bluuebunny/crossref_metadata_2025 huggingface dataset:
Aquaporin-6: An intracellular vesicle water channel protein in renal epithelia
Authors: Yasui Masato , Kwon Tae-Hwan , Knepper Mark A. , Nielsen Søren , Agre Peter
Published: July 2002

All characterized mammalian aquaporins (AQPs) are localized to plasma membranes where they function chiefly to mediate water transport across cells. Here we show that AQP6 is localized exclusively in intracellular membranes in renal epithelia. By using a polyclonal antibody to the C terminus of AQP6, immunoblots revealed a major 30-kDa band in membranes from rat renal cortex and medulla. Endoglycosidase treatment demonstrated presence of an intracellular high mannose glycan on each subunit. Sequential ultracentrifugation of rat kidney homogenates confirmed that AQP6 resides predominantly in vesicular fractions, and immunohistochemical and immunoelectron microscopic studies confirmed that >98% of AQP6 is located in intracellular membrane vesicles. In glomeruli, AQP6 is present in membrane vesicles within podocyte cell bodies and foot processes. In proximal tubules, AQP6 is also abundant in membrane vesicles within the subapical compartment of segment 2 and segment 3 cells, but was not detected in the brush border or basolateral membranes. In collecting duct, AQP6 resides in intracellular membrane vesicles in apical, mid, and basolateral cytoplasm of type A intercalated cells, but was not observed in the plasma membrane. Unlike other members of the AQP family, the unique distribution in intracellular membrane vesicles in multiple types of renal epithelia indicates that AQP6 is not simply involved in transcellular fluid absorption. Moreover, our studies predict that AQP6 participates in distinct physiological functions such as glomerular filtration, tubular endocytosis, and acid-base metabolism.
Human hippocampus associates information in memory
Authors: Henke Katharina , Weber Bruno , Kneifel Stefan , Wieser Heinz Gregor , Buck Alfred
Published: July 2002

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations.
Impairments in verb morphology after brain injury: A connectionist model
Authors: Joanisse Marc F. , Seidenberg Mark S.
Published: July 2002

The formation of the past tense of verbs in English has been the focus of the debate concerning connectionist vs. symbolic accounts of language. Brain-injured patients differ with respect to whether they are more impaired in generating irregular past tenses (take–took) or past tenses for nonce verbs (wug–wugged). Such dissociations have been taken as evidence for distinct “rule” and “associative” memory systems in morphology and against the connectionist approach in which a single system is used for all forms. We describe a simulation model in which these impairments arise from damage to phonological or semantic information, which have different effects on generalization and irregular forms, respectively. The results provide an account of the bases of impairments in verb morphology and show that these impairments can be explained within connectionist models that do not use rules or a separate mechanism for exceptions.
The magical touch: Genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin
Authors: Vasioukhin Valeri , Degenstein Linda , Wise Bart , Fuchs Elaine
Published: July 2002

Gene knockout technology has provided a powerful tool for functional analyses of genes expressed preferentially in a particular tissue. Given marked similarities between human and mouse skin, such studies with epidermally expressed genes have often provided valuable insights into human genetic skin disorders. Efficient silencing of a specified gene in a temporally regulated and epidermal-specific fashion could extend functional analyses to broadly expressed genes and increase the categories of human skin disorders to which parallels could be drawn. We have generated transgenic mice expressing Cre and a fusion protein between Cre recombinase and the tamoxifen responsive hormone-binding domain of the estrogen receptor (CreER
tam
) under the control of the human keratin 14 (K14) promoter. This promoter is strongly active in dividing cells of epidermis and some other stratified squamous epithelia. With K14–Cre, transgenic embryos recombine genetically introduced
loxP
sequences efficiently and selectively in the genomes of keratinocytes that reside in embryonic day 14.5 skin, tongue, and esophagus. With K14–CreER
tam
, postnatal transgenic mice show no Cre activity until tamoxifen is administered. If orally administered, tamoxifen activates keratinocyte-specific CreER
tam
, allowing recombination of
loxP
sequences in epidermis, tongue, and esophagus. If topically administered, tamoxifen allows recombination in the area of skin where tamoxifen was applied. Finally, we show that epidermal cells harboring a Cre-dependent rearranged genome persist for many months after tamoxifen application, indicating that the epidermal stem cell population has been targeted efficiently. These tools now pave the way for testing the functional role of different somatic mutations that may exist in mosaic disorders of the skin, including squamous and basal cell carcinomas.
Host-driven population dynamics in an herbivorous insect
Authors: Ylioja Tiina , Roininen Heikki , Ayres Matthew P. , Rousi Matti , Price Peter W.
Published: July 2002

Understanding the nature and relative importance of endogenous (density-dependent) and exogenous (density-independent) effects on population dynamics remains a central problem in ecology. Evaluation of these forces has been constrained by the lack of long time series of population densities and largely limited to populations chosen for their unique dynamics (e.g., outbreak insects). Especially in herbivore populations, the relative contributions of bottom-up and top-down effects (resources and natural enemies, respectively) have been difficult to compare because population data have rarely been combined with resource measurements. The feeding scars of a wood-mining herbivorous insect (Phytobia betulaeKangas; Diptera: Agromyzidae) of birch trees (Betula pendulaandBetula pubescens) provided long time series data (47 and 65 years) of absolute abundance (larvae/tree) in replicated trees within replicated stands. Measurements of tree annual rings provided matching time series of host age and physiological status. Analyses showed a powerful exogenous effect of stand age on temporal variation in insect abundance (58 and 32% of the variance in two populations, respectively). With the additional effects of variation among trees, 77 and 64% of the total variance in abundance was attributable to exogenous bottom-up effects of host plants. Potential endogenous effects were evident as immediate linear density dependence, but only accounted for ≈10% of the total variance. Abundance ofPhytobiais primarily a function of disturbance history, which produces a mosaic of different aged birch stands that harborPhytobiapopulations of different sizes. Density-dependence tends to regulate local populations around levels determined by host suitability.
A small asparagine-rich protein required for S-allele-specific pollen rejection inNicotiana
Authors: McClure Bruce , Mou Beiquan , Canevascini Stefano , Bernatzky Robert
Published: July 2002

Although S-locus RNases (S-RNases) determine the specificity of pollen rejection in self-incompatible (SI) solanaceous plants, they alone are not sufficient to cause S-allele-specific pollen rejection. To identify non-S-RNase sequences that are required for pollen rejection, aNicotiana alatacDNA library was screened by differential hybridization. One clone, designated HT, hybridized strongly to RNA fromN. alatastyles but not to RNA fromNicotiana plumbaginifolia, a species known to lack one or more factors necessary for S-allele-specific pollen rejection. Sequence analysis revealed a 101-residue ORF including a putative secretion signal and an asparagine-rich domain near the C terminus. RNA blot analysis showed that the HT-transcript accumulates in the stigma and style before anthesis. The timing of HT-expression lags slightly behind SC10-RNase in SIN. alataSC10SC10and is well correlated with the onset of S-allele-specific pollen rejection in the style. An antisense-HT construct was prepared to test for a role in pollen rejection. Transformed (N. plumbaginifolia× SIN. alataSC10SC10) hybrids with reduced levels of HT-protein continued to express SC10-RNase but failed to reject SC10-pollen. Control hybrids expressing both SC10-RNase and HT-protein showed a normal S-allele-specific pollen rejection response. We conclude that HT-protein is directly implicated in pollen rejection.
Thermal adaptation analyzed by comparison of protein sequences from mesophilic and extremely thermophilicMethanococcusspecies
Authors: Haney Paul J. , Badger Jonathan H. , Buldak Gerald L. , Reich Claudia I. , Woese Carl R. , Olsen Gary J.
Published: July 2002

The genome sequence of the extremely thermophilic archaeonMethanococcus jannaschiiprovides a wealth of data on proteins from a thermophile. In this paper, sequences of 115 proteins fromM. jannaschiiare compared with their homologs from mesophilicMethanococcusspecies. Although the growth temperatures of the mesophiles are about 50°C below that ofM. jannaschii, their genomic G+C contents are nearly identical. The properties most correlated with the proteins of the thermophile include higher residue volume, higher residue hydrophobicity, more charged amino acids (especially Glu, Arg, and Lys), and fewer uncharged polar residues (Ser, Thr, Asn, and Gln). These are recurring themes, with all trends applying to 83–92% of the proteins for which complete sequences were available. Nearly all of the amino acid replacements most significantly correlated with the temperature change are the same relatively conservative changes observed in all proteins, but in the case of the mesophile/thermophile comparison there is a directional bias. We identify 26 specific pairs of amino acids with a statistically significant (P< 0.01) preferred direction of replacement.
Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis
Authors: Conklin Patricia L. , Norris Susan R. , Wheeler Glen L. , Williams Elizabeth H. , Smirnoff Nicholas , Last Robert L.
Published: July 2002

Vitamin C (
l
-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals. AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined. A pathway for AsA biosynthesis that features GDP-mannose and
l
-galactose has recently been proposed for plants. We have isolated a collection of AsA-deficient mutants of
Arabidopsis thaliana
that are valuable tools for testing of an AsA biosynthetic pathway. The best-characterized of these mutants (
vtc1
) contains ≈25% of wild-type AsA and is defective in AsA biosynthesis. By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the
VTC1
locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase). This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis. In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the
Arabidopsis
Genome Initiative to rapidly clone physiologically important genes.
Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody
Authors: Weiss Lola , Slavin Shimon , Reich Shoshana , Cohen Patrizia , Shuster Svetlana , Stern Robert , Kaganovsky Ella , Okon Elimelech , Rubinstein Ariel M. , Naor David
Published: July 2002

Inflammatory destruction of insulin-producing β cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4–7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44–hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.
Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria
Authors: Deng Yibin , Wu Xiangwei
Published: July 2002

Mitochondria is believed to play a central role in p53-mediated
apoptosis. However, the signal transduction pathways leading to
mitochondria remain unclear. Here, we report that translocation of Bax
protein from cytosol to mitochondria is required for p53-induced
apoptosis. Cytosolic Bax is unable to induce apoptosis,
and blocking Bax translocation inhibits cell death. Expression of Bcl-2
blocks cytochrome
c
release and apoptosis but
has no effect on Bax translocation, suggesting that Bax translocation
acts upstream of Bcl-2. We further demonstrate that Peg3/Pw1, a
protein up-regulated in p53-mediated cell death process, induces Bax
translocation independent of apoptosis. The results suggest
that Bax translocation represents an important regulatory step in
p53-mediated apoptosis, and Peg3/Pw1 functions as a modulator
downstream of p53 to regulate Bax redistribution in the cells, thus
favoring the cellular decision toward apoptosis over growth
arrest following p53 induction.
A secretedSalmonellaprotein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration
Authors: Lee Catherine A. , Silva Milton , Siber Andrew M. , Kelly Aaron J. , Galyov Edouard , McCormick Beth A.
Published: July 2002

In response toSalmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. AlthoughS. typhimuriumcan enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine whichS. typhimuriumfactors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest thatS. typhimuriumactivates a protein kinase C-dependent signal transduction pathway that orchestrates transepithelial PMN movement. We show that the type III effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial cells. Our results force us to reconsider the long-held view thatSalmonellaeffector proteins must be directly delivered into host cells from bacterial cells.
Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity
Authors: Jones Margaret E. E. , Thorburn Anne W. , Britt Kara L. , Hewitt Kylie N. , Wreford Nigel G. , Proietto Joseph , Oz Orhan K. , Leury Brian J. , Robertson Kirsten M. , Yao Shenggen , Simpson Evan R.
Published: July 2002

The aromatase-knockout (ArKO) mouse provides a useful model to
examine the role that estrogens play in development and homeostasis in
mammals. Lacking a functional
Cyp19
gene, which encodes
aromatase, the ArKO mouse cannot synthesize endogenous
estrogens. We examined the adipose depots of male and female ArKO mice,
observing that these animals progressively accumulate significantly
more intraabdominal adipose tissue than their wild-type (WT)
littermates, reflected in increased adipocyte volume at gonadal and
infrarenal sites. This increased adiposity was not due to hyperphagia
or reduced resting energy expenditure, but was associated with reduced
spontaneous physical activity levels, reduced glucose oxidation, and a
decrease in lean body mass. Elevated circulating levels of leptin and
cholesterol were present in 1-year-old ArKO mice compared with WT
controls, as were elevated insulin levels, although blood glucose
levels were unchanged. Associated with these changes, a striking
accumulation of lipid droplets was observed in the livers of ArKO
animals. Our findings demonstrate an important role for estrogen in the
maintenance of lipid homeostasis in both males and females.
Ultrasensitive magnetic biosensor for homogeneous immunoassay
Authors: Chemla Y. R. , Grossman H. L. , Poon Y. , McDermott R. , Stevens R. , Alper M. D. , Clarke J.
Published: July 2002

A technique is described for specific, sensitive, quantitative, and
rapid detection of biological targets by using superparamagnetic
nanoparticles and a “microscope” based on a high-transition
temperature dc superconducting quantum interference device (SQUID). In
this technique, a mylar film to which the targets have been bound is
placed on the microscope. The film, at room temperature and atmospheric
pressure, is typically 40 μm from the SQUID, which is at 77 K in a
vacuum. A suspension of magnetic nanoparticles carrying antibodies
directed against the target is added to the mixture in the well, and
1-s pulses of magnetic field are applied parallel to the SQUID. In the
presence of this aligning field the nanoparticles develop a net
magnetization, which relaxes when the field is turned off. Unbound
nanoparticles relax rapidly by Brownian rotation and contribute no
measurable signal. Nanoparticles that are bound to the target on the
film are immobilized and undergo Néel relaxation, producing a
slowly decaying magnetic flux, which is detected by the SQUID. The
ability to distinguish between bound and unbound labels allows one to
run homogeneous assays, which do not require separation and removal of
unbound magnetic particles. The technique has been demonstrated with a
model system of liposomes carrying the FLAG epitope. The SQUID
microscope requires no more than (5 ± 2) × 10
4
magnetic nanoparticles to register a reproducible signal.
Moderating effects of gender and age on the relationship between self‐esteem and life satisfaction in mainland Chinese
Authors: Zhang Liwei , Leung Jin‐Pang
Published: July 2002

Previous studies indicated that not only individual self‐esteem (e.g., Diener & Diener, 1995; Neto, 1993) but also collective self‐esteem (e.g., Crocker, Luhtanen, Blaine, & Broadnax, 1994; Zhang & Leung, 1999) contributed to prediction of life satisfaction. When the effects of individual and collective self‐esteems on life satisfaction have been demonstrated, a further question in life satisfaction research is that whether the relationship between self‐esteem and life satisfaction is subject to the influence of boundary conditions. The present investigation focused on moderating effects of gender and age on the relationship between self‐esteem and life satisfaction in Chinese people. Participants were 1347 Mainland Chinese (aged from 14 to 88 years, 52.3% female) from three generations. They finished the General Life Satisfaction Scale (Leung & Leung, 1992), Life Domain Satisfaction Scale (revised from Michalos, 1985), Self‐Esteem Scale (Rosenberg, 1965) and Collective Self‐Esteem Scale (Luhtanen & Crocker, 1992). Hierarchical regression analysis indicated that the relationship between collective self‐esteem and general life satisfaction was stronger for the male participants than for the female participants. The effect of individual self‐esteem on life domain satisfaction was stronger in the male group than in the female group. The effect of individual self‐esteem on life domain satisfaction was stronger in the older people than in the younger people. However the effect of collective self‐esteem on life domain satisfaction was stronger in the younger people than in the older people. These results might reflect life task differences and social expectation differences between male and female, younger and older people. Additional research is needed with other types of samples, especially with samples from some individualist cultures to see whether the results could generalize to these cultures.
Parents' structuring of children's daily lives in relation to the quality and stability of children's friendships
Authors: Allès‐Jardel Monique , Fourdrinier Célia , Roux Aurélia , Schneider Barry H.
Published: July 2002

This study focused on the implications of parents' structuring of their children's home lives for the friendships of their children. Participants were 224 elementary‐school children (108 girls and 116 boys) from four grade levels in two schools in Aix‐en‐Provence, France. Most of the families were of middle or high socio‐economic status. The participating children were seen twice during the same school year in order to assess the stability of their friendship choices and the quality of their friendships. We used Lautrey's (1989) questionnaire in order to assess the parents' styles in the structuring of family life and related child‐rearing practice. This questionnaire delineates three structuring styles: 1) rigid, characterized by considerable imposition of routines with little leeway for exceptional circumstances; 2) flexible, in which established routines can be modified as circumstances dictate; and 3) laissez‐faire, characterized by an absence of predictability and routine. We measured friendship quality by means of Friendship Quality Scale developed by Bukowski, Hoza, and Boivin (1989). This scale consists of 23 items representing five dimensions: companionship, help, security, closeness and conflict. This tool was designed to elicit children's perceptions of a specific relationship with a friend. Results indicated a significant link between parenting style and both of the dimensions of child friendship we studied. Children from homes characterized by a laissez‐faire style of parenting have friendships with more positive features than children from homes with flexible or rigid styles. We also found that friendships were generally less stable and rated as less positive than in similar studies conducted in other countries.
The Compact City: Just or Just Compact? A Preliminary Analysis
Authors: Burton Elizabeth
Published: July 2002

The aim of the research described in this paper is to examine the validity of the claims that higher-density urban form promotes social equity—that is, promotes benefits for the life-chances of low-income groups. Overall, the evidence suggests that, for medium-sized English cities, higher urban densities may be positive for some aspects of social equity and negative for others. More specifically, likely benefits include improved public transport, reduced social segregation and better access to facilities, while the main problems are likely to be reduced living space and a lack of affordable housing. Investigations of different aspects of density show that the cities that most support social equity appear to be those that have a large proportion of high-density housing.
The road to freedom: Quantitative developmental methodology in the third millennium
Authors: von Eye Alexander , Schuster Christof
Published: July 2002

In this article we ask three questions. First, what is the relationship between substantive psychological research and research in the area of applied quantitative, statistical methods? Second, what is the development that applied quantitative methodology will undergo in the foreseeable future? Third, will this development affect the future of psychological research? The answers to these questions are cast in terms of six trends and three anticipated problems. The trends are: (1) increase in the number of available statistical methods; (2) substantive thinking triggers the development of new statistical methods; (3) statistical methods become increasingly flexible; (4) computers do the thinking; (5) there will be new paradigms such as the person-oriented perspective; and (6) statistical methods will be custom-tailored to substantive questions. The general tenor of the discussion of these trends is that the number of possibilities will increase and the researcher will be freed from method-specific constraints. The three problem trends are: (1) the choice between methods of analysis becomes increasingly difficult; (2) cases of misuse of statistics will become more frequent; and (3) the role of the methodologist will change such that more substantive knowledge will be required. In addition, issues of training of methodologists and financing research are discussed. The general outlook is depicted as encouraging.
A comprehensive model of the development of mental handicap in children treated for acute lymphoblastic leukaemia: A synthesis of the literature
Authors: Robaey Philippe , Dobkin Patricia , Leclerc Jean-Marie , Cyr Francine , Sauerwein Catherine , Théorêt Yves
Published: July 2002

Most clinical studies addressing sequelae in children with leukaemia are not theory-driven. Nonetheless, the role of different mediating biological (e.g. cranial irradiation, chemotherapy) and psychosocial variables (e.g. family functioning) has been empirically acknowledged. In these studies, a cause-effect relationship between biological variables and cognitive deficits, sometimes complex due to multiple agents, has been hypothesised. As for the psychosocial consequences, adaptation to the cancer-related stress has been the main focus, at both the individual and family levels. In this paper, we advocate the use of a global model for the development of handicap, derived from the International Classification of Impairments, Disabilities and Handicaps (ICIDH) by the World Health Organisation. This revised model proposes that handicap is the result of complex interactions between the characteristics of a person’s impairment, disabilities, and the characteristics of the environment. At each of these levels, risk/resilience factors are defined. This means that depending on the environmental obstacles they face, persons with an impairment or a disability may or may not experience a situation creating a handicap which is no longer seen as a stable status resulting from a disease to which the individual must adapt. By reviewing animal and clinical studies, current knowledge pertaining to leukaemia sequelae are integrated into the different levels defined by the model: organic impairment, disabilities, environmental obstacles, and handicap situation. Practical implications for research, policies, and individual treatments, and comparisons with existing models, are also outlined.
Social acceptance of children with mental retardation: Testing the contact hypothesis with an Italian sample
Authors: Manetti Mara , Schneider Barry H. , Siperstein Gary
Published: July 2002

The purpose of this study was to explore the acceptance of peers with mental retardation (MR) in an Italian elementary school hosting a cluster of pupils with severe and profound MR. A similar school in which most pupils have little regular contact with children with disabilities participated for purposes of comparison. To assess social acceptance, we presented photographs of hypothetical children together with vignettes describing the protagonists’ social behaviour. Respondents indicated how likely they would be to include the hypothetical child in social activities and which of the adjectives on a checklist they would ascribe to the child. Although most of the participants responded that they would include the hypothetical child in most social activities, sociometrics revealed that ” ve of the six children with moderate disabilities who were integrated in the regular classes of both schools were rejected socially.
Body movement, presence of parents, and the process of falling asleep in toddlers
Authors: Lotan Nava , Yirmiya Nurit
Published: July 2002

A total of 30 toddlers were videotaped as they fell asleep and the kinematic properties of their movements were analysed employing a computerised system, based on the Kestenberg Movement Profile (KMP). We analysed the movements and their association to the length of the falling asleep phase and presence of parents. Results revealed that the movement variables had a significant contribution in explaining the length of the Falling Asleep Phase (FAP). Toddlers who fell asleep within 30 minutes of entering bed displayed movements characterised by low amplitude and gradual slopes, movements such as sucking and caressing. Toddlers who were awake for longer than 30 minutes before they fell asleep displayed movements characterised by high amplitude and abrupt changes, movements such as kicking, banging, and straining. The movement variables predicted the length of the falling asleep phase significantly better than other variables associated with the falling asleep phase, such as duration of music played, duration of using pacifiers/thumbs, and the presence of objects in the bed including bottles. A significant correlation was found between the presence of parents in the toddler’s room and the type of movement that was used; Parents who spent more time in the room had toddlers who revealed less soothing movements and more movements characterised by high amplitudes and abrupt slopes. Possible intervening variables including temperament, chronological age, mental age, sleep parameters, and demographic information did not explain the findings. Practical applications of the study in assisting young children in the falling asleep phase are discussed.
The Social Behaviour of 11- to 12-year-old Children Born as Low Birthweight and/or Premature Infants
Authors: Tessier Réjean , Nadeau Line , Boivin Michel , Tremblay Richard E.
Published: July 2002

Two studies (Study 1 and Study 2) were carried out to compare the social behaviour of school-aged children born as premature and/or low birthweight infants, with that of children born as healthy fullterm infants. Participants in Study 1 were 147 11-year-olds of whom 49 (29 females and 20 males) were reported by their parents to have been born prematurely. Participants in Study 2 were 84 11-year-old boys, 28 of whom were born with a birthweight less than 2000 grams. These at-risk subjects were followed for a period of two years. Subgroups within both study groups were matched with control groups using gender, age, and the school environment as common factors. Children in the target classes of Study 1 were classified using the Revised Class Play (Masten, Morison, & Pelligrini, 1985) and the Peer Nomination Inventory (Perry, Kusel, & Perry, 1988). In Study 2, the children completed the Pupil Evaluation Inventory (PEI) (Pekarik, Prinz, Liebert, Weintraub, & Neale, 1976). Findings suggest that aggressive behaviour is not related to birth status and that birth status is not linked to prosocial behaviour associated with sociability and likeability. However, both studies showed that children (boys and girls alike) born as premature or low birthweight infants, expressed greater levels of internalised social behaviour. These findings suggest that infants born premature and/or with a low birthweight may be less socially competent with their peers during their school-age years.
Patterns of Social Relationships and Psychological Well-being among the Elderly
Authors: Takahashi Keiko , Tamura Junko , Tokoro Makiko
Published: July 2002

On the premise that social relationships among elderly adults differ in terms of the most significant, dominant figure, this study aimed to examine: (1) whether there were qualitative differences in supportive functions between family-dominant and friend-dominant affective relationships, and (2) whether “lone wolves”, who were deficient in human resources, had difficulties in maintaining their well-being. A total of 148 Japanese, over the age of 65, both living in communities and in institutions were individually interviewed about their social relationships using a self-report type method, the Picture Affective Relationships test, and their well-being was assessed using Depression, Self-esteem, Life satisfaction, and Subjective health scales. Results showed that there were no differences in psychological well-being between family-dominant and friend-dominant participants, but those who lacked affective figures had lower scores in subjective well-being than did their family-dominant and friend-dominant counterparts. The generalisation of these findings to other cultures is discussed.
Leaving Home Transition in Israel: Changes in Parent-Adolescent Relationships and Adolescents’ Adaptation to Military Service
Authors: Mayseless Ofra , Hai Ilan
Published: July 2002

The transition from adolescence to adulthood includes, for most young adults, physical separation from their parents in order to live away from home (Moore, 1987). This physical separation was found to be associated with positive changes in the parent-adolescent relationship (Sullivan & Sullivan, 1980). The present study extended previous findings by examining the effects of physical separation from one’s parents in the Israeli culture, where the time of home-leaving is based on the youngster’s age (18) and is not chosen by the parents or the adolescent, and where the transition is into mandatory military service. A group of 143 young men participated in the study and filled out questionnaires regarding their relationships with their parents and their adjustment and coping at two points in time: three months before conscription and three months later, following their basic training period in the army. Relationships with mothers and fathers were reported to improve (more warmth, less confrontation, and more autonomy) between the two times of measurement. Baseline level (Time l) relationships with parents contributed significantly to reported coping and adjustment. In addition, changes in relationships with parents, in particular a decrease in confrontation with parents and an increase in autonomy granted by parents, all significantly contributed to an increase in feelings of control and adjustment. Results are discussed in the light of the importance of relationships with primary caregivers (i.e. parents) and developmental changes in these relationships in promoting adjustment in early adulthood during home leaving transition.
An Evaluation of Genotoxicity Tests With Aquateric® Aqueous Enteric Coating
Authors: Batt Kathryn J. , Kotkoskie Lois A.
Published: July 2002

The genotoxic potential of Aquateric® Aqueous Enteric Coating was evaluated in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test. Aquateric was not mu-tagenic when tested in Salmonella typhimurium cell strains TA98, TA100, TA1535, TA1537, TA1538, with or without metabolic activation. A mouse lymphoma assay was conducted at concentrations ranging from 116 to 2000 μg/ml and 116 to 1250 μg/ml in the absence and presence of metabolic activation, respectively. No increased mutant frequencies were noted for any concentration tested. Aquateric was tested in the mouse micronucleus assay at a single oral dose of 7200 mg/kg Aquateric (equivalent to 5000 mg/kg cellulose acetate phthalate, the major ingredient) and bone marrow was harvested at 24, 48, and 72 hours after treatment. There was no significant increase in the number of mouse bone marrow mi-cronucleated polychromatic erythrocytes in Aquateric-treated animals at any of the harvest times. Based on the negative results in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test, it was concluded that Aquateric is not genotoxic.
Ecological Risk Assessment at the Department of Energy: An Evolving Process
Authors: Burger Joanna
Published: July 2002

The United States Department of Energy (DOE) has facilities in 34 states, and many of these have chemical or radiological contami-nation that provides a potential risk to human or ecological health. Over the next few decades many of these sites will be cleaned up, and ecological risk assessment will be one tool used to make decisions about remediation and future land use. The DOE has developed an overall strategy for making remediation decisions that involves using risk assessment, with stakeholder input, although the final decisions are the Departments. The key elements of its ecological risk assessments involve valuing the severity and likelihood of occurrence of adverse ecological effects. It is currently using a process that incorporates descriptions of the environmental risk, and valuations of the severity and likelihood of an adverse outcome before, during, and after any remedial activity. The primary difficulty with the current DOE approach to risk has been a failure to use existing information to identify either species of concern or unique habitats at risk, and a lack of uniformity across the DOE complex. Nonetheless, the inclusion of ecological risk assessment in the decision-making process will help achieve one of the new missions of DOE: the protection and maintenance of biodiversity and healthy ecosystems at sites under its control.
Monocyte Adhesion to Activated Aortic Endothelium: Role of L-Selectin and Heparan Sulfate Proteoglycans
Authors: Giuffrè Laura , Cordey Anne-Sophie , Monai Natacha , Tardy Yanik , Schapira Marc , Spertini Olivier
Published: July 2002

This study examines the role of L-selectin in monocyte adhesion to arterial endothelium, a key pathogenic event of atherosclerosis. Using a nonstatic (rotation) adhesion assay, we observed that monocyte binding to bovine aortic endothelium at 4°C increased four to nine times upon endothelium activation with tumor necrosis factor (TNF)-α. mAb-blocking experiments demonstrated that L-selectin mediates a major part (64 ± 18%) of monocyte attachment. Videomicroscopy experiments performed under flow indicated that monocytes abruptly halted on 8-h TNF-α–activated aortic endothelium, ∼80% of monocyte attachment being mediated by L-selectin. Flow cytometric studies with a L-selectin/IgM heavy chain chimeric protein showed calcium-dependent L-selectin binding to cytokine-activated and, unexpectedly, unactivated aortic cells. Soluble L-selectin binding was completely inhibited by anti–L-selectin mAb or by aortic cell exposure to trypsin. Experiments with cycloheximide, chlorate, or neuraminidase showed that protein synthesis and sulfate groups, but not sialic acid residues, were essential for L-selectin counterreceptor function. Moreover, heparin lyases partially inhibited soluble L-selectin binding to cytokine-activated aortic cells, whereas a stronger inhibition was seen with unstimulated endothelial cells, suggesting that cytokine activation could induce the expression of additional ligand(s) for L-selectin, distinct from heparan sulfate proteoglycans. Under flow, endothelial cell treatment with heparinase inhibited by ∼80% monocyte attachment to TNF-α–activated aortic endothelium, indicating a major role for heparan sulfate proteoglycans in monocyte–endothelial interactions. Thus, L-selectin mediates monocyte attachment to activated aortic endothelium, and heparan sulfate proteoglycans serve as arterial ligands for monocyte L-selectin.
Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin
Authors: Garver Timothy D. , Ren Qun , Tuvia Shmuel , Bennett Vann
Published: July 2002

This paper presents evidence that a member of the L1 family of ankyrin-binding cell adhesion molecules is a substrate for protein tyrosine kinase(s) and phosphatase(s), identifies the highly conserved FIGQY tyrosine in the cytoplasmic domain as the principal site of phosphorylation, and demonstrates that phosphorylation of the FIGQY tyrosine abolishes ankyrin-binding activity. Neurofascin expressed in neuroblastoma cells is subject to tyrosine phosphorylation after activation of tyrosine kinases by NGF or bFGF or inactivation of tyrosine phosphatases with vanadate or dephostatin. Furthermore, both neurofascin and the related molecule Nr-CAM are tyrosine phosphorylated in a developmentally regulated pattern in rat brain. The FIGQY sequence is present in the cytoplasmic domains of all members of the L1 family of neural cell adhesion molecules. Phosphorylation of the FIGQY tyrosine abolishes ankyrin binding, as determined by coimmunoprecipitation of endogenous ankyrin and in vitro ankyrin-binding assays. Measurements of fluorescence recovery after photobleaching demonstrate that phosphorylation of the FIGQY tyrosine also increases lateral mobility of neurofascin expressed in neuroblastoma cells to the same extent as removal of the cytoplasmic domain. Ankyrin binding, therefore, appears to regulate the dynamic behavior of neurofascin and is the target for regulation by tyrosine phosphorylation in response to external signals. These findings suggest that tyrosine phosphorylation at the FIGQY site represents a highly conserved mechanism, used by the entire class of L1-related cell adhesion molecules, for regulation of ankyrin-dependent connections to the spectrin skeleton.
The MAL Proteolipid Is Necessary for Normal Apical Transport and Accurate Sorting of the Influenza Virus Hemagglutinin in Madin-Darby Canine Kidney Cells
Authors: Puertollano Rosa , Martín-Belmonte Fernando , Millán Jaime , del Carmen de Marco María , Albar Juan P. , Kremer Leonor , Alonso Miguel A.
Published: July 2002

The MAL (MAL/VIP17) proteolipid is a nonglycosylated integral membrane protein expressed in a restricted pattern of cell types, including T lymphocytes, myelin-forming cells, and polarized epithelial cells. Transport of the influenza virus hemagglutinin (HA) to the apical surface of epithelial Madin-Darby canine kidney (MDCK) cells appears to be mediated by a pathway involving glycolipid- and cholesterol- enriched membranes (GEMs). In MDCK cells, MAL has been proposed previously as being an element of the protein machinery for the GEM-dependent apical transport pathway. Using an antisense oligonucleotide-based strategy and a newly generated monoclonal antibody to canine MAL, herein we have approached the effect of MAL depletion on HA transport in MDCK cells. We have found that MAL depletion diminishes the presence of HA in GEMs, reduces the rate of HA transport to the cell surface, inhibits the delivery of HA to the apical surface, and produces partial missorting of HA to the basolateral membrane. These effects were corrected by ectopic expression of MAL in MDCK cells whose endogenous MAL protein was depleted. Our results indicate that MAL is necessary for both normal apical transport and accurate sorting of HA.
Role of Tetanus Neurotoxin Insensitive Vesicle-Associated Membrane Protein (Ti-Vamp) in Vesicular Transport Mediating Neurite Outgrowth
Authors: Martinez-Arca Sonia , Alberts Philipp , Zahraoui Ahmed , Louvard Daniel , Galli Thierry
Published: July 2002

How vesicular transport participates in neurite outgrowth is still poorly understood. Neurite outgrowth is not sensitive to tetanus neurotoxin thus does not involve synaptobrevin-mediated vesicular transport to the plasma membrane of neurons. Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] attachment protein [SNAP] receptor), involved in transport to the apical plasma membrane in epithelial cells, a tetanus neurotoxin-resistant pathway. Here we show that TI-VAMP is essential for vesicular transport-mediating neurite outgrowth in staurosporine-differentiated PC12 cells. The NH2-terminal domain, which precedes the SNARE motif of TI-VAMP, inhibits the association of TI-VAMP with synaptosome-associated protein of 25 kD (SNAP25). Expression of this domain inhibits neurite outgrowth as potently as Botulinum neurotoxin E, which cleaves SNAP25. In contrast, expression of the NH2-terminal deletion mutant of TI-VAMP increases SNARE complex formation and strongly stimulates neurite outgrowth. These results provide the first functional evidence for the role of TI-VAMP in neurite outgrowth and point to its NH2-terminal domain as a key regulator in this process.
MUP-4 is a novel transmembrane protein with functions in epithelial cell adhesion in Caenorhabditis elegans
Authors: Hong Leexan , Elbl Tricia , Ward James , Franzini-Armstrong Clara , Rybicka Krystyna K. , Gatewood Beth K. , Baillie David L. , Bucher Elizabeth A.
Published: July 2002

Tissue functions and mechanical coupling of cells must be integrated throughout development. A striking example of this coupling is the interactions of body wall muscle and hypodermal cells in Caenorhabditis elegans. These tissues are intimately associated in development and their interactions generate structures that provide a continuous mechanical link to transmit muscle forces across the hypodermis to the cuticle. Previously, we established that mup-4 is essential in embryonic epithelial (hypodermal) morphogenesis and maintenance of muscle position. Here, we report that mup-4 encodes a novel transmembrane protein that is required for attachments between the apical epithelial surface and the cuticular matrix. Its extracellular domain includes epidermal growth factor-like repeats, a von Willebrand factor A domain, and two sea urchin enterokinase modules. Its intracellular domain is homologous to filaggrin, an intermediate filament (IF)-associated protein that regulates IF compaction and that has not previously been reported as part of a junctional complex. MUP-4 colocalizes with epithelial hemidesmosomes overlying body wall muscles, beginning at the time of embryonic cuticle maturation, as well as with other sites of mechanical coupling. These findings support that MUP-4 is a junctional protein that functions in IF tethering, cell–matrix adherence, and mechanical coupling of tissues.