ABSTRACT
We describe an entirely new type of tetrahedral cluster, representing a new level of structural hierarchy: a hybrid tetrahedron of supertetrahedra, formed by five T3 supertetrahedral clusters connected by bipyridyl linkers. Covalent assembly of these 37 Å super-supertetrahedra with smaller (10 Å) T3 clusters results in the formation of a two-dimensional covalent network which contains pores in the mesoporous range.
ABSTRACT
The synthesis and characterization of five new indium selenides, [C9H17N2]3[In5Se(8+x)(Se2)(1-x)] (1-2), [C6H12N2]4[C6H14N2]3[In10Se15(Se2)3] (3), [C6H14N2][(C6H12N2)2NaIn5Se9] (4) and [enH2][NH4][In7Se12] (5), are described. These materials were prepared under solvothermal conditions, using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO) as structure-directing agents. Compounds 1-4 represent the first examples of ribbons in indium selenides, and 4 is the first example of incorporation of an alkali metal complex. Compounds 1, 2 and 4 contain closely related [In5Se(8+x)(Se2)(1-x)](3-) ribbons which differ only in their content of (Se2)(2-) anions. These ribbons are interspaced by organic countercations in 1 and 2, while in 4 they are linked by highly unusual [Na(DABCO)2](+) units into a three-dimensional framework. Compound 3 contains complex ribbons, with a long repeating sequence of ca. 36 Å, and 4 is a non-centrosymmetric three-dimensional framework, formed as a consequence of the decomposition of DABCO into ethylenediamine (en) and ammonia.
ABSTRACT
CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19(Arf) and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf) promoter reporter. To determine whether p19(Arf) is responsible for the proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19(Arf) is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents.
Subject(s)
CCAAT-Enhancer-Binding Protein-beta/metabolism , DNA Damage , Repressor Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis/drug effects , CCAAT-Enhancer-Binding Protein-beta/deficiency , Carcinogens/toxicity , Cell Survival/drug effects , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclophosphamide/administration & dosage , Cyclophosphamide/pharmacology , Epidermal Cells , Epidermis/drug effects , Epidermis/metabolism , Injections, Intraperitoneal , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/metabolism , Mice , Oncogene Protein p21(ras)/metabolism , Protein Processing, Post-Translational/drug effects , Transcriptional Activation/drug effects , Tumor Suppressor Protein p53/geneticsABSTRACT
Recent studies have identified roles for C/EBPbeta in cellular survival and tumorigenesis, however, the mechanisms through which C/EBPbeta regulates these processes are not fully understood. Previously, we demonstrated that C/EBPbeta(-/-) mice are resistant to carcinogen-induced skin tumorigenesis and in response to topical carcinogen treatment display a 17-fold increase in keratinocyte apoptosis compared to wild-type mice. Here, we have investigated the mechanisms through which C/EBPbeta regulates apoptosis in response to carcinogenic stress. Analysis of carcinogen-treated C/EBPbeta(-/-) mouse skin revealed a striking increase in the number of p53 immunopositive keratinocytes in the epidermis of C/EBPbeta(-/-) mice compared to wild-type mice and this increase was temporally associated with a concomitant anomalous increase in apoptosis. The increased levels of p53 were functional as Mdm2, Bcl-2, C/EBPalpha and p21 were differentially regulated in the epidermis of carcinogen-treated C/EBPbeta(-/-) mice. The increase in p53 protein was not associated with an increase in p53 mRNA levels. To determine whether p53 is required for the increased apoptosis in C/EBPbeta(-/-) mice, C/EBPbeta/p53 compound knockout mice were generated. Carcinogen-treated C/EBPbeta/p53 compound knockout mice did not display increased apoptosis demonstrating p53 is required for the proapoptotic phenotype in C/EBPbeta(-/-) mice. Our results demonstrate that altered keratinocyte survival in C/EBPbeta(-/-) mice results from aberrant regulation of p53 protein and function and indicate C/EBPbeta has a role in the negative regulation of p53 protein levels in response to carcinogen-induced stress.
Subject(s)
Apoptosis , CCAAT-Enhancer-Binding Protein-beta/physiology , Epidermis/pathology , Gene Expression Regulation, Neoplastic , Keratinocytes/pathology , Tumor Suppressor Protein p53/metabolism , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Animals , CCAAT-Enhancer-Binding Protein-beta/genetics , Carcinogens/toxicity , Cell Survival , Epidermis/drug effects , Epidermis/metabolism , Female , Immunoenzyme Techniques , In Situ Nick-End Labeling , Keratinocytes/drug effects , Keratinocytes/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53/geneticsABSTRACT
Although standard administration procedures are essential for valid inference making, current Profile and Mood States (POMS; McNair, Lorr, & Droppleman, 1971) protocol forces each examiner, when asked for assistance, to provide subjects extemporaneously with a word or phase that is: (a) synonymous with the original item, (b) located nowhere else on the instrument, and (c) more meaningful to the subject than the original item. The purpose of this article is to describe an empirically based extension of current POMS protocol designed to augment uniformity in administration procedures by providing examiners with a standardized list of alternatives to be referred to when questions concerning the meaning of POMS items arise. A multiphase survey procedure was employed to generate and refine alternative items. A series of alpha (internal consistency) reliabilities, calculated for the POMS subscales after each alternative was substituted, revealed little change in subscale homogeneity resulting from the substitution of the alternatives.
