(Am J Pathol 2008, 173:1747-1757; DOI: 10.2353/ajpath.2008.080527)”
“Osteoprotegerin (OPG), a member of the TNF receptor superfamily, was initially found to modulate bone mass by blocking osteoclast maturation and function. Rodent Dihydrotestosterone molecular weight models have also revealed a role for OPG as an inhibitor of vascular calcification. However, the precise mode of how OPG blocks mineralization is unclear. In this study, OPG was

found in an in vitro assay to significantly inhibit calcification of vascular smooth muscle cells (VSMC) induced by high calcium/phosphate (Ca/P) treatment (p = 0.0063), although this effect was blunted at high OPG concentrations. By confocal microscopy, OPG was detected in VSMC in the Golgi, the same localization seen in osteoblasts, which express

OPG in bone. Treatment of VSMC by minerals (Ca, P. or both) induced OPG mRNA expression as assessed by real-time quantitative PCR, and VSMC derived from atherosclerotic plaque material also exhibited higher OPG expression as compared to control cells (p < 0.05). Furthermore, OPG was detected by Western compound inhibitor blotting in matrix vesicles (MV), nanoparticles that are released by VSMC with the capacity to nucleate mineral. In atherosclerotic arteries, OPG colocalized immunohistochemically with annexin VI, a calcium-dependent membrane and phospholipid binding protein found in MV. Thus, the calcification inhibitor OPG is contained in crystallizing MV and has a biphasic effect on VSMC: physiologic concentrations inhibit calcification, whereas high concentrations commonly seen in patients with vascular disease have no effect. Like other calcification inhibitors, OPG may be specifically loaded into these nanoparticles to be deposited at remote sites, where it acts to inhibit calcification. (C) 2011 Elsevier Inc. All rights reserved.”
“The myb-DNA binding domain is characterized by a 3-alpha helical bundle and three repeats of this domain drive sequence specific DNA binding of the c-myb transcription factor. Human TRF1 contains a single myb-related domain and as a homodimer, enables the sequence

specific binding of telomeric DNA. In this report we provide a kinetic assessment of hTRF1 DNA binding activity. Using intrinsic fluorescence quenching we present evidence that hTRF1 binds to both telomeric and non-telomeric DNA check details with kinetic discrimination to allow stable binding to telomeric tracts of DNA. The position of telomere repeats does not impact binding though the number of repeats and structure does impact binding. Kinetic analysis of DNA-dependent intrinsic tryptophan fluorescence quenching of hTRF1 revealed a two step binding process that is impacted by telomere repeat length, position, and structure. These data are consistent with existing structural and equilibrium binding data for hTRF1 recognition and binding of telomere DNA. (C) 2009 Elsevier Inc. All rights reserved.”
“Neoadjuvant chemotherapy is widely used to downstage breast cancers before surgery.