Summary Oncogene-induced senescence is characterized by a stable cell growth arrest, thus providing a tumor suppression mechanism. However, the underlying mechanisms for this phenomenon remain unknown. Here we show that a decrease in deoxyribonucleotide triphosphates (dNTPs) levels underlies oncogene-induced stable senescence-associated cell growth arrest. The decrease in dNTP levels is caused by oncogene-induced repression of RRM2, the rate-limiting protein in dNTP synthesis. This precedes the senescence-associated cell cycle exit and coincides with the DNA damage response. Consistently, RRM2 downregulation is both necessary and sufficient for senescence. Strikingly, suppression of nucleotide metabolism by RRM2 repression is also necessary for maintenance of the stable senescence-associated cell growth arrest. Further, RRM2 repression correlates with senescence status in benign nevi and melanoma, and its knockdown drives senescence of melanoma cells. These data reveal the molecular basis whereby the stable growth arrest of oncogene-induced senescence is established and maintained through suppression of nucleotide metabolism.

Since the initial inspiration for realizing metal-organic frameworks (MOFs) with zeolitic structures, [1] considerable effort has been made towards novel approaches to construct zeolitic metal-organic frameworks (ZMOFs) by using tetrahedral metal imidazolates. [2][3][4][5][6] To date, numerous ZMOFs have been synthesized with the motifs of which only those with desired porosity and thermal stability are potentially applicable for gas storage, separation, catalysts, encapsulation of target molecules, etc. For rational synthesis of porous and thermostable ZMOFs with the imidazole ligands, the introduction of smaller substituent groups onto imidazole ring has been found to be a vital strategy, [3, 4] because the groups play not only the role of structure-directing agent (template), but also the sites for functionalizing.[4d] Moreover, as an inseparable supporting template, the substituent group can stabilize the imidazolate ZMOFs, however, it also presents an encumbrance that inevitably blocks pores-leading to a reduction of the pore size and surface area.Furthermore, any 2-substituent at the imidazole ring may restrict the flexibility of the M À N bond rotation and render the imidazolates either barely to be generated or lacking in framework diversity. For example, the MOFs of metal 2-sub-II and Co II , Rim = 2-substituent imidazolates) [3, 4a] have been only prepared for those with R-group to be methyl, ethyl, nitro and carboxaldehyde and each of them has been observed with no more than one MOF structure that exhibits the MÀN bond % 2.05 (and M···M distance % 6.0 ). On the supposition that the MÀN bond (and M···M distance) could be expanded (Scheme 1), the lack of framework diversity from a 2-substituent imidazolate might be improved because the elongated M À N bond (and M···M distance) can weaken the selftemplate effect of the 2-substituent group and then, the MÀ N bond is rewarded with a modified flexibility of rotation. Apparently, the synthesis of cadmium 2-substituent imidazolates (CdIFs) of [{CdA C H T U N G T R E N N U N G (R-im) 2 }] 1 (R = methyl, ethyl, n-propyl, n-butyl, phenyl and nitro) shall display the role of a Rgroup and the effect of M À N bond elongation since the already reported cadmium imidazolate framework [7] was observed with a elongated M À N bond % 2.20 (and M···M distance % 6.40 ). In this paper, we report the synthesis, structure and gas adsorption properties of the polymorphous CdIFs.CdIFs of 2-substituent imidazolates were synthesized by solvothermal (or room-temperature) reaction of [Cd-A C H T U N G T R E N N U N G (CH 3 COO) 2 ]·2 H 2 O and 2-substituent imidazoles [R-im-H, R = methyl (mimH), ethyl (eimH), n-propyl (pimH), n-butyl (buimH), phenyl (phimH) and nitro (nimH)] in alkyl-alcohols (or N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA) and 1-methyl-2-pyrollidone (NMP)). Four

A novel lead-free layered perovskite material features both excellent stability and an ideal bandgap of 1.43 eV.

No abstract

Purpose – The purpose of this study was to investigate the pitting resistance and assess the critical pitting temperature (CPT) of a super martensitic stainless steel, 00Cr13Ni5Mo2, made in China, considering especially the difference in the pitting corrosion resistance between the domestic super martensitic stainless steel and an imported one. Design/methodology/approach – Potentiodynamic sweep tests were applied to investigate the effects of four NaCl concentrations (weight per cent) of 1, 3.5, 9 and 17, and four testing temperatures of 30, 50, 75 and 90°C on the pitting resistance of the domestic super martensitic stainless steel in the presence of CO2. Potentiostatic sweep tests were utilized to determine the CPT. Furthermore, chemical immersion exposures, implemented according to the appropriate standard were used to evaluate the difference in the pitting corrosion resistance between the domestic super martensitic stainless steel and an imported one. In addition, the morphology of pits was analyzed using a scanning electron microscope. Finding – The pitting potential of the domestic super martensitic stainless steel decreased with an increase in NaCl concentration and temperature in the presence of CO2. The CPT of the domestic super martensitic stainless steel measured by potentiostatic polarization was 41.16°C. Two types of typical corrosion pits, closed pits formed at 35°C and open pits formed at 50°C, were observed. Furthermore, compared to the super martensitic stainless steel made in Japan, the domestic one was better in terms of pitting potential, corrosion rate and the density of the pits, but worse in terms of the depth of the pits, which may result in a risk of corrosion perforation of tubing and casings. Originality/value – The paper highlights that chloride ions, temperature and the presence of CO2 play an important role on the pitting resistance of super martensitic stainless steel.

Two coordination polymers of cobalt acetate, [Co 5 (O 2 CMe) 10 ] (1) and [Co(O 2 CMe) 2 (H 2 O)]·H 2 O (2), were solvothermally synthesized and characterized by single-crystal and powder Xray diffraction analyses, IR spectroscopy, and elemental analysis. Compound 1 crystallizes in orthorhombic space group Pbcn in two-dimen-

Other natural products U 0800Chemical Constituents from the Fruiting Bodies of the Basidiomycete Albatrellus sp. -The prenylated orcinol derivative, albatrellutin ((R)-I), is isolated along with eight known compounds including three prenylphenols, two pyrazinol derivatives, and three steroids. The compounds are screened for their effect on neurite outgrowth from PC12 cells. -(ZHANG, A.-L.; XU, T.; GAO*, J.-M.; BAI, M.-S.; ZHANG, G.; LIU, H.

Senescence is a cytostatic cell fate that can be induced by oncogene activation, replicative stress or therapy-induced stress. Therapy-induced senescence (TIS) of tumor cells can be initiated by anti-cancer compounds or radiation. TIS is generally considered to be irreversible, and as such this process is believed to be a desirable therapeutic outcome. In this study, we show that melanomas characterized by high levels of the signaling molecule Wnt5A respond to irradiation by undergoing growth arrest, and by expressing classical markers of senescence, including positivity for senescence-associated beta-galactosidase (SA-β-gal), senescence associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. Even though these cells are positive for classical markers of senescence, we find that they retain their ability to migrate and invade. Further, these Wnt5A-high cells are able to proliferate following metastasis and form new tumors in the lung, while expressing increased markers of senescence. Silencing Wnt5A reduces expression of these senescence markers and decreases invasiveness. Finally, Wnt5A-high melanoma cells treated with PLX4720, a BRAFV600E targeted therapy, also increase markers of a TIS response, while remaining invasive. The combined data challenge the paradigm that TIS is a desirable therapeutic endpoint. They also point to Wnt5A as a master regulator of this senescence-like stress-induced phenotype in melanoma. Citation Format: Marie R. Webster, Mai Xu, Kathryn Kinzler, Amanpreet Kaur, Jessica Appleton, Michael P. O'Connell, Katie Marchbank, Alexander Valiga, Vanessa Dang, Michela Perego, Gao Zhang, Ana Slipicevic, Frederick Keeney, Elin Lehrmann, William Wood, III, Kevin Becker, Andrew V. Kossenkov, Meenhard Herlyn, Maureen Murphy, Ashani T. Weeraratna. Wnt5A-expressing melanoma cells show classical markers of senescence following radiation and therapeutic stress, but retain the ability to metastasize and proliferate at distant sites. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B27.