymorphisms were examined in groups of cocaine and/or opioid dependent individuals and matched controls. There were no significant differences between groups, although a trend (p= 0.05) towards a higher frequency of the 229 valine allele was observed in the substance abuse group, suggesting a need for large, well‐controlled studies of this polymorphism in severe substance abusers.
Alcohol consumption: a risk factor for abdominal fat accumulation in men
Authors: SUTER PAOLO M. , MAIRE RENE , VETTER WILHELM
Published: July 2002

Abstract An increased abdominal fat mass is regarded as an independent cardiovascular risk factor. In this cross‐sectional study of 1099 men we found a significant positive association between alcohol intake and the waist/hip (W/H) ratio, an index for the abdominal fat mass. This relationship was independent of age and body weight. The results suggest that the risk of abdominal fat deposition could be minimized by a reduction of alcohol intake.
The quantitative determination of R‐ and S‐salsolinol in the striatum and adrenal gland of rats selectively bred for disparate alcohol drinking
Authors: HABER H. , DUMAUAL N. , BARE D. J. , MELZIG M. F. , McBRIDE W. F. , LUMENG L. , LI T. K.
Published: July 2002

To explore the hypothesis that endogenous 1‐methyl‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline (salsolinol) might be involved in the etiology of alcoholism, its concentration was determined in the striatum and adrenal gland of rats bred selectively for disparate alcohol drinking. The alcohol‐naive alcohol‐preferring (P) and the high‐alcohol‐drinking (HAD) lines of rats demonstrated significantly lower striatal and adrenal salsolinol content when compared with the alcohol‐non‐preferring (NP) and the low‐alcohol‐drinking (LAD) lines. In the P‐line of rats, 4 weeks of free‐choice alcohol drinking had no significant effect on striatal salsolinol levels, although adrenal levels of salsolinol were significantly higher. The salsolinol assayed in the striatum of all lines of rats occurred as a racemic mixture of enantiomers that was unchanged following 4 weeks of alcohol exposure. Unlike striatal tissue, the adrenals of alcohol naive P‐rats contained significantly more S‐ than R‐salsolinol (ratio S/R = 83/17) and alcohol consumption resulted in the formation of a nearly racemic mixture of enantiomers. These results suggest a role for genetic factors in the formation of endogenous salsolinol and its potential regulation by short‐term alcohol intake.
Non‐word repetition and language development in children with specific language impairment (SLI)
Authors: Botting Nicola , Conti‐Ramsden Gina
Published: July 2002

Non‐word repetition has previously been found to correlate with language outcomes both in children who are language impaired and in those who are developing normally. This paper concerns a group of children identified as having specific language impairment (SLI) and follows the methods of Adams and Gathercole (2000) by taking children with the highest and the lowest nonword repetition scores at age 11. These children's language and literacy abilities were then compared. Despite the fact that high and low scorers were matched on Performance IQ tasks (Block Design and Picture Completion), all linguistic measures except for vocabulary assessments showed significant differences between the groups. The fact that these differences were present despite block design scores being identical for the two groups suggests that more than a general working memory deficit underlies the language difficulties. Furthermore, significant differences were noted on a digit‐span task requiring processing and production of number words. A specific phonological memory difficulty may therefore be present over and above a subtle but more general processing limitation. The implications for SLI theory and practice are discussed.
The association of parental tobacco use and SLI
Authors: Tomblin J. Bruce , Hammer Carol ScheVner , Zhang Xuyang
Published: July 2002

Studies on specific language impairments (SLI) have demonstrated that SLI aggregate in families. This may be due to the presence of prenatal and postnatal features of a shared environment, such as parental smoking, that has been associated with lowered cognitive and language outcomes in children of smokers. This study explored the relationship between parental smoking and specific language impairments (SLI) in children. Using a case‐control design, data on 177 children with SLI and 925 children who were typically developing were collected using a parental questionnaire concerning parental smoking habits. Maternal and paternal smoking during pregnancy, during children's development and continuous smoking during pregnancy and development were significantly related to SLI. However, when parental education was controlled for, these significant associations no longer existed. It is suggested that parental smoking, although not independently associated with SLI, may be an indicator of a parenting environment that places children at risk for language impairments.
Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin
Authors: Denzer Alain J. , Brandenberger Ralph , Gesemann Matthias , Chiquet Matthias , Ruegg Markus A.
Published: July 2002

Agrin is a heparan sulfate proteoglycan that is required for the formation and maintenance of neuromuscular junctions. During development, agrin is secreted from motor neurons to trigger the local aggregation of acetylcholine receptors (AChRs) and other proteins in the muscle fiber, which together compose the postsynaptic apparatus. After release from the motor neuron, agrin binds to the developing muscle basal lamina and remains associated with the synaptic portion throughout adulthood. We have recently shown that full-length chick agrin binds to a basement membrane-like preparation called Matrigel™. The first 130 amino acids from the NH2 terminus are necessary for the binding, and they are the reason why, on cultured chick myotubes, AChR clusters induced by full-length agrin are small. In the current report we show that an NH2-terminal fragment of agrin containing these 130 amino acids is sufficient to bind to Matrigel™ and that the binding to this preparation is mediated by laminin-1. The fragment also binds to laminin-2 and -4, the predominant laminin isoforms of the muscle fiber basal lamina. On cultured myotubes, it colocalizes with laminin and is enriched in AChR aggregates. In addition, we show that the effect of full-length agrin on the size of AChR clusters is reversed in the presence of the NH2-terminal agrin fragment. These data strongly suggest that binding of agrin to laminin provides the basis of its localization to synaptic basal lamina and other basement membranes.
Microphthalmia Gene Product as a Signal Transducer in cAMP-Induced Differentiation of Melanocytes
Authors: Bertolotto Corine , Abbe Patricia , Hemesath Timothy J. , Bille Karine , Fisher David E. , Ortonne Jean-Paul , Ballotti Robert
Published: July 2002

Melanocyte differentiation characterized by an increased melanogenesis, is stimulated by α-melanocyte–stimulating hormone through activation of the cAMP pathway. During this process, the expression of tyrosinase, the enzyme that controls melanin synthesis is upregulated. We previously showed that cAMP regulates transcription of the tyrosinase gene through a CATGTG motif that binds microphthalmia a transcription factor involved in melanocyte survival. Further, microphthalmia stimulates the transcriptional activity of the tyrosinase promoter and cAMP increases the binding of microphthalmia to the CATGTG motif. These observations led us to hypothesize that microphthalmia mediates the effect of cAMP on the expression of tyrosinase. The present study was designed to elucidate the mechanism by which cAMP regulates microphthalmia function and to prove our former hypothesis, suggesting that microphthalmia is a key component in cAMP-induced melanogenesis. First, we showed that cAMP upregulates the transcription of microphthalmia gene through a classical cAMP response element that is functional only in melanocytes. Then, using a dominant-negative mutant of microphthalmia, we demonstrated that microphthalmia is required for the cAMP effect on tyrosinase promoter. These findings disclose the mechanism by which cAMP stimulates tyrosinase expression and melanogenesis and emphasize the critical role of microphthalmia as signal transducer in cAMP-induced melanogenesis and pigment cell differentiation.
α-Catenin-Vinculin Interaction Functions to Organize the Apical Junctional Complex in Epithelial Cells
Authors: Watabe-Uchida Mitsuko , Uchida Naoshige , Imamura Yuzo , Nagafuchi Akira , Fujimoto Kazushi , Uemura Tadashi , Vermeulen Stefan , van Roy Frans , Adamson Eileen D. , Takeichi Masatoshi
Published: July 2002

αE-catenin, a cadherin-associated protein, is required for tight junction (TJ) organization, but its role is poorly understood. We transfected an αE-catenin–deficient colon carcinoma line with a series of αE-catenin mutant constructs. The results showed that the amino acid 326–509 domain of this catenin was required to organize TJs, and its COOH-terminal domain was not essential for this process. The 326–509 internal domain was found to bind vinculin. When an NH2-terminal αE-catenin fragment, which is by itself unable to organize the TJ, was fused with the vinculin tail, this chimeric molecule could induce TJ assembly in the αE-catenin–deficient cells. In vinculin-null F9 cells, their apical junctional organization was impaired, and this phenotype was rescued by reexpression of vinculin. These results indicate that the αE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia.
Acetylcholinesterase Clustering at the Neuromuscular Junction Involves Perlecan and Dystroglycan
Authors: Peng H. Benjamin , Xie Hongbo , Rossi Susanna G. , Rotundo Richard L.
Published: July 2002

Formation of the synaptic basal lamina at vertebrate neuromuscular junction involves the accumulation of numerous specialized extracellular matrix molecules including a specific form of acetylcholinesterase (AChE), the collagenic-tailed form. The mechanisms responsible for its localization at sites of nerve– muscle contact are not well understood. To understand synaptic AChE localization, we synthesized a fluorescent conjugate of fasciculin 2, a snake α-neurotoxin that tightly binds to the catalytic subunit. Prelabeling AChE on the surface of Xenopus muscle cells revealed that preexisting AChE molecules could be recruited to form clusters that colocalize with acetylcholine receptors at sites of nerve–muscle contact. Likewise, purified avian AChE with collagen-like tail, when transplanted to Xenopus muscle cells before the addition of nerves, also accumulated at sites of nerve–muscle contact. Using exogenous avian AChE as a marker, we show that the collagenic-tailed form of the enzyme binds to the heparan-sulfate proteoglycan perlecan, which in turn binds to the dystroglycan complex through α-dystroglycan. Therefore, the dystroglycan–perlecan complex serves as a cell surface acceptor for AChE, enabling it to be clustered at the synapse by lateral migration within the plane of the membrane. A similar mechanism may underlie the initial formation of all specialized basal lamina interposed between other cell types.
Manner of Interaction of Heterogeneous Claudin Species within and between Tight Junction Strands
Authors: Furuse Mikio , Sasaki Hiroyuki , Tsukita Shoichiro
Published: July 2002

In tight junctions (TJs), TJ strands are associated laterally with those of adjacent cells to form paired strands to eliminate the extracellular space. Claudin-1 and -2, integral membrane proteins of TJs, reconstitute paired TJ strands when transfected into L fibroblasts. Claudins comprise a multigene family and more than two distinct claudins are coexpressed in single cells, raising the questions of whether heterogeneous claudins form heteromeric TJ strands and whether claudins interact between each of the paired strands in a heterophilic manner. To answer these questions, we cotransfected two of claudin-1, -2, and -3 into L cells, and detected their coconcentration at cell–cell borders as elaborate networks. Immunoreplica EM confirmed that distinct claudins were coincorporated into individual TJ strands. Next, two L transfectants singly expressing claudin-1, -2, or -3 were cocultured and we found that claudin-3 strands laterally associated with claudin-1 and -2 strands to form paired strands, whereas claudin-1 strands did not interact with claudin-2 strands. We concluded that distinct species of claudins can interact within and between TJ strands, except in some combinations. This mode of assembly of claudins could increase the diversity of the structure and functions of TJ strands.
Lack of Pericytes Leads to Endothelial Hyperplasia and Abnormal Vascular Morphogenesis
Authors: Hellström Mats , Gerhardt Holger , Kalén Mattias , Li Xuri , Eriksson Ulf , Wolburg Hartwig , Betsholtz Christer
Published: July 2002

The association of pericytes (PCs) to newly formed blood vessels has been suggested to regulate endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching. Here, we addressed these issues using PDGF-B– and PDGF receptor-β (PDGFR-β)–deficient mice as in vivo models of brain angiogenesis in the absence of PCs. Quantitative morphological analysis showed that these mutants have normal microvessel density, length, and number of branch points. However, absence of PCs correlates with endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, changed cellular distribution of certain junctional proteins, and morphological signs of increased transendothelial permeability. Brain endothelial hyperplasia was observed already at embryonic day (E) 11.5 and persisted throughout development. From E 13.5, vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress became upregulated, suggesting that the abnormal microvessel architecture has systemic metabolic consequences. VEGF-A upregulation correlated temporally with the occurrence of vascular abnormalities in the placenta and dilation of the heart. Thus, although PC deficiency appears to have direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels may further abrogate microvessel architecture, promote vascular permeability, and contribute to formation of the edematous phenotype observed in late gestation PDGF-B and PDGFR-β knock out embryos.
Differential Dynamics of α5 Integrin, Paxillin, and α-Actinin during Formation and Disassembly of Adhesions in Migrating Cells
Authors: Laukaitis Christina M. , Webb Donna J. , Donais Karen , Horwitz Alan F.
Published: July 2002

To investigate the mechanisms by which adhesions form and disperse in migrating cells, we expressed α5 integrin, α-actinin, and paxillin as green fluorescent protein (GFP) fusions. All localized with their endogenous counterparts and did not perturb migration when expressed at moderate levels. α5-GFP also rescued the adhesive defects in CHO B2 cells, which are α5 integrin deficient. In ruffling cells, α5-GFP and α-actinin–GFP localized prominently at the leading edge in membrane protrusions. Of the three GFP fusion proteins that we examined, paxillin was the first component to appear visibly organized in protrusive regions of the cell. When a new protrusion formed, the paxillin appeared to remodel from older to newer adhesions at the leading edge. α-Actinin subsequently entered adhesions, which translocated toward the cell center, and inhibited paxillin turnover. The new adhesions formed from small foci of α-actinin–GFP and paxillin-GFP, which grew in size. Subsequently, α5 integrin entered the adhesions to form visible complexes, which served to stabilize the adhesions. α5-GFP also resided in endocytic vesicles that emanated from the leading edge of protrusions. Integrin vesicles at the cell rear moved toward the cell body. As cells migrated, α5 vesicles also moved from a perinuclear region to the base of the lamellipodium. The α5 vesicles colocalized with transferrin receptor and FM 4-64 dye. After adhesions broke down in the rear, α5-GFP was found in fibrous structures behind the cell, whereas α-actinin–GFP and paxillin-GFP moved up the lateral edge of retracting cells as organized structures and then dissipated.
Spontaneous Autoimmune Diabetes in Monoclonal T Cell Nonobese Diabetic Mice
Authors: Verdaguer Joan , Schmidt Dennis , Amrani Abdelaziz , Anderson Brad , Averill Nuzhat , Santamaria Pere
Published: July 2002

It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell–dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell–reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell–specific CD8+ and CD4+ T cells can spontaneously accumulate in pancreatic islets, differentiate into effector cells, and destroy beta cells in the absence of other T cell specificities. This was done by introducing Kd– or I-Ag7–restricted beta cell–specific T cell receptor (TCR) transgenes that are highly diabetogenic in NOD mice (8.3- and 4.1-TCR, respectively), into recombination-activating gene (RAG)-2–deficient NOD mice, which cannot rearrange endogenous TCR genes and thus bear monoclonal TCR repertoires. We show that while RAG-2−/− 4.1-NOD mice, which only bear beta cell–specific CD4+ T cells, develop diabetes as early and as frequently as RAG-2+ 4.1-NOD mice, RAG-2−/− 8.3-NOD mice, which only bear beta cell–specific CD8+ T cells, develop diabetes less frequently and significantly later than RAG-2+ 8.3-NOD mice. The monoclonal CD8+ T cells of RAG-2−/− 8.3-NOD mice mature properly, proliferate vigorously in response to antigenic stimulation in vitro, and can differentiate into beta cell–cytotoxic T cells in vivo, but do not efficiently accumulate in islets in the absence of a CD4+ T cell–derived signal, which can be provided by splenic CD4+ T cells from nontransgenic NOD mice. These results demonstrate that naive beta cell– specific CD8+ and CD4+ T cells can trigger diabetes in the absence of other T or B cell specificities, but suggest that efficient recruitment of naive diabetogenic beta cell–reactive CD8+ T cells to islets requires the assistance of beta cell–reactive CD4+ T cells.
Myelin Basic Protein–specific T Helper 2 (Th2) Cells Cause Experimental Autoimmune Encephalomyelitis in Immunodeficient Hosts Rather than Protect Them from the Disease
Authors: Lafaille Juan J. , Keere Fabienne Van de , Hsu Albert L. , Baron Jody L. , Haas Werner , Raine Cedric S. , Tonegawa Susumu
Published: July 2002

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4+ Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in αβ T cell–deficient mice, albeit after a longer preclinical phase. Normal or γδ T cell–deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.
B Lymphocytes Producing Demyelinating Autoantibodies: Development and Function in Gene-targeted Transgenic Mice
Authors: Litzenburger Tobias , Fässler Reinhard , Bauer Jan , Lassmann Hans , Linington Christopher , Wekerle Hartmut , Iglesias Antonio
Published: July 2002

We studied the cellular basis of self tolerance of B cells specific for brain autoantigens using transgenic mice engineered to produce high titers of autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface component of central nervous system myelin. We generated “knock-in” mice by replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the transgenic mice, conventional B cells reach normal numbers in bone marrow and periphery and express exclusively transgenic H chains, resulting in high titers of MOG-specific serum Igs. Additionally, about one third of transgenic B cells bind MOG, thus demonstrating the absence of active tolerization. Furthermore, peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the mature transgenic B cell population undergoes normal differentiation to plasma cells secreting MOG-specific IgG antibodies, during which both Ig isotype switching and somatic mutation occur. In naive transgenic mice, the presence of this substantial autoreactive B cell population is benign, and the mice fail to develop either spontaneous neurological disease or pathological evidence of demyelination. However, the presence of the transgene both accelerates and exacerbates experimental autoimmune encephalitis, irrespective of the identity of the initial autoimmune insult.
Neonatal Idiotypic Exposure Alters Subsequent Cytokine, Pathology, and Survival Patterns in Experimental Schistosoma mansoni Infections
Authors: Angela Montesano M. , Colley Daniel G. , Eloi-Santos Silvana , Freeman George L. , Secor W. Evan
Published: July 2002

Exposure to maternal idiotypes (Ids) or antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of schistosomiasis. We have used an experimental murine system to address the role of Ids in this immunoregulation. Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id). Newborn mice were injected with 8WkId, MSS Id, HSS Id, or normal mouse immunoglobulin (NoMoIgG) and infected with S. mansoni 8 wk later. Mice exposed to 8WkId or MSS Id as newborns had prolonged survival and decreased morbidity compared with mice that received HSS Id or NoMoIgG. When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon γ than spleen cells from mice neonatally injected with HSS Id or NoMoIgG. Furthermore, neonatal exposure to 8WkId or MSS Id, but not NoMoIgG or HSS Id, led to significantly smaller granuloma size and lower hepatic fibrosis levels in infected mice. Together, these results indicate that perinatal exposure to appropriate anti-SEA Ids induces long-term effects on survival, pathology, and immune response patterns in mice subsequently infected with S. mansoni.
Tractor calculi for parabolic geometries
Authors: Čap Andreas , Gover A.
Published: July 2002

Parabolic geometries may be considered as curved analogues of the homogeneous spaces

G

/

P

G/P

where

G
G

is a semisimple Lie group and

P
⊂
G

P\subset G

a parabolic subgroup. Conformal geometries and CR geometries are examples of such structures. We present a uniform description of a calculus, called tractor calculus, based on natural bundles with canonical linear connections for all parabolic geometries. It is shown that from these bundles and connections one can recover the Cartan bundle and the Cartan connection. In particular we characterize the normal Cartan connection from this induced bundle/connection perspective. We construct explicitly a family of fundamental first order differential operators, which are analogous to a covariant derivative, iterable and defined on all natural vector bundles on parabolic geometries. For an important subclass of parabolic geometries we explicitly and directly construct the tractor bundles, their canonical linear connections and the machinery for explicitly calculating via the tractor calculus.
Specification on the interval
Authors: Buzzi Jérôme
Published: July 2002

We study the consequences of discontinuities on the specification property for interval maps. After giving a necessary and sufficient condition for a piecewise monotonic, piecewise continuous map to have this property, we show that for a large and natural class of families of such maps (including the

β
\beta

-transformations), the set of parameters for which the specification property holds, though dense, has zero Lebesgue measure. Thus, regarding the specification property, the general case is at the opposite of the continuous case solved by A.M. Blokh (Russian Math. Surveys 38 (1983), 133–134) (for which we give a proof).
Implicitly restarted Arnoldi with purification for the shift-invert transformation
Authors: Meerbergen Karl , Spence Alastair
Published: July 2002

The need to determine a few eigenvalues of a large sparse generalised eigenvalue problem

A
x
=
λ
B
x

Ax=\lambda Bx

with positive semidefinite

B
B

arises in many physical situations, for example, in a stability analysis of the discretised Navier-Stokes equation. A common technique is to apply Arnoldi’s method to the shift-invert transformation, but this can suffer from numerical instabilities as is illustrated by a numerical example. In this paper, a new method that avoids instabilities is presented which is based on applying the implicitly restarted Arnoldi method with the

B
B

semi-inner product and a purification step. The paper contains a rounding error analysis and ends with brief comments on some extensions.
Convergence of a non-stiff boundary integral method for interfacial flows with surface tension
Authors: Ceniceros Héctor , Hou Thomas
Published: July 2002

Boundary integral methods to simulate interfacial flows are very sensitive to numerical instabilities. In addition, surface tension introduces nonlinear terms with high order spatial derivatives into the interface dynamics. This makes the spatial discretization even more difficult and, at the same time, imposes a severe time step constraint for stable explicit time integration methods. A proof of the convergence of a reformulated boundary integral method for two-density fluid interfaces with surface tension is presented. The method is based on a scheme introduced by Hou, Lowengrub and Shelley [ J. Comp. Phys. 114 (1994), pp. 312–338] to remove the high order stability constraint or stiffness. Some numerical filtering is applied carefully at certain places in the discretization to guarantee stability. The key of the proof is to identify the most singular terms of the method and to show, through energy estimates, that these terms balance one another. The analysis is at a time continuous-space discrete level but a fully discrete case for a simple Hele-Shaw interface is also studied. The time discrete analysis shows that the high order stiffness is removed and also provides an estimate of how the CFL constraint depends on the curvature and regularity of the solution. The robustness of the method is illustrated with several numerical examples. A numerical simulation of an unstably stratified two-density interfacial flow shows the roll-up of the interface; the computations proceed up to a time where the interface is about to pinch off and trapped bubbles of fluid are formed. The method remains stable even in the full nonlinear regime of motion. Another application of the method shows the process of drop formation in a falling single fluid.
On the global dynamics of attractors for scalar delay equations
Authors: McCord Christopher , Mischaikow Konstantin
Published: July 2002

A semi-conjugacy from the dynamics of the global attractors for a family of scalar delay differential equations with negative feedback onto the dynamics of a simple system of ordinary differential equations is constructed. The construction and proof are done in an abstract setting, and hence, are valid for a variety of dynamical systems which need not arise from delay equations. The proofs are based on the Conley index theory.
Verifying Kottwitz’ conjecture by computer
Authors: Casselman Bill
Published: July 2002

In these notes I will discuss the computations that were used to verify the main conjecture of Kottwitz (1997) for the groups

E

6

E_{6}

,

E

7

E_{7}

,

E

8

E_{8}

, and the subsidiary one for

F

4

F_{4}

and

E

6

E_{6}

. At the end I will include tables of the relevant computer output. I begin by recalling briefly what is to be computed.
Kazhdan-Lusztig-Polynome und eine Kombinatorik für Kipp-Moduln
Authors: Soergel Wolfgang
Published: July 2002

This article gives a selfcontained treatment of the theory of Kazhdan-Lusztig polynomials with special emphasis on affine reflection groups. There are only a few new results but several new proofs. We close with a conjectural character formula for tilting modules, which formed the starting point of these investigations.
Irreducible representations of solvable Lie superalgebras
Authors: Sergeev Alexander
Published: July 2002

The description of irreducible finite dimensional representations of finite dimensional solvable Lie superalgebras over complex numbers given by V. Kac is refined. In reality these representations are not just induced from a polarization but are twisted ones, as infinite dimensional representations of solvable Lie algebras. Various cases of irreducibility (general and of type Q) are classified.
ARL2 and BART Enter Mitochondria and Bind the Adenine Nucleotide Transporter
Authors: Sharer J. Daniel , Shern Jack F. , Van Valkenburgh Hillary , Wallace Douglas C. , Kahn Richard A.
Published: July 2002

The ADP-ribosylation factor-like 2 (ARL2) GTPase and its binding partner binder of ARL2 (BART) are ubiquitously expressed in rodent and human tissues and are most abundant in brain. Both ARL2 and BART are predominantly cytosolic, but a pool of each was found associated with mitochondria in a protease-resistant form. ARL2 was found to lack covalent N-myristoylation, present on all other members of the ARF family, thereby preserving the N-terminal amphipathic α-helix as a potential mitochondrial import sequence. An overlay assay was developed to identify binding partners for the BART·ARL2·GTP complex and revealed a specific interaction with a protein in bovine brain mitochondria. Purification and partial microsequencing identified the protein as an adenine nucleotide transporter (ANT). The overlay assay was performed on mitochondria isolated from five different tissues from either wild-type or transgenic mice deleted for ANT1. Results confirmed that ANT1 is the predominant binding partner for the BART·ARL2·GTP complex and that the structurally homologous ANT2 protein does not bind the complex. Cardiac and skeletal muscle mitochondria fromant1−/ant1−mice had increased levels of ARL2, relative to that seen in mitochondria from wild-type animals. We conclude that the amount of ARL2 in mitochondria is subject to regulation via an ANT1-sensitive pathway in muscle tissues.