MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma

Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA (siRNA)-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs (miRNAs) in human OS cells compared to mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting miRNA in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, while 3UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3 mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel RUNX2-p53-miR34 network controls cell growth of osseous cells and is compromised in OS.

Marie Sallé, Handel, Rameau and the development of narrative dance music:Bericht vom Internationalen Symposium an der Hochschule fur Musik und Theater Leipzig

Paradigmatic analysis reveals that these two composers developed distinct responses to creating narrative in dance music

Mechanistic Study of 1,3-Butadiene Formation in Acetylene Hydrogenation over the Pd-Based Catalysts Using Density Functional Calculations

Green oil, which leads to the deactivation of the catalysts used for the selective hydrogenation of acetylene, has long been observed but its formation mechanism is not fully understood. In this work, the formation of 1,3-butadiene, known to be the precursor of green oil, on both Pd(111) and Pd(211) surfaces is examined using density functional theory calculations. The pathways containing C-2 + C-2 coupling reactions as well as the corresponding hydrogenation reactions are studied in detail. Three pathways for 1,3-butadiene production, namely coupling plus hydrogenation and further hydrogenation, hydrogenation plus coupling plus hydrogenation, and a two step hydrogenation followed by coupling, are determined. By comparing the effective barriers, we identify the favored pathway on both surfaces. A general understanding toward the deactivation process of the industrial catalysts is also provided. In addition, the effects of the formation of subsurface carbon atoms as well as the Ag alloying on the 1,3-butadiene formation on Pd-based catalysts are also investigated and compared with experimental results.