Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation

Gastrulation marks the onset of germ layer formation from undifferentiated precursor cells maintained by a network including the Pou5f1 gene, Oct3/4. Negative regulation of the undifferentiated state is a prerequisite for germ layer formation and subsequent development. A novel cross‐regulatory network was characterized including the Pou5f1 and Cdx1 genes as part of the signals controlling the onset of gastrulation. Of particular interest was the observation that, preceding gastrulation, the Xenopus Oct3/4 factors, Oct60, Oct25, and Oct91, positively regulate Cdx1 expression through FGF signaling, and during gastrulation the Oct3/4 factors become repressors of Cdx1. Cdx1 negatively regulates the Pou5f1 genes during gastrulation, thus contributing to the repression of the network maintaining the undifferentiated state and promoting the onset of gastrulation. These regulatory interactions suggest that Oct3/4 initiates its own negative autoregulation through Cdx1 up‐regulation to begin the repression of pluripotency in preparation for the onset of gastrulation and germ layer differentiation. Developmental Dynamics 240:796–807, 2011. © 2011 Wiley‐Liss, Inc.     

Decreasing incidence and prevalence of rheumatoid arthritis in pima indians over a twenty-five—year period

Objective. To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). Methods. Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965–1990. Results. Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (P_trend = 0.225), and by 57% in women (P_trend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (P_trend = 0.63) and by 40% in women (P_trend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. Conclusion. The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.