The Evolutionary Origin of the Runx/CBFbeta Transcription Factors – Studies of the Most Basal Metazoans

BACKGROUND. Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFβ, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. RESULTS. In this study, we detect and characterize the hitherto unexplored Runx/CBFβ genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFβ-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFβ dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFβ are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors. CONCLUSION. These results reveal that Runx and CBFβ likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFβ-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.National Science Foundation (IBN-0212773, FP-91656101-0); Boston University SPRInG (20-202-8103-9); Israel Science Foundation (825/07

Thorium: Uranium fuel cycle in safe reactors, the time is now

The thorium-uranium fuel cycle has several advantages that make it attractive. Some of these beneficial properties are of particular interest now as they help alleviate current concerns. The Th-U cycle has neutronic advantages when utilized in thermal or epithermal reactors. Some of these reactors enjoy extraordinary safety qualities. The combination of these traits suggest that now is an appropriate time to deploy and begin exploiting the Th-U fuel cycle

Operating experience with gas-bearing circulators in a high-pressure helium loop

A high-pressure engineering test loop has been designed and constructed at the Oak Ridge National Laboratory for circulating helium through a test chamber at temperatures to 1000/sup 0/C. The purpose of this loop is to determine the thermal and structural performance of proposed components for the primary loops of gas-cooled nuclear reactors. Five MW of power is available to provide the required gas temperature at the test chamber, and an air-cooled heat exchanger, rated at 4.4 MW, serves as a heat sink. This report contains results of tests performed on gas-bearing circulators

Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin

In skin, multipotent stem cells generate the keratinocytes of the epidermis, sebaceous gland, and hair follicles. In this paper, we show that Tcf3 and Lef1 control these differentiation lineages. In contrast to Lef1, which requires Wnt signaling and stabilized β-catenin to express the hair-specific keratin genes and control hair differentiation, Tcf3 can act independently of its β-catenin interacting domain to suppress features of epidermal terminal differentiation, in which Tcf3 is normally shut off, and promote features of the follicle outer root sheath (ORS) and multipotent stem cells (bulge), the compartments which naturally express Tcf3. These aspects of Tcf3's action are dependent on its DNA binding and Groucho repressor-binding domains. In the absence of its β-catenin interacting domain, Lef1's behavior (ΔNLef1) seems to be markedly distinct from that of ΔNTcf3. ΔNLef1 does not suppress epidermal differentiation and promote ORS/bulge differentiation, but rather suppresses hair differentiation and gives rise to sebocyte differentiation. Taken together, these findings provide powerful evidence that the status of Tcf3/Lef complexes has a key role in controlling cell fate lineages in multipotent skin stem cells