Regulation of the murine TRACP gene promoter

The activity of the TRACP promoter has been investigated as a model of gene regulation in osteoclasts. The murine TRACP gene promoter contains potential binding sites for a number of transcription factors in particular, candidate sites for the Ets factor PU.1 and for the microphthalmia transcription factor (MiTF). These are of relevance to osteoclast biology because the PU.1 knockout mouse has an osteopetrotic phenotype, and MiTF, when mutated in the mi/mi mouse, also results in osteopetrosis. The binding sites for both of these factors have been identified, and they have been determined to be functional in regulating TRACP expression. A novel assay system using the highly osteoclastogenic RAW/C4 subclone of the murine macrophage cell line RAW264.7 was used to perform gene expression experiments on macrophage and osteoclast cell backgrounds. We have shown that TRACP expression is a target for regulation by the macrophage/osteoclast transcription factor PU.1 and the osteoclast commitment factor MiTF and that these factors act synergistically in regulating this promoter. This directly links two controlling factors of osteoclast differentiation to the expression of an effector of cell function.

Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

Factors affecting akinete differentiation in Cylindrospermopsis raciborskii (Nostocals, Cyanobacteria)

1. Cylindrospermopsis raciborskii is a potentially toxic freshwater cyanobacterium which can produce akinetes (reproductive spores) that on germinating can contribute to future populations. To further understand factors controlling the formation of these specialised cells, the effects of diurnal temperature fluctuations (magnitude and frequency), in combination with different light intensities and phosphorus concentrations were investigated under laboratory conditions. 2. Akinete differentiation was affected by the frequency of temperature fluctuations. Maximum akinete concentrations were observed in cultures that experienced multiple diurnal temperature fluctuations. 3. Akinete concentrations increased with increasing magnitude of temperature fluctuation. A maximum akinete concentration was achieved under multiple diurnal temperature fluctuations with a magnitude of 10degreesC (25degreesC to 15degreesC). 4. A fourfold increase in light intensity (25-100 mumol m(-2) s(-1)) resulted in an approximate 14-fold increase in akinete concentration. 5. High filterable reactive phosphorus (FRP) concentrations (> 70 mug L-1) in the medium, combined with a multiple diurnal temperature fluctuation of 10degreesC, supported the development of the highest akinete concentration.

Psychosocial and non-psychosocial risk factors for the new diagnosis of diabetes in elderly women

Objectives: Determine psychosocial variables associated with the new diagnosis of diabetes in elderly women. Examine whether variables remained significant predictors after controlling for non-psychosocial risk factors and the frequency of doctor visits. Research design and methods: A longitudinal cohort study was conducted using data from 10 300 women who completed a survey in 1996 and 1999. The women were aged between 70 and 74 years of age in 1996. The were asked to provide self-reports on a number of psychosocial and non-psychosocial variables in 1996 and on whether they had been diagnosed for the first time with diabetes in the 3-year period. The relationships between the potential risk factors and new diagnosis of diabetes were examined using binary logistic regression analysis. Results: Univariate results showed that not having a current partner, having low social support and having a mental health index score in the clinical range were all associated with higher risks of being diagnosed with diabetes for the first time. However the multivariate results showed that only a mental health index score in the clinical range and not having a current partner provided unique prediction of being newly diagnosed with diabetes. Of the non-psychosocial variables measured, only having a high BMI and hypertension were associated with increased risks of new diagnosis, while there was also evidence of a U shaped relationship between alcohol consumption and new diagnosis. Even after adjusting for frequency of doctor visits and non-psychosocial risk factors, a mental health index in the clinical range proved to still be a significant risk factor. Conclusions: A score on the mental health index that is within the clinical range is an independent risk factor for the new diagnosis of diabetes in elderly women. (c) 2006 Elsevier Ireland Ltd. All rights reserved.