bluuebunny/crossref_metadata_2025 huggingface dataset:
People and objects affect the quality of vocalizations in infants with down syndrome
Authors: Legerstee Maria , Bowman Thomas G. , Fels Sabina
Published: June 2007

The vocalizations of eight infants with Down syndrome were recorded longitudinally in relation to different social and non‐social contexts. The infants were observed biweekly from 8 to 24 weeks and monthly up to 40 weeks. At each visit the infants were presented with their mother, a female stranger, and a rattle puppet, each alternately active and passive. Each condition lasted 60 sec. The results showed that by 4 months of age, the infants produced different types of vocal sounds in relation to environmental contexts. They produced significantly more melodic (speechlike) sounds, vocalic (non‐speechlike) sounds, and emotional (crying, laughing and fussing) sounds when facing people than objects. By 6 months of age, these utterances began to be distinguished between mother and female stranger and active and passive adults. However, within the communicative context the overall amount of vocalic (non‐speechlike) sounds produced was larger than the amount of melodic (speechlike) sounds. It is suggested that this low output of melodic sounds in the overall vocal production of these infants may adversely affect the development of more appropriate vocal behaviour.
The effects of mothers' teasing: Do Japanese infants read their mothers' play intention in teasing?
Authors: Nakano Shigeru , Kanaya Yuko
Published: June 2007

The focus of this study was whether an infant can understand the playful intention in the mother's teasing behaviour. The mother's teasing behaviour can elicit playful interaction with the infant on the one hand, or can result in the infant's distress. In other words, teasing may function as the turning‐point in mother‐infant interaction. Thus it was hypothesized that the consequence of mothers' teasing behaviour would be positive or negative depending on the success or failure in communication of both mothers' play intention with play signs and infants' interpretation of the play signs. Subjects were 20 mothers and their infants aged from 10 to 13 months (M = 11 months) who were observed during 10 minutes of free play with toys that evoke minor surprise and/or fearfulness. Results showed that about one‐third of mothers' teasing behaviour elicited the infant's enjoyment. Especially, mothers' playful teasing accompanied by a smile or laugh led most successfully to infant enjoyment. In contrast, mothers' pretence teasing elicited no particular response from infants. These data suggest that around their first birthday infants develop some understanding of the play intention latent in mothers' teasing behaviour.
Infant cry as a graded signal: Experimental modifications of durations of pauses and expiratory sounds alter mothers' perceptions
Authors: Zeskind Philip Sanford , Wilhite Adam , Marshall Timothy R.
Published: June 2007

The purpose of this study was to examine experimentally the effects of the temporal structure of infant crying on mothers' perceptions. Eighteen mothers of young infants rated variations of a 10‐sec cry in which durations of all expiratory sounds and pauses were digitally lengthened and shortened by 50%. Results showed a general monotonic effect in which cries with increasingly shorter pauses were perceived to be more arousing, aversive, informative, and rough. Similarly, cries with short expirations were perceived to be more rhythmic and rough than cries with long expirations. The strength of the monotonic effect for pause duration on ratings of urgency interacted with the duration of expiratory sounds such that the combination of short pauses and short expirations created the greatest perceived urgency. This study replicates and extends previous findings which show that gradations in acoustic features of crying are associated with gradations in the intensity of adults' perceptions.
Fear, attachment and affiliation: The interaction of functional systems in 8‐ and 12‐month‐old infants
Authors: Baron Maria Jose Ortiz
Published: June 2007

In this research fear of strangers has been analysed as it interacts with attachment and affiliation, and in relation to developmental level, in conditions most similar to the natural situations where encounters with unfamiliar persons take place. A total of 30 infants and their mothers participated. The children were divided into two groups (8‐9 and 11‐12 months). Each infant was approached by two females, who, in turn, produced either of two natural sequences. Our results allowed us to confirm the universality of fear and its coexistence and interaction with attachment and affiliation. As far as the role that developmental level plays, it was noted that in the 12‐month‐old infants fear reactions were more intense than in the younger ones. Furthermore, the attachment system was more activated in the older group in the intrusive episodes, but when the threatening nature of the situation decreased, attachment was activated less in the 12‐month‐old group. Another difference was related to control resources. While in the younger infants we observed a tendency to control their own emotional state, the 12‐month‐old infants tried to gain control over the stranger. These results were interpreted by considering the adaptative value of an increase with age of the capacity to evaluate a situation's threat value, of attachment security, and of behavioural resources permitting some control over the stranger's behaviour.
Perceptions of maternal and paternal solicitude by birth children and adoptees: Relevance for maternal bonding theory
Authors: Silverman Irwin , Dickens Susan E. , Eals Marion , Fine Judith
Published: June 2007

This study emanated from the long‐standing question of whether a maternal bonding process similar to other mammalian species occurs in humans. The perceptions of adult adoptees and a matched sample of non‐adoptees about their parents' behaviours towards them were compared on an original Parental Solicitude Scale. As hypothesized, birth children perceived their mothers as the more solicitous parent, but ratings of adoptive mothers showed a unilateral decline. Further, the differential ratings for birth and adoptive mothers occurred mostly for the factors labelled benignity vs abuse and tolerance vs control, rather than caretaking vs neglect, which was congruent to reported effects in prior studies of lack of mother‐infant contact during the sensitive period for bonding. An alternative explanation of the data was also tested but not substantiated.
Father and mother contributions to family functioning when the child has a mental delay
Authors: Becker Patricia T. , Houser Betty J. , Engelhardt Kay F. , Steinmann Mary J.
Published: June 2007

Less is known about the father's than the mother's role in family adaptation to children with disabilities. The purpose of this study was to examine relationships of both father and mother use of coping strategies and perceptions of the child with measures of family functioning style. Subjects were 26 families of 30‐month‐old children with a mental delay and a comparison group of 26 families of same‐aged children with no delay. Functioning style for study families showed a balance of cohesion and adaptability; comparison families were more chaotically flexible on the adaptability scale. Mothers and fathers agreed on family functioning style. Study parents made the greatest use of external coping strategies, while in both groups mothers used more external and fathers more internal coping strategies. Relationships between coping and family functioning varied by parent and by group. Results suggest the need for further exploration of the separate needs of fathers and mothers in maintaining balanced family functioning.
Mother–child disputes as arenas for fostering negotiation skills
Authors: Leonard Rosemary
Published: June 2007

Valsiner's concepts of the zone of free movement (ZFM) and the zone of promoted actions (ZPA) were applied to mother‐child disputes to study how mothers discharge their role as experts in negotiation. Twenty mothers of 3‐5‐year‐olds each reported 20 disputes, 10 in which the mother was making a request and 10 in which she was refusing her child's request. The disputes were analysed sequentially using four models, preservation, copycat, reward/punishment, and provision of a rationale. The results showed that perseveration and copycat models were more likely to apply when there was negative affect. Mother's re‐requests fitted the reward/punishment model whereas mother's refusals better fitted the provision of a rationale model. Information from follow‐up interviews supported the notion that requests and refusals are being socialized differently. The results imply that, whereas children's requests and refusals are within the ZFM, only their requests are within the ZPA.
Relations between maternal network size and maternal behaviour with five‐year‐olds across levels of maternal background and child ability
Authors: Ball Ruth M. , Pianta Robert C.
Published: June 2007

The article examines the relations between mothers' reports of the size of their social support networks and observations of their behaviour with their 5‐year‐old children in a sample of 281 children entering kindergarten. Results indicate that maternal network size was correlated with mothers' competence in interaction with their children, even after controlling for variance in maternal education and child cognitive ability. Further analyses, when the sample was divided according to demographic or child risk, indicated that the relation between network size and maternal competence interaction was higher in the high‐risk groups than in the low‐risk groups. The results extend the literature on social support to large, normal samples of school‐age children and are discussed in terms of ecological models of development.
Early interactions and the socioemotional development of deaf infants
Authors: Koester Lynne Sanford
Published: June 2007

Studies of the early face‐to‐face interactions and later attachment behaviours between infants and their caregivers are reviewed, with a particular focus on implications for deaf infants. Since the majority of deaf infants are born to hearing parents, it is to be expected that many parental responses will rely on vocalizations which are inaccessible to the deaf infant. Are other sensory modalities enhanced or used in a compensatory manner by hearing parents so as to make their communication with a deaf infant more effective? Is the deaf infant's heightened need for visual and tactile input adequately met during normal interactions with their caregivers? Does the deaf infant develop the same strategies for signalling distress and coping with separation as does the hearing infant? Although the research literature on this population is sparse, there are beginning to be more reports addressing these questions as early identification becomes increasingly possible. Therefore, this paper will cover issues of the role of eye contact and mutual coordination in early interactions, compensatory parenting behaviours from the perspective of the ‘intuitive parenting’ model, and precursors to later attachment behaviours in deaf infants.
Infantile colic and parental experiences
Authors: Bohlin Gunilla , Hagekull Berit , Lindberg Lene
Published: June 2007

The study comprised two groups of 33 parents each, one whose infants were identified by parents as colicky during their first 3 months and one with non‐colicky infants. Parents filled out a questionnaire with one set of questions about parental experiences when infants were 3 months old and a set of parallel questions concerning current experiences (infant age 8‐11 months). The results showed that the 3‐month situation was more negatively described with regard to both infant behaviour and parental experiences by the parents of colicky infants. For the current situation (8‐11 months), there were no significant group differences, meaning that no long‐lasting effects could be demonstrated. However, in the colic group amount of crying and difficulty in comforting during the colic period were significantly related to current parental satisfaction, which suggests that these aspects of infant behaviour and experienced parental competence are of importance also in a longer perspective.
Patterns of 4‐month‐old infant responses to hidden silent and sounding people and objects
Authors: Legerstee Maria
Published: June 2007

Responses of 4‐month‐old infants to hidden people and objects were investigated with equated task demands. Twenty‐one 4‐month‐old infants were administered a combined task, in which they were shown a sounding stimulus that continued to sound after hiding, an auditory task, in which sound was the only source of information about the position of the object in space, and a vision task, in which a silent stimulus was shown to the infants prior to hiding. Five infant behaviours were coded: reaching, gazing, body movements, vocalizations and smiles. The infants reached significantly more for hidden objects than for people, to whom they vocalized instead. They further smiled, and moved their bodies more towards their invisible mother than to the other stimuli. Thus infants responded differentially to people and objects whether the stimuli were soundless (so that there was no cue to their presence) or not. This suggested that infants appreciated (a) that an object had been hidden; (b) this object was either animate or inanimate; and (c) different procedures were appropriate for the retrieval of, or for interacting with animate and inanimate objects. Discussion centres on the underlying representational system that allows for such appreciation.
Neonatal finger and arm movements as determined by a social and an object context
Authors: Rönnqvist Louise , von Hofsten Claes
Published: June 2007

What kind of hand and finger movements are newborn infants preoccupied with, and how are these movements organized and controlled? These questions were studied in two experiments under three conditions: a social condition, in which the mother (in expt 1) or the experimenter (in expt 2) sat face to face with the infant; an object condition, in which a ball moving slowly and irregularly was presented to the infant; and a baseline condition (in expt 1) without ball or mother present. The size of the ball and the distance to it was chosen so that it approximately corresponded to the visual angle of the head of the model. Twenty‐six neonates participated in the study ranging from 2 to 6 days of age at the time of observation. All infants were in an alert, optimal awake state during the experiments. The infants' finger movements were scored from video recordings. The result revealed a large variety of relatively independent finger movements. It was found that finger movements differed both in quantity and quality between the three conditions. There were many more finger movements in the social condition than in the object and baseline conditions. In addition, there were relatively more transitional finger movements and flexions of the hand in the social condition, and relatively more thumb‐index finger activity and extensions of the hand in the object condition. Finally, the arms were more often forward extended in the object condition than in the social condition. The results support the notion that neonates show different modes of functioning towards people and objects.
The effects of maternal employment and non‐maternal infant care on development at two and four years
Authors: Scarr Sandra , Thompson William W.
Published: June 2007

Differences in maternal employment during children's first year of life and children's entry into non‐maternal care before the age of 1 year failed to predict differences in cognitive and socioemotional development at 2 and 4 years of age, after family background variables were controlled. Two samples were studied: a population sample of 1100 Bermudian children and a smaller subsample of children most of whom were determined to be at risk for developmental problems. To assess the effects of maternal employment, we compared infants with mothers who worked 20 or more hours a week to infants with mothers who worked less than 20 hours a week. To assess the effects of entry into non‐maternal care before the age of one, we compared infants who were placed in regular non‐maternal care before the age of one versus infants who did not experience regular non‐maternal care before the age of one. The results revealed that family background variables frequently predicted many child outcome measures in both the total sample and the smaller research sample. After controlling for family characteristics, no differences were found between children whose mothers worked 20 or more hours a week when they were infants and children with mothers who worked less than 20 hours a week in either sample. In addition, age of entry into non. maternal care before the age of one did not significantly predict any child outcome measures.
What influences the quality of care in English playgroups?
Authors: Melhuish Edward C.
Published: June 2007

In a study of the quality of care, interviews and observations of 45 playgroups in three areas of England were conducted. The Early Childhood Environment Rating Scale was used as a measure of quality. The influence of area, resources, management, size, space, staffing, training, support, parental involvement and staff dissatisfaction upon quality were considered. The major influence was playgroup leader training, and parental involvement was also associated with quality of care. Parental involvement and staff training were strongly linked, indicating the confounding of family and child care characteristics and the importance of understanding family and child care interrelationships. The applicability of the measures to English playgroups was discussed.
The development of referential offering in the first year
Authors: Reinecke Mark A. , Fogel Alan
Published: June 2007

The ontogeny of referential offers was examined in a longitudinal, within dyad case study of two mother–infant pairs. A combination of microanalytic and qualitative methodologies was employed in describing the functions and morphology of this gesture, as well as its temporal and sequential organization with a number of infant and maternal behaviours. Offers were found to emerge from repetitive, exploratory play routines that provide infants with alternative visual perspectives on objects, and were facilitated by mothers' support of infants' immature attentional, motoric and arousal regulation capacities. Offers were observed to co. occur with maternal behaviours that direct and maintain infants' attention to objects. Our observations suggest that offers are transformed through guided interactions into conventional communicative gestures. Offering arises as mothers become part of the infants' exploratory play routines, gradually changing the function of the behaviour of the infants. These observations are consistent with dynamic systems models of development.
Are twins different from singletons during early childhood?
Authors: Robin Monique , Casati Irène
Published: June 2007

This paper examines the specificity of intrafamilial experiences to which twins are exposed during early childhood, and the impact of this family context on the psychological development of twins. An overview of the literature on the psychological development of twins indicates two broad categories of findings. The first category covers studies dealing with the developmental features that appear early in twins. Although there are numerous studies comparing the psychomotor and verbal development of twins to singletons, only a few have dealt with the emergence of personality and identity, and most have been conducted in clinical settings. The second set of studies deals with mother‐twin relations, explored in recent years in terms of the psychosocial stress created by twin births. Few studies have examined the mother‐twin relationship in the light of major theories on mother‐child bonding (psychoanalysis, attachment, interactionist model). These developmental models have mainly focused on mother‐infant dyads, while the construction of this specific mother‐twin relationship needs to be set within the framework of a triadic situation. Rather than describing a specific ‘twin mentality’, it is argued here that the twin situation should be seen as a special case of adaptative development, both for the mother and the child, which has effects on the formation of the individual.
Non‐directive play therapy as a means of recreating optimal infant socialization patterns
Authors: Ryan Virginia , Wilson Kate
Published: June 2007

The paper proposes that non‐directive play therapy recreates conditions similar to those created between a carer and infant during normal development. By the heightening in therapy of essentially normal developmental processes the child with harmful or inadequate relationship experiences is enabled to rework and reintegrate these into normal interactiv patterns. Ways are reviewed in which non‐directive play therapy exemplifies important attachment properties in an individual's primary relationships, and recreates healthy carer‐infant patterns of interaction such as topicsharing, face‐to‐face interactions, mutuality and symbolic play, in order to bring about therapeutic change. This primary corrective function is similar to other responsive therapeutic approaches, but it is argued that a particular strength of non‐directive play therapy lies in its inherent flexibility and responsiveness to the individual child, which resembles normal infant socialization with a sensitive carer.
Mother‐child and father‐child communication in the second year: A functional approach
Authors: Marcos Haydée
Published: June 2007

The purpose of this study was to compare young children's communication with their mother and with their father at the end of the second year. Communication was analysed in terms of the function or social goal of messages addressed to the adult. Twenty children attending day care centres were observed in a specifically planned setting. The findings showed that children (boys and girls) addressed more directives to their fathers and tended to address more expressions of reactions to objects and events (expressives) to their mothers. These differences stem in part from the spontaneous choice by the child of his or her communicative acts. As for the parents, fathers produced more action directives than mothers and mothers produced more assertives than fathers. The results are discussed in terms of (a) the capacity of young children to adapt their communicative acts to the partners' characteristics, and (b) a difference in focus of father‐child and mother‐child relationships: the former appear to be more ‘task‐oriented’ and the latter more oriented to sharing ‘descriptions’ of the inner or the outer world.
The expectation of guilt and resistance to temptation
Authors: Lake Nicholas , Lane Sophie , Harris Paul L.
Published: June 2007

Children's expectations about the emotions that surround a moral transgression were examined. In experiment 1, children aged 4‐6 years and 8‐9 years listened to a story about a child who resisted but then yielded to the temptation to take a sweet without permission. In line with earlier findings (Nunner‐Winkler and Sodian, 1988), older children were more likely than younger children to expect the wrongdoer to feel pleased at resisting, but to feel bad after yielding to, temptation. In experiment 2, the relation between expectations of emotion and actual resistance to temptation was studied. Children aged 5‐6 years again made judgements about a story character who eventually yielded to temptation. Their own resistance to temptation was assessed by means of a cheating task: children were given an opportunity to cheat by peeking during the experimenter's absence. Children who did not peek were more likely to attribute morally oriented feelings to the story protagonist. The results suggest that children who readily anticipate the emotional consequences of wrongdoing are more likely to resist the temptation to transgress.
Infant information‐processing performance and maternal education
Authors: Mayes Linda C. , Bornstein Marc H.
Published: June 2007

Relations between maternal education and indices of infant information‐processing performance were examined. A sample of 93 3‐month olds whose mothers' completed education level was adequately distributed were seen in an infant control habituation procedure. Eighteen infants failed to complete the procedure, and 76 reached a conventional habituation criterion. No significant differences in habituation performance by maternal education level emerged. This finding suggests that information‐processing indices obtained in the first 6 months are useful as predictive measures of mental development that are uncorrelated with important markers of infants' environmental rearing conditions.
Not so far from home: How family characteristics predict child care quality
Authors: Bolger Kerry E. , Scarr Sandra
Published: June 2007

This study examined the relationship between family background and child care quality for 636 children enrolled in 120 day care centres in three states in the US with widely varying regulations for child care centre quality. Family characteristics accounted for a substantial portion of the variance in day care quality. Mother' attitudes towards child‐rearing and parent' education were the most potent family‐level predictors of quality. State child care policy variables were also strong predictors of quality. Findings also suggest that the influence of environment on children's development cannot be partitioned simply into family and out‐of‐home child care effects; rather, the child care environment is an extension of the family environment, with parents determining characteristics of both.
Mothers' beliefs and children's long‐term cognitive change: A developmental task interpretation
Authors: Olthof Tjeert , Goudena Paul P. , Groenendaal Han J.
Published: June 2007

A longitudinal study was used to explore the following hypotheses concerning the relation between mothers' beliefs, their use of high distancing utterances and children's cognitive development: (1) beliefs moderate the impact of high‐distancing utterances on children's development, and (2) beliefs reflect mothers' normative expectations that motivate themselves and their children to try to satisfy them. The participants consisted of 34 children and their mothers and teachers. Results for the motherchild dialogues indicated that the distancing–cognitive performance relationship was strongest for children whose mothers had the most positive beliefs. In addition, mothers' beliefs about a 4‐year‐old child were more strongly related to children's cognitive performance at ages 6 and 10 than to cognitive performance at age 4. Characteristics of both verbal parent–child and verbal teacher–child interactions at age 4 supported a developmental task interpretation of these findings.
Persistent crying and parenting: Search for a butterfly in a dynamic system
Authors: Papoušek Mechthild , von Hofacker Nikolaus
Published: June 2007

The risks and causes of persistent crying in early infancy are discussed on the basis of a study of 61 infants referred to the Munich Interdisciplinary Research and Intervention Program for Fussy Babies for persistent crying between 1 and 6 months of age, and of a community sample of 51 infants of the same age. Particular attention was paid to pre‐verbal parent‐infant communication, the development of which was interpreted in terms of a dynamic interactional system including both regulatory and communicative predispositions in infants and intuitive competence for supporting infant predispositions in parents. Neither a gut problem nor any other single causal factor was identified for persistent crying in the majority of cases. In contrast, persistent crying was significantly associated with multiple biological and psychosocial risk factors for both parents and infants. Neurological immaturity, difficult temperament and sleep problems in infants, and impaired psychological conditions, limited resources and failures of intuitive competences in mothers were found to threaten the developmental process in infants and give rise to ‘vicious circles’ which were destabilizing the interactional systems. Increased attention to intuitive parental competences is recommended as one effective model for therapeutic interventions.
The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells
Authors: Mahajan Simmi , Cervera Ana , MacLeod Megan , Fillatreau Simon , Perona‐Wright Georgia , Meek Stephen , Smith Andrew , MacDonald Andrew , Gray David
Published: June 2007

We have addressed the role of the inducible costimulator (ICOS) in the development of T cell help for B cells and in the generation, survival and reactivation of memory CD4 T cells and B cells. We find that while T cell help for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS‐KO) mice, the IFN‐γ response is little affected, indicating a defect in helper function that is unrelated to cytokine production. In addition, the ICOS‐negative T cells do not accumulate in B cell follicles. Secondary (memory), but not primary, clonal proliferation of antigen‐specific B cells is impaired in ICOS‐KO mice, as is the generation of secondary antibody‐secreting cells. Analysis of endogenous CD4 memory cells in ICOS‐KO mice, using MHC class II tetramers, reveals normal primary clonal expansion, formation of memory clones and long‐term (10 wk) survival of memory cells, but defective expansion upon reactivation in vivo. The data point to a role of ICOS in supporting secondary, memory and effector T cell responses, possibly by influencing cell survival. The data also highlight differences in ICOS dependency of endogenous T cell proliferation in vivo compared to that of adoptively transferred TCR‐transgenic T cells.
IL‐27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
Authors: Neufert Clemens , Becker Christoph , Wirtz Stefan , Fantini Massimo C. , Weigmann Benno , Galle Peter R. , Neurath Markus F.
Published: June 2007

IL‐27 is an IL‐12‐related cytokine frequently present at sites of inflammation that can promote both anti‐ and pro‐inflammatory immune responses. Here, we have analyzed the mechanisms how IL‐27 may drive such divergent immune responses. While IL‐27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti‐inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL‐27 suppressed the development of adaptive, TGF‐β‐induced Forkhead box transcription factor p3‐positive (Foxp3+) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg development was STAT1 independent, suggesting that IL‐27 utilizes different signaling pathways to shape T cell‐driven immune responses. Our data thus demonstrate that IL‐27 controls the development of Th17 and iTreg cells via differential effects on STAT1.
OSP/claudin‐11‐induced EAE in mice is mediated by pathogenic T cells primarily governed by OSP192Y residue of major encephalitogenic region OSP179–207
Authors: Kaushansky Nathali , Hemo Reut , Eisenstein Miriam , Ben‐Nun Avraham
Published: June 2007

Pathogenic autoimmunity against oligodendrocyte‐specific protein (OSP/claudin‐11), recently implicated in multiple sclerosis (MS) pathophysiology, has been poorly investigated as compared to that against other myelin encephalitogens. Using recombinant soluble mouse OSP (smOSP) and overlapping peptides thereof, we show that smOSP‐induced chronic EAE in C57BL/6J mice is primarily associated with CD4+ T cells reactive against OSP179–207 and OSP22–46, the major and minor encephalitogenic regions, respectively, and with a predominant B cell response against OSP22–46. The encephalitogenic OSP179–207‐specific T cells recognized OSP190–202 as minimal stimulatory epitope, while minimal encephalitogenic sequence was OSP191–199. Further delineation and structural bioinformatic analysis of the major encephalitogenic region suggested four overlapping potential I‐Ab core epitopes, predicting OSP192Y as major TCR‐contact residue shared by OSP 188–196, OSP190–198, and OSP191–199 cores, albeit at different MHC‐II pockets. Accordingly, substitution at OSP192Y yielded OSP188–192A‐202, a non‐stimulatory/non‐encephalitogenic altered peptide ligand (APL) that was antagonistic for OSP188–202‐specific encephalitogenic T cells. Systemic administration of OSP188–192A‐202 suppressed OSP188–202‐induced EAE and fully reversed smOSP‐induced EAE. These data suggest that a single epitopic residue (OSP192Y) governs the selection and control of most pathogenic T cells associated with smOSP‐induced EAE in H‐2b mice. This may impact profoundly on peripheral self‐tolerance to OSP and on potential APL‐mediated therapy of OSP‐related autoimmune pathogenesis.
Sandstone dissolution landforms in the Furnas Formation, southern Brazil
Authors: Sérgio de Melo Mário , César Fonseca Giannini Paulo
Published: June 2007

The Furnas Formation (Silurian to Devonian of the Paraná Basin) consists of medium to coarse sandstones (quartzarenites) cemented by kaolinite, which reduces its porosity and makes the rock more resistant. A Mesozoic crustal upwarping called the Ponta Grossa Arch and subsequent erosion gave origin to the Devonian Scarp, which is a cuesta supported by the sandstones. The scarp serves as a boundary line for the Second Paraná Plateau, a step of the en échelon relief in the State of Paraná in southern Brazil. In the outcropping areas the sandstones display a ubiquitous phenomenon of superficial exfoliation by dissolution of the kaolinitic mesodiagenetic cement and reprecipitation of microcrystalline telodiagenetic kaolinite. The dissolution of kaolinite contributes to the development of small scale superficial landforms such as alveoles, runnels, dissolution basins, concavities at the base of rocky walls, polygonal joints, anastomosing tunnels and erosion columns. In the Quebra‐Perna River area near the Devonian Scarp, the sandstones of the Furnas Formation show many features of significant subterranean erosion, such as ‘furnas’ (collapsed hollows), ponds, wet and dry depressions, sinkholes, tunnels and grikes. Such features are associated with the presence of brittle structures (faults, fractures, dikes) in two directions: the main one, NE–SW, corresponds to reactivations of the Proterozoic basement of the Paraná Basin and the secondary one, NW–SE, runs parallel to the Ponta Grossa Arch axis. Furnas and other associated features frequently occur at the crossing of such structures. These findings indicate that the great features of subterranean erosion are the result of kaolinite dissolution, which intensifies along structural directions, in a region of scarped relief and steep hydraulic gradient. As a consequence, the Furnas Formation displays landforms that are characteristic of a both structural and karstic aquifer. Copyright © 2007 John Wiley & Sons, Ltd.
Improving power in genome‐wide association studies: weights tip the scale
Authors: Roeder Kathryn , Devlin B. , Wasserman Larry
Published: June 2007

The potential of genome‐wide association analysis can only be realized when they have power to detect signals despite the detrimental effect of multiple testing on power. We develop a weighted multiple testing procedure that facilitates the input of prior information in the form of groupings of tests. For each group a weight is estimated from the observed test statistics within the group. Differentially weighting groups improves the power to detect signals in likely groupings. The advantage of the grouped‐weighting concept, over fixed weights based on prior information, is that it often leads to an increase in power even if many of the groupings are not correlated with the signal. Being data dependent, the procedure is remarkably robust to poor choices in groupings. Power is typically improved if one (or more) of the groups clusters multiple tests with signals, yet little power is lost when the groupings are totally random. If there is no apparent signal in a group, relative to a group that appears to have several tests with signals, the former group will be down‐weighted relative to the latter. If no groups show apparent signals, then the weights will be approximately equal. The only restriction on the procedure is that the number of groups be small, relative to the total number of tests performed. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Optimal designs for two‐stage genome‐wide association studies
Authors: Skol Andrew D. , Scott Laura J. , Abecasis Gonçalo R. , Boehnke Michael
Published: June 2007

Genome‐wide association (GWA) studies require genotyping hundreds of thousands of markers on thousands of subjects, and are expensive at current genotyping costs. To conserve resources, many GWA studies are adopting a staged design in which a proportion of the available samples are genotyped on all markers in stage 1, and a proportion of these markers are genotyped on the remaining samples in stage 2. We describe a strategy for designing cost‐effective two‐stage GWA studies. Our strategy preserves much of the power of the corresponding one‐stage design and minimizes the genotyping cost of the study while allowing for differences in per genotyping cost between stages 1 and 2. We show that the ratio of stage 2 to stage 1 per genotype cost can strongly influence both the optimal design and the genotyping cost of the study. Increasing the stage 2 per genotype cost shifts more of the genotyping and study cost to stage 1, and increases the cost of the study. This higher cost can be partially mitigated by adopting a design with reduced power while preserving the false positive rate or by increasing the false positive rate while preserving power. For example, reducing the power preserved in the two‐stage design from 99 to 95% that of the one‐stage design decreases the two‐stage study cost by ∼15%. Alternatively, the same cost savings can be had by relaxing the false positive rate by 2.5‐fold, for example from 1/300,000 to 2.5/300,000, while retaining the same power. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Powerful designs for genetic association studies that consider twins and sibling pairs with discordant genotypes
Authors: Wessel Jennifer , Schork Andrew J. , Tiwari Hemant K. , Schork Nicholas J.
Published: June 2007

Genetic association studies are becoming commonplace due to the availability of cost‐effective yet sophisticated DNA sequencing and genotyping resources and technologies. In addition, technologies designed to identify molecular and subclinical phenotypes that reflect disease pathogenesis are continually being developed and refined (consider, e.g., imaging technologies, microarray‐based gene expression and proteomic platforms, histological analyses of excised tissues, etc.). Unfortunately, the large‐scale use of many of these molecular and subclinical phenotyping technologies in genetic association studies is difficult logistically and is currently cost‐prohibitive. In this paper, we consider efficient designs for testing the association between particular genetic variations and expensive, yet appropriate, subclinical phenotypes of relevance to a disease that take advantage of twins or sibling pairs discordant for genotypes at the locus (or loci) being tested. We demonstrate that including genotypically discordant twins or siblings in an association study can result in a substantial increase in power over designs that use monozygotic twins or only unrelated individuals. We ultimately argue that, from a practical standpoint, sampling from existing family or twin‐based cohorts in which: (1) follow‐up studies of a genetic association are warranted in order to assess the in vivo significance of an association with respect to more refined pathological phenotypes; and/or (2) large‐scale, genome‐wide linkage and association studies have been pursued that have focused on clinical endpoints for which the study subjects have consented to more elaborate follow‐up studies, is a powerful way to test associations. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Quantitative trait association in parent offspring trios: Extension of case/pseudocontrol method and comparison of prospective and retrospective approaches
Authors: Wheeler Eleanor , Cordell Heather J.
Published: June 2007

The case/pseudocontrol method provides a convenient framework for family‐based association analysis of case‐parent trios, incorporating several previously proposed methods such as the transmission/disequilibrium test and log‐linear modelling of parent‐of‐origin effects. The method allows genotype and haplotype analysis at an arbitrary number of linked and unlinked multiallelic loci, as well as modelling of more complex effects such as epistasis, parent‐of‐origin effects, maternal genotype and mother‐child interaction effects, and gene‐environment interactions. Here we extend the method for analysis of quantitative as opposed to dichotomous (e.g. disease) traits. The resulting method can be thought of as a retrospective approach, modelling genotype given trait value, in contrast to prospective approaches that model trait given genotype. Through simulations and analytical derivations, we examine the power and properties of our proposed approach, and compare it to several previously proposed single‐locus methods for quantitative trait association analysis. We investigate the performance of the different methods when extended to allow analysis of haplotype, maternal genotype and parent‐of‐origin effects. With randomly ascertained families, with or without population stratification, the prospective approach (modeling trait value given genotype) is found to be generally most effective, although the retrospective approach has some advantages with regard to estimation and interpretability of parameter estimates when applied to selected samples. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Expression and function of water channels (aquaporins) in migrating malignant astrocytes
Authors: McCoy Eric , Sontheimer Harald
Published: June 2007

Aquaporins (AQP) constitute the principal pathway for water movement across biological membranes. Consequently, their expression and function is important for cell volume regulation. Glioma cells quickly adjust their cell volume in response to osmotic challenges or spontaneously as they invade into the narrow and tortuous extracellular spaces of the brain. These cell volume changes are likely to engage water movements across the cell membrane through AQP. AQP expression in glioma cells is poorly understood. In this study, we examined the expression of AQP in several commonly used human glioma cell lines (D54, D65, STTG1, U87, U251) and in numerous acute patient biopsies by PCR, Western blot, and immunocytochemistry and compared them to nonmalignant astrocytes and normal brain. All glioma patient biopsies expressed AQP1, AQP4 and some expressed AQP5. However, when isolated and grown as cell lines they lose all AQP proteins except a few cell lines that maintain expression of AQP1 (D65, U251, GBM62). Reintroducing either AQP1 or AQP4 stably into glioma cell lines allowed us to show that each AQP is sufficient to restore water permeability. Yet, only the presence of AQP1, but not AQP4, enhanced cell growth and migration, typical properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential biological roles for AQP1 and AQP4 in glioma cell biology. © 2007 Wiley‐Liss, Inc.
Genetic programming approach for flood routing in natural channels
Authors: Sivapragasam C. , Maheswaran R. , Venkatesh Veena
Published: June 2007

In recognition of the non‐linear relationship between storage and discharge existing in most river systems, non‐linear forms of the Muskingum model have been proposed, together with methods to calibrate the model parameters. However, most studies have focused only on routing a typical hypothetical flood hydrograph characterized by a single peak. In this study, we demonstrate that the storage–discharge relationship adopted for the non‐linear Muskingum model is not adequate for routing flood hydrographs in natural channels, which are often characterized by multiple peaks. As an alternative, an evolutionary algorithm‐based modelling approach, i.e. genetic programming (GP), is proposed, which is found to route complex flood hydrographs accurately. The proposed method is applied for constructing a routing model for a channel reach along the Walla Walla River, USA. The GP model performs extremely well with a root‐mean‐square error (RMSE) of 0·73 m3 s−1 as against an RMSE of 3·26 m3 s−1 for routing the multi‐peaked hydrograph. The advantage of GP lies in the fact that, unlike other models, it establishes the routing relationship in an easy and simple mathematical form. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of refreezing on the isotopic composition of melting snowpack
Authors: Zhou Shiqiao , Nakawo Masayoshi , Hashimoto Shigemasa , Sakai Akiko
Published: June 2007

The isotopic composition of solid and liquid portions of natural melting snowpack is investigated in detail by the separating of liquid water from snow grains at different depths of the snowpack. The slope of the δD–δ18O line for the liquid phase is found to be lower than for the solid phase. This is proved to be due to the isotopic fractionation occurring in the melt–freeze mass exchange within the snowpack. Melting of the snowpack has no clear impact on the δD–δ18O line for the solid phase, but the slope of the δD–δ18O line for the liquid shows an overall slight decrease in the melting period. When the snowpack is refrozen, the refreezing process would inevitably cause the slope of the solid phase to decrease because of the discrepancy between the slopes of the two phases. Thus the slope of the solid would become lower and lower as the diurnal melt–freeze episodes cycle throughout the melting season. This effect is then demonstrated by looking into the isotopic composition changes of glacier firn. The extent of the effect depends on the snowpack properties and environmental conditions. The slope changes also result in a decreasing trend in deuterium excess. Copyright © 2007 John Wiley & Sons, Ltd.
Stream Macroinvertebrate Community Affected by Point‐Source Metal Pollution
Authors: Doi Hideyuki , Takagi Atsushi , Kikuchi Eisuke
Published: June 2007

The impacts of mining activities on aquatic biota have been documented in many stream ecosystems. In mining streams, point‐source heavy metal pollution often appears in the stream. We hypothesize that this pollution is toxic to macroinvertebrates owing to high concentrations of metals and therefore affects macroinvertebrate community structure. We investigated macroinvertebrate community structure in mountain streams, including heavy metal‐polluted sites and neutral‐pH streams, to determine the relationship between community structure and environmental factors such as low pH and heavy metal concentrations. Based on multidimensional scaling ordination, the macroinvertebrate community at heavy metal pollution sites was remarkably different from that at the other sites. Inductively coupled plasma mass spectrometry revealed high concentrations of aluminum and iron in surface water at the polluted sites. Macroinvertebrate community structure at the metal pollution sites was significantly different from that at other sites in the same stream and in neutral‐pH streams. Thus, point‐source metal pollution may reduce the density and diversity of in situ macroinvertebrates. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)