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Summary: The iron exporter ferroportin (Fpn) is essential to transfer iron from cells to plasma. Systemic iron homeostasis in vertebrates is regulated by the hepcidin-mediated internalization of Fpn. Here, we demonstrate a second route for Fpn internalization; when cytosolic iron levels are low, Fpn is internalized in a hepcidin-independent manner dependent upon the E3 ubiquitin ligase Nedd4-2 and the Nedd4-2 binding protein Nfdip-1. Retention of cell-surface Fpn through reductions in Nedd4-2 results in cell death through depletion of cytosolic iron. Nedd4-2 is also required for internalization of Fpn in the absence of ferroxidase activity as well as for the entry of hepcidin-induced Fpn into the multivesicular body. C. elegans lacks hepcidin genes, and C. elegans Fpn expressed in mammalian cells is not internalized by hepcidin but is internalized in response to iron deprivation in a Nedd4-2-dependent manner, supporting the hypothesis that Nedd4-2-induced internalization of Fpn is evolutionarily conserved. [ABSTRACT FROM AUTHOR]

The embryonic transcription factor Oct-4 is often referred to as the master regulator of the undifferentiated state. Although its role in maintaining embryonic stem (ES) cell pluripotency is well established, its ability to directly reprogram committed somatic cells is not well defined. Using transient transfection, we tested its ability to revert mouse interfollicular epidermal basal keratinocytes to a more ES cell-like state. We found that the Oct-4-transfected keratinocytes expressed the Oct-4 target genes, Sox-2, Nanog, undifferentiated transcription factor 1 (Utf1), and Rex-1. We also noted an increase in developmental potential caused by Oct-4, with the transfected cells able to differentiate into neuronal cells when exposed to neuroectodermal differentiation medium. Control-transfected keratinocytes were unable to respond to the medium, and remained as keratinocytes. These findings suggest that Oct-4 may be the master regulator of the pluripotent state and demonstrate that differentiated somatic cells can be reverted into more developmentally potent cells through the use of a single factor. The latter finding has great implications for therapeutic cell-replacement applications using cells from easily accessible adult tissues, such as the skin.Journal of Investigative Dermatology (2007) 127, 372–380. doi:10.1038/sj.jid.5700531; published online 24 August 2006 [ABSTRACT FROM AUTHOR]

Objective: To identify factors secreted by the human embryo and correlate levels with embryo morphology and pregnancy outcome. Design: A laboratory-based study of human embryo protein synthesis and secretion and a retrospective analysis of spent embryo culture media as it relates to pregnancy outcome. Setting: University-based academic IVF program. Patient(s): IVF patients who had donated cryopreserved human pronuclear-stage embryos. Patients undergoing fresh IVF cycles resulting in a blastocyst transfer who donated spent media drops. Intervention(s): In vitro embryo culture and collection of spent media. Main Outcome Measure(s): Protein analysis and identification by two-dimensional gel electrophoresis and mass spectrometry, ApoA1 quantification by ELISA, and mRNA analysis by quantitative reverse transcriptase–polymerase chain reaction. Result(s): By protein gel electrophoresis, apolipoprotein A1 (ApoA1) was increased in the culture media from good-quality blastocysts (n = 6 embryos) compared to either cleavage-arrested embryos (n = 6 embryos) or poor-quality blastocysts (n = 6 embryos) using spent media from culture days 4 and 5, respectively. Apolipoprotein A1 concentrations were 23.1% greater in day 5 spent culture media from good-grade blastocysts (n = 30) when compared to poor-grade embryos (n = 30). However, in a group of patients (n = 20) with transfer of two good-quality blastocysts, ApoA1 levels from day 5 spent media did not correlate with embryo implantation and pregnancy. Quantitative reverse transcriptase–polymerase chain reaction confirmed the presence of ApoA1 mRNA transcripts in human blastocysts. Conclusion(s): Apolipoprotein A1 is produced by human preimplantation embryos, and increased levels are present in spent culture media containing blastocysts of higher morphologic grade. These results suggest a role for lipoproteins in early embryologic development. [Copyright &y& Elsevier]

Abstract: In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-α and IFN-γ in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium-dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5kDa isoforms of MBP in WT myelin treated with RmAb or IFN-γ. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-γ, or GM-CSF. Neither the 14kDa isoform of MBP nor proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-α and IFN-γ in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and β-tubulin in a sucrose density gradient myelin–axolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-γ. [Copyright &y& Elsevier]