Combining Network Modeling and Gene Expression Microarray Analysis to Explore the Dynamics of Th1 and Th2 Cell Regulation

Two T helper (Th) cell subsets, namely Th1 and Th2 cells, play an important role in inflammatory diseases. The two subsets are thought to counter-regulate each other, and alterations in their balance result in different diseases. This paradigm has been challenged by recent clinical and experimental data. Because of the large number of genes involved in regulating Th1 and Th2 cells, assessment of this paradigm by modeling or experiments is difficult. Novel algorithms based on formal methods now permit the analysis of large gene regulatory networks. By combining these algorithms with in silico knockouts and gene expression microarray data from human T cells, we examined if the results were compatible with a counter-regulatory role of Th1 and Th2 cells. We constructed a directed network model of genes regulating Th1 and Th2 cells through text mining and manual curation. We identified four attractors in the network, three of which included genes that corresponded to Th0, Th1 and Th2 cells. The fourth attractor contained a mixture of Th1 and Th2 genes. We found that neither in silico knockouts of the Th1 and Th2 attractor genes nor gene expression microarray data from patients with immunological disorders and healthy subjects supported a counter-regulatory role of Th1 and Th2 cells. By combining network modeling with transcriptomic data analysis and in silico knockouts, we have devised a practical way to help unravel complex regulatory network topology and to increase our understanding of how network actions may differ in health and disease

Obstetric Outcomes in Women with Turner Karyotype.

Context: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. Objective: This study compared obstetric outcome in women with TS karyotype with women in the general population. Design: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. Results: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. Conclusions: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls

Socioeconomic Inequalities in Hearing Loss in a Healthy Population Sample: The HUNT Study

We assessed socioeconomic position and hearing loss in a Norwegian population of 17 593 men and women aged 30–54 years in 1984–1986 who were followed for 11 years. We used analysis of variance, logistic regression, and population-attributable fraction analyses to examine associations. Significant socioeconomic inequalities in hearing loss were found among men. Adjusted odds ratios for hearing loss were approximately 1.3 to 1.9 for semi- and unskilled manual workers compared with participants with high occupational class; the population-attributable fraction of the prevalence of hearing loss over the cutpoint in the high-frequency (3, 4, 6, and 8 kHz) range was 35%