The Genetic Basis of Academic Achievement on the Queensland Core Skills Test and its Shared Genetic Variance with IQ

First, this study examined genetic and environmental sources of variation in performance on a standardised test of academic achievement, the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2003a). Second, it assessed the genetic correlation among the QCST score and Verbal and Performance IQ measures using the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984) Multidimensional Aptitude Battery manual. Port Huron, MI:Research Psychologist Press, Inc.]. Participants were 256 monozygotic twin pairs and 326 dizygotic twin pairs aged from 15 to 18 years (mean 17 years ± 0.4 [SD]) when achievement tested, and from 15 to 22 years (mean 16 years ± 0.4 [SD]) when IQ tested. Univariate analysis indicated a heritability for the QCST of 0.72. Adjustment to this estimate due to truncate selection (downward adjustment) and positive phenotypic assortative mating (upward adjustment) suggested a heritability of 0.76 The phenotypic (0.81) and genetic (0.91) correlations between the QCST and Verbal IQ (VIQ) were significantly stronger than the phenotypic (0.57) and genetic (0.64) correlations between the QCST and Performance IQ (PIQ). The findings suggest that individual variation in QCST performance is largely due to genetic factors and that common environmental effects may be substantially accounted for by phenotypic assortative mating. Covariance between academic achievement on the QCST and psychometric IQ (particularly VIQ) is to a large extent due to common genetic influences.     

Perceptual speed does not cause intelligence, and intelligence does not cause perceptual speed

There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of -0.44 and -0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits.     

Differences Between Treatment Seekers in an Obese Population: Medical Intervention vs. Dietary Restriction

This study examined two groups of people who were pursuing treatment for obesity: either medical intervention (a hospital group; N = 20) or support for dietary restriction (a community group; N = 18). This study addressed four questions: (1) Were there differences between the two groups in terms of their psychological distress (as measured by the Symptom Checklist)? (2) Does binge eating moderate psychological distress? (3) Do feelings of ineffectiveness moderate psychological distress? and (4) Which variables best accounted for group membership (i.e., type of treatment sought)? Results suggested that the hospital group was significantly more distressed than the community group. However, there were no differences between the two groups with respect to binge eating or feelings of ineffectiveness. These findings suggest that it is the effects of morbid obesity that are most likely to moderate psychological distress.     

Latent inhibition of conditioned odor potentiation of startle: a developmental analysis

We conducted a two-part study of age and latent inhibition in the rat. In the first part of the study, rats given odor-shock pairings at 23 or 75 days of age exhibited a potentiated startle response in the presence of the odor the following day. This effect did not occur in rats trained at 16 or 20 days of age. Odor pre-exposure on the day prior to conditioning markedly reduced the odor potentiation of startle effect in 23- and 75-day-old rats but had no effect in 16 and 20-day-olds. In the second part of the study, rats were pre-exposed to the odor at 16 or 20 days of age and then conditioned at 23 days of age. When tested the day after conditioning, these pre-exposed rats exhibited a disruption in the odor potentiation of startle effect. We compare our results with other studies of latent inhibition, and with recent studies on whether conditioned responses are appropriate to the animal's age at training or their age at test.     

Fibroblast growth factor-2 in remodeling of the developing basement membrane zone in the trachea of infant rhesus monkeys sensitized and challenged with allergen

SUMMARY: Remodeling of the epithelial basement membrane zone (BMZ) involves increased deposition of collagen, resulting in thickening of the BMZ. The current study focuses on fibroblast growth factor-2 (FGF-2) in the tracheal BMZ in house dust mite allergen (HDMA)-sensitized infant rhesus monkeys, challenged with HDMA at a time when the BMZ is undergoing active postnatal development. To detect structural changes in the BMZ, we measured collagens I, III, and V. To detect changes in the function of the BMZ, we measured immunoreactivity of the heparan sulfate proteoglycan, perlecan, and FGF-2. We found significant thickening of the tracheal BMZ (p < 0.05) with each of these parameters. We also found that all HDMA tracheal samples expressed thin focal areas of the BMZ associated with leukocyte trafficking. These areas were depleted of perlecan and FGF-2; however, increased FGF-2 immunoreactivity was present in the adjacent basal cells. We conclude that basal cells and FGF-2 are involved with significant remodeling of the BMZ in the developing trachea of infant rhesus monkeys exposed to HDMA.     

Rapid trafficking of membrane type 1-matrix metalloproteinase to the cell surface regulates progelatinase a activation

Pericellular matrix degradation during cancer invasion and inflammation is dependent on activation of progelatinase A by membrane type 1-matrix metalloproteinase (MT1-MMP); a stoichiometric concentration of tissue inhibitor of metalloproteinase-2 (TIMP-2) is required. Activation of progelatinase A has generally been considered to be a slow process occurring as a result of enhanced expression of MT1-MMP. We herein report that ConA treatment of HT1080 fibrosarcoma cells is followed by MT1-MMP-induced activation of progelatinase A on the cell surface within 1 hour. Cell surface biotinylation, immunohistochemistry, and (125)I-labeled TIMP-2 binding to cell surface MT1-MMP were used to characterize the appearance and function of MT1-MMP on the plasma membrane. Treatment of HT1080 cells with ConA resulted in increased specific binding of (125)I-labeled TIMP-2 to cell surface receptors within 5 minutes. TIMP-2 binds almost exclusively to activated MT1-MMP on the surface of HT1080 cells. MT1-MMP function at the cell surface was also accelerated by treatment of cells with cytochalasin D, an inhibitor of actin filaments, PMA, a stimulator of protein kinase C, and bafilomycin A(1), an inhibitor of lysosome/endosome function. A functional pool of intracellular MT1-MMP available for trafficking to the cell surface was demonstrated by repetitive ConA stimulation. ConA-induced expression of MT1-MMP mRNA (Northern blot analysis) in HT1080 cells was a delayed event (>6 hours). These data suggest that presynthesized MT1-MMP is sorted to a transient storage compartment (trans-Golgi network/endosomes), where it is available for rapid trafficking to the plasma membrane and cell surface proteolytic activity.     

Histopathologic analysis of atypical lesions in image-guided core breast biopsies.

Appropriate follow-up of patients with needle core breast biopsies (NCBB) showing atypical hyperplasia remains unclear because previous studies show that subsequent open biopsies in variable proportions of these patients reveal ductal carcinoma in situ (DCIS) or even invasive carcinoma, indicating significant sampling artifact. NCBB with diagnoses of atypia were morphologically classified into groups as follows: I, ALH (n = 24); II, ADH with minimal cytologic atypism (n = 90); III, atypia, other (9 columnar, 2 apocrine, 11 atypical papillary); IV, severe ADH/borderline DCIS (n = 31). Mammographic and histologic features, including the number of foci of atypia in the NCBB and the calcification span, were then correlated with presence of DCIS or invasive tumor in subsequent open excisions. Open excisional biopsies showed more severe lesions in 12% of Group I-III cases (8% in Group I, 9% in Group II, and 27% in Group III), of which 15 were DCIS and one was an invasive tubular carcinoma (0.3 cm). Of the DCIS, 60% (n = 9) were < or =5 mm, and 13 of 15 (87%) were low grade. The NCBB cavity was immediately adjacent to the more severe lesions in 88% (n = 14) of cases, in keeping with sampling error. The subset showing severe ADH with borderline nuclear features in contrast was associated with a high likelihood (63%) of DCIS in follow-up excisions. NCBB with atypical papillary features also showed a high frequency of DCIS (4/11, 36%) in subsequent open excisions. Other factors associated with more severe lesions on open biopsy included the number of atypical foci in the NCBB (>4, P <.05) and the mammographic calcification span (>2.0 cm, P <.0001). Atypical lesions diagnosed in NCBB samples are radiographically and morphologically heterogeneous, accounting for the variable frequency of DCIS or invasive neoplasm identified in subsequent open excisions, which are usually focal, low grade, and a consequence of sampling artifact (i.e., adjacent to the NCBB cavity). DCIS is more likely if microcalcifications are mammographically extensive or if atypia is multifocal or is associated with borderline cytologic features.     

Persistent electrical coupling and locomotory dysfunction in the zebrafish mutant shocked

On initial formation of neuromuscular junctions, slow synaptic signals interact through an electrically coupled network of muscle cells. After the developmental onset of muscle excitability and the transition to fast synaptic responses, electrical coupling diminishes. No studies have revealed the functional importance of the electrical coupling or its precisely timed loss during development. In the mutant zebrafish shocked (sho) electrical coupling between fast muscle cells persists beyond the time that it would normally disappear in wild-type fish. Recordings from sho indicate that muscle depolarization in response to motor neuron stimulation remains slow due to the low-pass filter characteristics of the coupled network of muscle cells. Our findings suggest that the resultant prolonged muscle depolarizations contribute to the premature termination of swimming in sho and the delayed acquisition of the normally rapid touch-triggered movements. Thus the benefits of gap junctions during early synapse development likely become a liability if not inactivated by the time that muscle would normally achieve fast autonomous function.     

Breast cancer risk associated with ovulation-stimulating drugs

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.