Effects of Copper Exchange Levels on Complexation of Ammonia in Cu (II)-exchanged X Zeolite

Copper (II)-exchanged faujasite-X zeolites at various loadings of copper per unit cell of zeolites were prepared and then exposed to ammonia. The copper ammine complexes of the various copper levels per unit cell were characterized and analyzed by a combination of diffuse reflectance, X-ray powder diffraction, FT-infrared spectroscopy, electron paramagnetic resonance and nuclear magnetic resonance spectroscopic methods. At low copper exchange levels (<5 copper atoms per unit cell), the major complex is [Cu(Ozeo)2(NH3)2]2+ and it is strongly bound to the zeolite framework walls at single four ring sites (site III). Above five copper atoms per unit cell, the major complex becomes [Cu(NH3)4]2+ and it is least interacting with the zeolite framework walls. The [Cu(NH3)4]2+ complex which was formed at higher copper levels per unit cell was most favoured by the presence of maximal amount of ammonia.Keywords: Cation Exchange, Catalysis, Copper, Complexation, Copper AmminesAttached PDF and Supplementary Fil

Towards an Evolutionary Model of Transcription Networks

DNA evolution models made invaluable contributions to comparative genomics, although it seemed formidable to include non-genomic features into these models. In order to build an evolutionary model of transcription networks (TNs), we had to forfeit the substitution model used in DNA evolution and to start from modeling the evolution of the regulatory relationships. We present a quantitative evolutionary model of TNs, subjecting the phylogenetic distance and the evolutionary changes of cis-regulatory sequence, gene expression and network structure to one probabilistic framework. Using the genome sequences and gene expression data from multiple species, this model can predict regulatory relationships between a transcription factor (TF) and its target genes in all species, and thus identify TN re-wiring events. Applying this model to analyze the pre-implantation development of three mammalian species, we identified the conserved and re-wired components of the TNs downstream to a set of TFs including Oct4, Gata3/4/6, cMyc and nMyc. Evolutionary events on the DNA sequence that led to turnover of TF binding sites were identified, including a birth of an Oct4 binding site by a 2nt deletion. In contrast to recent reports of large interspecies differences of TF binding sites and gene expression patterns, the interspecies difference in TF-target relationship is much smaller. The data showed increasing conservation levels from genomic sequences to TF-DNA interaction, gene expression, TN, and finally to morphology, suggesting that evolutionary changes are larger at molecular levels and smaller at functional levels. The data also showed that evolutionarily older TFs are more likely to have conserved target genes, whereas younger TFs tend to have larger re-wiring rates

Identification of Novel Targets of CSL-Dependent Notch Signaling in Hematopoiesis

Somatic activating mutations in the Notch1 receptor result in the overexpression of activated Notch1, which can be tumorigenic. The goal of this study is to understand the molecular mechanisms underlying the phenotypic changes caused by the overexpression of ligand independent Notch 1 by using a tetracycline inducible promoter in an in vitro embryonic stem (ES) cells/OP9 stromal cells coculture system, recapitulating normal hematopoiesis. First, an in silico analysis of the promoters of Notch regulated genes (previously determined by microarray analysis) revealed that the motifs recognized by regulatory proteins known to mediate hematopoiesis were overrepresented. Notch 1 does not bind DNA but instead binds the CSL transcription factor to regulate gene expression. The in silico analysis also showed that there were putative CSL binding sites observed in the promoters of 28 out of 148 genes. A custom ChIP-chip array was used to assess the occupancy of CSL in the promoter regions of the Notch1 regulated genes in vivo and showed that 61 genes were bound by activated Notch responsive CSL. Then, comprehensive mapping of the CSL binding sites genome-wide using ChIP-seq analysis revealed that over 10,000 genes were bound within 10 kb of the TSS (transcription start site). The majority of the targets discovered by ChIP-seq belong to pathways that have been shown by others to crosstalk with Notch signaling. Finally, 83 miRNAs were significantly differentially expressed by greater than 1.5-fold during the course of in vitro hematopoiesis. Thirty one miRNA were up-regulated and fifty two were down-regulated. Overexpression of Notch1 altered this pattern of expression of microRNA: six miRNAs were up-regulated and four were down regulated as a result of activated Notch1 overexpression during the course of hematopoiesis. Time course analysis of hematopoietic development revealed that cells with Notch 1 overexpression mimic miRNA expression of cells in a less mature stage, which is consistent with our previous biological characterization

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Nuclear relaxation of H-2 and H-2@C-60 in organic solvents

none9The 1-H nuclear spin-lattice relaxation time (T-1) of H-2 and H-2@C-60 in organic solvents varies with solvent, and it varies proportionally for H-2 and for H-2@C-60. Since intermolecular magnetic interactions are ruled out, the solvent must influence the modulating processes of the relaxation mechanisms of H-2 both in the solvent cage and inside C-60. The temperature dependence of T-1 also is very similar for H-2 and H-2@C-60, T-1 going through a maximum by varying the temperature in solvents which allow a wide range of temperatures to be explored. This behavior is attributed to the presence of dipolar and spin-rotation mechanisms which have an opposite dependence on temperature.mixedE. SARTORI; M. RUZZI; N. J. TURRO; J. D. DECATUR; D. C. DOETSCHMAN; R. G. LAWLER; A. L. BUCHACHENKO; Y. MURATA; K. KOMATSUE., Sartori; Ruzzi, Marco; N. J., Turro; J. D., Decatur; D. C., Doetschman; R. G., Lawler; A. L., Buchachenko; Y., Murata; K., Komats

Genetically engineered humanized mouse models for preclinical antibody studies.

The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies