No abstract

We have obtained 3 microns spectra at several positions in the Orion Bar region and in the "Red Rectangle," the nebula surrounding HD 44179. The recently discovered weak emission features at 3.40, 3.46, 3.51, and 3.57 microns (2940, 2890, 2850, and 2800 cm-1) are prominent in the Orion Bar region. The 3.40 microns and 3.51 microns features increases in intensity relative to the dominant 3.29 microns (3040 cm-1) feature when going from the ionized to the neutral zone across the Orion Bar. However, only a weak and rather broad 3.40 microns feature is present at the position of HD 44179. These spectra demonstrate that some of the 3 microns emission components vary independently of each other and in a systematic way within UV-excited nebulae. This spatial variation is discussed in terms of the UV excitation and photochemical evolution of polycyclic aromatic hydrocarbons and related molecular structures. The spatial behavior of the weak emission features can be understood qualitatively in terms of hot bands of the CH stretch and overtones and combination bands of other fundamental vibrations in simple PAHs. An explanation in terms of emission by molecular sidegroups attached to the PAHs is less straightforward, particularly in the case of the Red Rectangle and other evolved mass-losing objects. We estimate PAH sizes of 20-50 carbon atoms based on the susceptibility of PAHs to destruction by the far ultraviolet fields present in the Orion Bar and the Red Rectangle; the size range is similar to independent estimates made previously.

No abstract

The mammalian cell nucleus contains a variety of organelles or nuclear bodies which contribute to key nuclear functions. Promyelocytic leukemia nuclear bodies (PML NBs) are involved in the regulation of apoptosis, antiviral responses, the DNA damage response and chromatin structure, but their precise biochemical function in these nuclear pathways is unknown. One strategy to tackle this problem is to assess the biophysical properties of the component parts of these macromolecular assemblies in living cells. In this study we determined PML NB assembly dynamics by live cell imaging, combined with mathematical modeling. For the first time, dynamics of PML body formation were measured in cells lacking endogenous PML. We show that all six human nuclear PML isoforms are able to form nuclear bodies in PML negative cells. All isoforms exhibit individual exchange rates at NBs in PML positive cells but PML I, II, III and IV are static at nuclear bodies in PML negative cells, suggesting that these isoforms require additional protein partners for efficient exchange. PML V turns over at PML Nbs very slowly supporting the idea of a structural function for this isoform. We also demonstrate that SUMOylation of PML at Lysine positions K160 and/or K490 are required for nuclear body formation in vivo.We propose a model in which the isoform specific residence times of PML provide both, structural stability to function as a scaffold and flexibility to attract specific nuclear proteins for efficient biochemical reactions at the surface of nuclear bodies.MCS code: 92C37

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.