No abstract

The findings argue against a persistent level of pronounced distress and suggest a classification of the kindling paradigm as a model with moderate severity based on a longer-lasting mild impact on animal behavioral patterns. This suggestion provides a basis for a prospective and retrospective case-by-case severity assessment.

A detailed description of the interaction between Fe(II).bleomycin A2 and the Dickerson-Drew dodecamer d(CGCGAATTCGCG)2 is presented. The reaction between bleomycin and this substrate leads to DNA cleavage at two major sites, adenosine5 and cytidine11, and two minor sites, cytidine3 and thymidine8. The pattern and relative intensities of cleavage at these sites was not entirely consistent with what would be predicted based on the preference of the drug for cleavage at the pyrimidines of 5'-GC-3' and 5'-GT-3' sites. Insight into the origins of the apparent alteration of selectivity was provided by examination of the structure of the duplex which had been determined by X-ray crystallography. This indicated that the C4' hydrogens of the two nucleotides located at the strongest cleavage sites, C11 on one strand and A5 on the other, were oriented toward each other in the minor groove. Two-dimensional NMR measurements and molecular dynamics modeling indicated that a metalloBLM could bind to the duplex in an orientation that positioned the metal center roughly equally close to each of these hydrogen atoms. On the basis of this observation, it was proposed that these two residues represented a double-stranded BLM cleavage site. This hypothesis was tested through the study of the BLM-mediated cleavage of the related decamer duplex, d(CGCGAATTCG).d(CGAATTCGCG), as well as the hairpin sequence d(CGCGAATTCGIIIITTTTCCCCCGAATTCGCG). By the use of the hairpin oligonucleotide 32P-labeled alternately at the 5' and 3'-ends, unequivocal evidence was obtained for BLM-mediated double-strand cleavage. Quantitative analysis of the proportion of damage involving double-strand cleavage was effected by the use of the hairpin substrate; for damage initiated at the predominant cleavage site (cytidine31, analogous to cytidine11 in the dodecanucleotide), it is estimated that 43% of all damage leads to double-stranded lesions. The exceptional efficiency of double-strand cleavage observed in this system must reflect the spatial proximity and orientation of the two sugar H's whose abstraction is required to produce double-stranded lesions.

Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular pathophysiological processes is crucial for the rational selection of innovative biomarkers and target candidates. Here, we subjected proteomic data from different phases of a chronic rat epileptogenesis model to a comprehensive systems level analysis. Weighted Gene Co-expression Network analysis identified several modules of interconnected protein groups reflecting distinct molecular aspects of epileptogenesis in the hippocampus and the parahippocampal cortex. Characterization of these modules did not only further validate the data but also revealed regulation of molecular processes not described previously in the context of epilepsy development. The data sets also provide valuable information about temporal patterns, which should be taken into account for development of preventive strategies in particular when it comes to multi-targeting network pharmacology approaches. In addition, principal component analysis suggests candidate biomarkers, which might inform the design of novel molecular imaging approaches aiming to predict epileptogenesis during different phases or confirm epilepsy manifestation. Further studies are necessary to distinguish between molecular alterations, which correlate with epileptogenesis versus those reflecting a mere consequence of the status epilepticus.

Catalysts containing transition metals like nickel are frequently used in technical hydrogenation reactions. Typically their activity and selectivity are determined via metal dispersion. XRD, H 2 TPD, volumetric chemisorption of H 2 and CO pulse chemisorption were applied to determine the Ni crystallite size of Ni-containing catalysts. The methods were compared with regard to their information content and validity as well as their applicability in quality control during industrial manufacturing of catalysts. Pulse chemisorption of CO showed the best results for utilization in quality control. ProblemNi-containing catalysts are used in various technical hydrogenations such as saturation of aromatics [1 -3], hydrogenation of aldehydes [4,5], hydrogenation of nitroaromatics [6] and hydrogenation of nitriles [7]. The activity and selectivity of these catalysts are mostly determined by the metal dispersion. Therefore, reliable methods for determination of the metal dispersion are required for the development of new catalysts and for quality control of catalysts manufactured in industrial scale. Numerous methods for determining the dispersion of nickel on supports are described in the literature. The most common method is the chemisorption of gases, whereby mainly hydrogen and carbon monoxide are used. The chemisorption can be carried out as a volumetricstatic method [8 -18], as a thermal desorption method [18, 21 -27] or as a pulse-flow method [21, 22, 28 -32] but also gravimetric [33] or calorimetric analyses [34] are applied. Furthermore X-ray diffraction [9 -11, 13 -15, 19, 32, 35, 36], transmission electron microscopy [10 -12, 28] and magnetic methods [37,38] are used for the determination of the Ni dispersion.The aim of this study is to compare different methods with regard to their information content and validity as well as their applicability in quality control during industrial manufacturing of catalysts. These methods are in particular the volumetric-static chemisorption and thermal desorption of H 2 , the pulse chemisorption of CO and the X-ray diffraction on Ni/Al 2 O 3 -, Ni/SiO 2 -and Ni/ZrO 2 /SiO 2 catalysts. Experimental Catalyst PreparationNi/Al 2 O 3 catalysts were prepared by incipient wetness impregnation of extrudated theta-alumina with an aqueous nickel amine carbonate complex solution. After the impregnation the intermediate was dried at 120°C for 12 h and calcined at 330°C for 4 h. For the preparation of Ni/alumina catalyst with Ni content of 17 wt-% a second impregnation of the dried and calcined intermediate has been carried out by using a solution with the same nickel content. The preparation of the catalyst with a Ni content of 24 wt-% was done by carrying out three impregnation steps, while a Ni content of 28 wt-% was reached with four impregnation steps. After the calcination 200 mL of the catalyst precursor were heated up with a rate of 5°C min -1 to 450°C by using H 2 (space velocity of 2000 L gas L cat -1 h -1) followed by a 6-h hold at 450°C. After cooling down to ambient temperat...