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Adult neurogenesis, arising from quiescent radial-glia-like neural stem cells (RGLs), occurs throughout life in the dentate gyrus. How neural stem cells are maintained throughout development to sustain adult mammalian neurogenesis is not well understood. Here, we show that milk fat globule-epidermal growth factor (EGF) 8 (Mfge8), a known phagocytosis factor, is highly enriched in quiescent RGLs in the dentate gyrus. Mfge8-null mice exhibit decreased adult dentate neurogenesis, and furthermore, adult RGL-specific deletion of Mfge8 leads to RGL overactivation and depletion. Similarly, loss of Mfge8 promotes RGL activation in the early postnatal dentate gyrus, resulting in a decreased number of label-retaining RGLs in adulthood. Mechanistically, loss of Mfge8 elevates mTOR1 signaling in RGLs, inhibition of which by rapamycin returns RGLs to quiescence. Together, our study identifies a neural-stem-cell-enriched niche factor that maintains quiescence and prevents developmental exhaustion of neural stem cells to sustain continuous neurogenesis in the adult mammalian brain.

The number of newly formed neurons declines rapidly during aging, and this decrease in neurogenesis is associated with decreased function of neural stem/progenitor cells (NPCs). Here, we determined that a WIP1-dependent pathway regulates NPC differentiation and contributes to the age-associated decline of neurogenesis. Specifically, we found that WIP1 is expressed in NPCs of the m ouse subventricular zone (SVZ) and aged animals with genetically enhanced WIP1 expression exhibited higher NPC numbers and neuronal differentiation compared with aged WT animals. Additionally, augmenting WIP1 expression in aged animals markedly improved neuron formation and rescued a functional defect in fine odor discrimination in aged mice. We identified the WNT signaling pathway inhibitor DKK3 as a key downstream target of WIP1 and found that expression of DKK3 in the SVZ is restricted to NPCs. Using murine reporter strains, we determined that DKK3 inhibits neuroblast formation by suppressing WNT signaling and Dkk3 deletion or pharmacological activation of the WNT pathway improved neuron formation and olfactory function in aged mice. We propose that WIP1 controls DKK3-dependent inhibition of neuronal differentiation during aging and suggest that regulating WIP1 levels could prevent certain aspects of functional decline of the aging brain., Introduction New neurons are generated continuously in 2 distinct regions of the mammalian brain, the subventricular zone (SVZ) and subgranular zone (SGZ). The SVZ represents the largest reserve of neural [...]

Conventional evaluation approaches for complex technologies, such as gas turbine systems, typically use process simulators for modeling, which are usually complicated and time-consuming. In order to facilitate policy analysis, a simplified desktop model for gas turbine systems based upon the air-standard Brayton cycle is developed in Microsoft EXCEL. The simplified model incorporates key process details and includes a comprehensive cost model. The model is calibrated based on a typical 'Frame 7F' heavy duty gas turbine fired with natural gas and syngas. The model generally produces accurate and reasonable estimates for performance and cost comparable to reference data. The model responds appropriately to different syngas compositions, such as based on variation in moisture content and C[O.sub.2] removal. Changes in syngas composition lead to different syngas heating values and thus affect gas turbine performance and cost. The effects of changes in inputs on key outputs are evaluated. Six key inputs are identified that are critical in order to obtain accurate estimates. The simplified model provides detailed technical information in a format that supports strategic planning and analysis. DOI: 10.1061/(ASCE)0733-9402(2007) 133:2(82) CE Database subject headings: Models; Turbines; Simulation; Sensitivity analysis.

Transcription of mammalian LH beta-subunit genes (LHbeta) is regulated by GnRH through activation of early growth response factor-1 (Egr-1), which interacts synergistically with steroidogenic factor-1 (Sf-1) and pituitary homeobox-1 (Pitx1) at the promoter; Egr-1 is thought to comprise the major mediator of this effect. However, the proximal promoters of LHbeta genes in lower vertebrates lack an Egr-1 response element yet are responsive to GnRH; we demonstrate here that the promoter of the Chinook salmon LHbeta (csLHbeta) gene is also unresponsive to Egr-1. The homologous LHbeta promoters in other fish contain a conserved estrogen response element-like sequence, which we recently demonstrated is not required for estrogen receptor (ER) alpha association with the csLHbeta gene. Here we show that the estrogen response element-like element is required for the GnRH effect and for a response to c-jun overexpression. Using plasmid immunoprecipitation, we show that after GnRH exposure, c-jun associates with the intact csLHbeta gene promoter through this element. We further show that the effect of c-jun requires its DNA-binding domain and that c-jun interacts with Sf-1 and ERalpha and exerts synergistic effects on promoter activity with Sf-1, ERalpha, and Pitx1. Finally, we demonstrate the role of c-jun in mediating the GnRH effect on this gene through knockdown of c-jun expression or use of a dominant negative. We conclude that c-jun mediation of the GnRH effect on the LHbeta gene may be common in lower vertebrates and may have preceded an evolutionary divergence in the cis-regulatory elements that led to its function being replaced in mammals by Egr-1.