Toddlers' use of metric information and landmarks to reorient.

Mobile organisms can keep track of spatial location (both their own location and that of objects in the environment) using either an external referent system or one centered on the self and updated by information about movement through space. When the latter system is disabled (e.g., by rapid turning), aspects of the external world must be used to reestablish orientation. Recently, it has been claimed that, both for rats and for human toddlers, reorientation is achieved using a geometric module that accepts only information about the metric properties of the environment (C. R. Gallistel, 1990; L. Hermer & E. S. Spelke, 1994, 1996). In a series of experiments, this paper confirms that geometric information is used for reorientation by young children, but gives reason to doubt that the use of this information is achieved using a module impenetrable to nongeometric information.

Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pK(a).

Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8-6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED(80) 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose.

pH and bicarbonate in the ductuli efferentes testis of the rat.

The pH and bicarbonate concentrations of luminal fluids in the efferent ducts of the rat were estimated from pH measurements of samples in vitro under conditions of controlled temperature and carbon dioxide tension. The pH of scrotal blood was estimated to be more acidic than systemic blood (mean pH=7.44) at either of the putative scrotal carbon dioxide tensions (5% and 7%, pH, respectively,=7.42 and 7.28). For PCO2 tensions of 5% and 7%, respectively, the data indicated that the pH in the efferent ducts was significantly higher (distal initial zone pH=7.55 or 7.41; coni vasculosi pH=7.66 or 7.51; p < 0.01) than in fluid entering (rete testis fluid, pH=7.34 or 7.20) or leaving the ducts (zone 1a of the epididymal duct 7.26 or 7.11). Bicarbonate concentrations were also significantly higher (p < 0.01) in the efferent ducts (35.4 +/- 4.7 mM, distal initial zone; 45.2 +/- 7.6 mM, coni vasculosi) than in fluids entering (22.9 +/- 3.6 mM) or leaving (20.4 +/- 4.9 mM) the ducts. Estimates of the reabsorption of bicarbonate and fluid indicated that 96% of the testicular output of bicarbonate was reabsorbed in the efferent ducts, but there was also some secretion of bicarbonate into the ducts. It is concluded that luminal pH and bicarbonate levels in the efferent ducts of the rat are high relative to those found in the epididymis where low pH and bicarbonate contributes to sperm quiescence during storage. Nevertheless, the high rate of bicarbonate reabsorption in the efferent ducts is a major contributor to the establishment of the low pH and bicarbonate milieu of the epididymis.

Elementary school children's explicit and implicit memory for faces of preschool classmates.

This study examined elementary school children's memories for faces of preschool classmates after a 3-year interval. Children recognized their former classmates at an above-chance level, but their level of recognition was significantly lower than the level shown by the preschool teachers. Children showed implicit memory of classmates by making fewer errors while performing a face-matching task in classmate conditions than in control conditions. However, the classmate advantage on the face-matching task was found to decrease across the 3-year interval. Several findings in this study pointed to functional independence of implicit and explicit memory (e.g., children's explicit recognition memory, but not implicit memory, was related to amount of time children spent together at preschool).

Increased frequency of CCR-5 delta 32 heterozygotes among long-term non-progressors with HIV-1 infection. The Australian Long-Term Non-Progressor Study Group.

BACKGROUND: The beta-chemokine receptor CCR-5 is used as a coreceptor by macrophage-tropic strains of HIV-1 to gain entry into CD4+ cells. OBJECTIVE: To determine the effect of a common 32 base-pair deletion mutation in the CCR-5 gene (CCR-5 delta 32) on progression of HIV infection to AIDS, and to assess the level of heterozygosity for this mutation in a well-defined group of long-term non-progressors (LTNP). PARTICIPANTS: Sixty-four HIV-1-infected LTNP (CD4+ T lymphocyte count > 500 x 10(6)/l after 8 years) were compared with 95 individuals infected within a similar period (1983-1986) but who had rapidly progressed to AIDS and death, and with a further 120 HIV-positive individuals with CD4+ counts < 500 x 10(6)/l. METHODS: The presence of the CCR-5 delta 32 mutation was assessed using polymerase chain reaction with primers spanning the 32 base-pair deletion. CD4+ and CD8+ counts, plasma HIV-1 RNA, p24 antigen and beta 2-microglobulin levels in LTNP carrying the CCR-5 delta 32 mutation were compared with LTNP lacking the mutation. RESULTS: A marked increase in the frequency of CCR-5 delta 32 heterozygosity was found among LTNP (35.9%) compared with rapid progressors (12.6%; P = 0.0005) and patients selected on the basis of a CD4+ T-cell count < 500 x 10(6)/l (12.5%; P = 0.0004). LTNP heterozygous for CCR-5 delta 32 had a significantly higher CD8+ T-cell count than those without the mutation (1218 versus 972 x 10(6)/l; P = 0.044). No significant correlation was observed between heterozygosity and CD4 count, viral load, p24 antigen or beta 2-microglobulin within the LTNP group. CONCLUSIONS: This study provides the strongest evidence to date for the importance of a single copy of the CCR-5 delta 32 mutation in long-term non-progression of HIV infection, which may involve, in part, CD8+ T lymphocytes.

The development of hierarchical representation of two-dimensional space.

Adults represent the location of a point in a 2-dimensional space using 2 independent dimensions. They encode location along these dimensions both at a fine-grained level and categorically. In reporting location, they combine and weight the fine-grained and categorical information. In Experiment 1, we found that children as young as 5 years use the same 2 independent dimensions in fine-grained spatial coding of location in a circle as are used by adults-radius and angle. However, categorical coding and hierarchical combination are seen only for radius, at both 5 and 7 years. The adult pattern, where angle as well as radius is coded hierarchically, emerges by 9 years. Experiment 2 shows that there is nothing intrinsically difficult about the categorical coding of angular information; when angle is the only dimension to be encoded, younger children use hierarchical coding. Changes in 2-dimensional hierarchical coding may be due to cognitive load factors and to changes in ability to assign frames of reference.

Remembering versus knowing the past: children's explicit and implicit memories for pictures.

Two studies are reported examining children's explicit and implicit memory for pictures, using measures of recognition memory and perceptual facilitation. In Experiment 1, 3-year-olds showed significant implicit memory, as assessed by perceptual facilitation in identifying blurred pictures after a 3-month delay, even though they showed no explicit memory for the pictures, as assessed by recognition. This was true even though initial exposure to the pictures had been only in clear focus. The finding was replicated in Experiment 2, which also included 5-year-olds and adults. Recognition memory and perceptual facilitation were related for adults, but not for children at either age. The data suggest that age-related improvements in explicit memory could be due, at least in part, to the realization that perceptual fluency can be an indicator of prior experience.

Treatment of cultured pancreatic B-cells with streptozotocin induces cell death by apoptosis.

Treatment of cultured pancreatic B-cells (HIT-T15 and RINm5F) with the diabetogenic drug streptozotocin resulted in a significant increase in the number of cells that became detached from the substrate during a subsequent culture period. Examination of the detached cells by fluorescence microscopy after staining with acridine orange or by electron microscopy revealed evidence of chromatin condensation and margination. Isolation and fractionation of DNA from these cells revealed a pattern of oligonucleosomal fragmentation that was not evident in untreated cells. All of these features are characteristic of entry of the cells into apoptosis and the results suggest that the diabetogenic action of streptozotocin involves induction of apoptosis in pancreatic B-cells.

The coding of spatial location in young children.

The present paper is concerned with the representation of spatial location in young children. We report six experiments which indicate that the basic framework for coding location is present early in life. Later development consists of an increasing ability to impose organization on a broad range of bounded spaces. In the first four experiments, we examined whether very young children, like adults, can locate objects in a homogeneous space, estimating by eye the location of those objects within some frame of reference. Results show that children from 16 to 24 months are able to use distance to code the location of an object hidden in a large sandbox. Coding of distance is not dependent on a juxtaposed outside landmark, nor on the child's own position. In the last two experiments, we examine whether young children, like adults, code the location of an object hierarchically--not only as being in a particular location in a bounded space, but also as being within a larger segment of that space. The pattern of bias in responding provides evidence for such two-level coding of location. The age at which children impose subdivisions on a space depends on the nature of that space. The sandbox is subdivided by 10-year-olds, but not by 4- or 6-year-olds. In contrast, a rectangle of similar shape drawn on paper is subdivided even by 4-year-olds. We argue that 16-month-olds in the sandbox studies also use hierarchical coding, treating the whole box as a category, although they do not divide it into subsections.

In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human pathogenic fungi.

Aspergillosis is a disease caused by the opportunistic pathogen Aspergillus fumigatus and other related fungi. It occurs mainly in immunosuppressed people and causes very high mortality rates. A fumigatus and other pathogenic fungi have been shown to produce a metabolite, gliotoxin, which has immunosuppressive properties in vitro, but little is known about its in vivo activity. Here we report that gliotoxin has increased toxicity in mice after irradiation. A single injection of gliotoxin delayed the recovery of immune cells after immunosuppression by sublethal irradiation by 2 weeks. Study of the morphology of cells of the thymus, spleen, and mesenteric lymph nodes by light microscopy and electron microscopy and agarose gel electrophoresis of DNA from these organs showed that the injection of gliotoxin induced apoptosis in cells of the immune system in vivo. Thus, gliotoxin does have immunosuppressive activity in vivo and could potentially play a significant role in the pathogenesis of aspergillosis and other fungal diseases.

Cellular uptake and release of the immunomodulating fungal toxin gliotoxin.

Uptake of the immunomodulating agent gliotoxin into a panel of cells using biosynthetically radiolabelled 35S toxin showed rapid association of the toxin with all cell types studied with 70-85% of the total counts in the media becoming cell associated. A difference in kinetics was observed for cell lines when compared to the primary cells thymocytes, activated T-cells and macrophages. In the latter uptake was maximal after 10-15 min and radiolabel was lost from the cells as early as 100 min. In the cell lines studied, uptake was complete in less than 1 min with no loss of label after 100 min. The exception to this was a Wilms tumour line. Analysis of the fate of gliotoxin taken up into sensitive (activated T-cells) and resistant (human fibroblast) cells by HPLC showed: (a) up to 30% of the original gliotoxin taken up by sensitive cells was released as free gliotoxin over a 22 hr period. The remainder was metabolized to inorganic sulphate; (b) in T-cells gliotoxin is reduced to the dithiol form in significant amounts and this reduction may be modulated by glutathione; and (c) no reduced gliotoxin could be detected in the resistant fibroblast cell line 27Sk even though up to 50% of the original gliotoxin was still present in the free form in these cells at 22 hr. Gliotoxin became covalently associated with macromolecules in both cell types studied. Very little free gliotoxin is released into extracellular medium by the fibroblast cell line. Gliotoxin at 500 nM was found to induce apoptosis or programmed cell death in the Wilms tumour cell line but not in any other cell line studied, and this may account for the different kinetics of release of the toxin from the Wilms tumour cell line.

Infantile amnesia: through a glass darkly.

Memory for former preschool classmates was examined in 9- and 10-year-old children using measures of both explicit and implicit memory. Yes-no recognition of faces was at low levels but was significantly above chance. Skin conductance data showed similarly low but above-chance differentiation between classmates and controls. A median split of children based on their recognition memory scores showed that children with little evidence of explicit memory for classmates were as likely to show differential skin conductance responding to faces of former classmates as were children with higher recognition scores. Infantile amnesia, like the clinical syndrome for which it is named, may not always involve complete loss of encoded information.

A longitudinal study of predictors of spatial ability in adolescent females.

This study examined the longitudinal predictability of spatial ability in late-adolescent females by retesting 11-year-old girls studied by Newcombe and Bandura at age 16. Spatial ability at age 16 was predicted longitudinally from masculinity of the ideal self on a scale of intellectually relevant attributes at age 11, wanting to be a boy at age 11, and, negatively, by feminine expressivity at age 11. No timing of puberty or lateralization effects were observed. The findings strengthen evidence that sex-related differences in spatial ability could be experientially determined, and help to focus the search for exactly how this occurs. The findings also cast doubt on the idea that sex-related differences in spatial ability could be caused by sex differences in timing of puberty or lateralization, although other biological mechanisms remain plausible.

Relational aspects of identity: late adolescents' perceptions of their relationships with parents.

This study examines the relationship between late adolescents' identity status and their memories of their relationships to their parents. One hundred male and female undergraduates completed two questionnaires. The first assessed subjects' retrospective perceptions of their affective relationships with parents across five age periods: 1 to 5 years, 5 to 10 years, 10 to 15 years, 15 to 20 years, and the present. The second questionnaire, the Extended Objective Measure of Ego Identity Status, assessed subjects' current identity status. Trend analyses revealed: (1) a significant quadratic trend in identity committed subjects' ratings of the amount of love they felt for mother across the five age periods, and (2) a significant linear trend of increasing love from mother. In contrast, uncommitted subjects showed significant linear trends of decreasing love both for and from their mothers. Results are interpreted as evidence of the importance of resolution of identity issues to the establishment of feelings of intimacy between late adolescents and their parents.

Associations of timing of puberty, spatial ability, and lateralization in adult women.

The purpose of this study was to determine whether timing of puberty is related to spatial ability in adult women, and whether, if so, the relation could be attributed to timing-related differences in hemispheric specialization and/or timing-related differences in personality and spatial activity. 53 female undergraduates were given 2 tests of spatial ability, tests of both right-hemispheric and left-hemispheric specialization using tachistoscopic procedures, several tests assessing masculinity and femininity, and a questionnaire on spatial activity. They were also asked to recall their age at menarche. Later age at menarche was associated with greater right-hemispheric advantage on the dot location task but not with higher spatial ability. Spatial ability in this sample was in fact correlated with greater left-hemispheric advantage on the dot location task, as well as with more balanced hemispheric specialization on the syllable task. It is suggested that variability in findings regarding cognitive correlates of timing of puberty may be related to variability in strategies for approaching tasks. The implications of these data for efforts to explain sex-related differences in spatial ability are discussed.

Sex role and spatial ability: an EEG study.

The purpose of this study was to examine the relationship between sex role and spatial ability using both performance and electrocortical (EEG) measures. Two hundred and fifty four subjects were given the Differential Aptitudes Space Relations Test and a short form of the Personal Attributes Questionnaire (PAQ) which gives an indication of sex role. From this initial group, 40 males and females were chosen based on sex role scores. These subjects were asked to solve additional visuo-spatial problems. Bilateral EEG measures were taken from the frontal and parietal areas. The results indicate that frontal EEG measures are related to the sex role orientation of the subjects whereas parietal EEG measures are associated with performance on the visuo-spatial task for males but not females. These results suggest that frontal and parietal EEG measures reflect different processes. Counter to the traditional hypothesis, performance on the visuo-spatial task was negatively related to masculine sex-role orientation suggesting that factors which influence spatial processing go beyond biological sex.

Britain between the wars: the historical context of Bowlby's theory of attachment.

As developmental psychology "comes of age," there is increasing interest in tracing the history of thought and research concerning children (Lomax, Kagan, and Rosenkrantz 1978; Sears 1975; Senn 1975). Such an enterprise offers the possibility of providing not only a descriptive chronicle of personal or anecdotal interest, but a basis for insights into how our ideas have been shaped by the cultural context in which they were developed. It is, for instance, by now commonplace to note that much of Freud's thought should be seen in the context of 19th-century Vienna, and that many of his perceptions may have been correct for the individuals he observed although they may fail as immutable observations of human behavior in general (see, e.g., Mitchell 1974). The present paper explores the cultural and historical context of another major theorist of child development, John Bowlby. The early origins of Bowlby's theory are sought in events set in train in Britain by the First World War, and occurring during the interwar period. This may surprise readers who think of Bowlby's work as beginning with the WHO Report (Bowlby 1951) and consequently as related to the Second World War, to observations by Burlingham and Freud (1942, 1944) of children separated from their families, and to Spitz's (Spitz and Wolf 1946) work on infants in foundling homes and orphanages. But formulations in the WHO report clearly appear in Bowlby's work before World War II and are also evident in the writings of Klein (1935, 1940) and Suttie (1935), who were working on themes first drawn into focus during the first World War. In a personal interview, Bowlby identified 1929 as the time when he was first struck by the importance of separation in children's lives. Thus, this paper focuses on the effect of the "Great War" on psychoanalytic thought and, more generally, on psychiatry in Britain.