The regulatory landscape of osteogenic differentiation.

Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes.

A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome.

The Gli proteins are the transcriptional effectors of the mammalian Hedgehog signaling pathway. In an unusual mechanism, the proteasome partially degrades or processes Gli3 in the absence of Hedgehog pathway stimulation to create a Gli3 fragment that opposes the activity of the full-length protein. In contrast, Gli1 is not processed but degraded completely, despite considerable homology with Gli3.

Targeting proteins for degradation.

Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cell to avoid toxicity. The concentrations of regulatory proteins are adjusted by degradation at the appropriate time.

Mixing rules for multicomponent mixture mass diffusion coefficients and thermal diffusion factors.

Mixing rules are derived for mass diffusion coefficient and thermal diffusion factor matrices by developing compatibility conditions between the fluid mixture equations obtained from nonequilibrium thermodynamics and Grad's 13-moment kinetic theory. The mixing rules are shown to be in terms of the species mole fractions and binary processes. In particular, the thermal diffusion factors for binary mixtures obtained by the Chapman-Enskog expansion procedure are suitably generalized for many-component mixtures.

Changing incidence and delay of testicular cancer in southern Norway (1981-1992).

Methods: The medical records of 352 patients with newly diagnosed testicular cancer were reviewed. Patients were orchiectomized during three 2-year periods (1981/82, 1986/87, 1991/92) and were referred for further treatment to the Norwegian Radium Hospital. They represented 96% of all cases with unilateral testicular cancer occurring within a defined area in the southern part of Norway.