From Regional to National Clouds: TV Coverage in the Czech Republic

Media, and particularly TV media, have a great impact on the general public. In recent years, spatial patterns of information and the relevance of intangible geographies have become increasingly important. Gatekeeping plays a critical role in the selection of information that is transformed into media. Therefore, gatekeeping, through national media, also co-forms the generation of mental maps. In this paper, correspondence analysis (a statistical method) combined with cloud lines (a new visual analytics technique) is used to analyze how individual major regional events in one of the post-communist countries, the Czech Republic, penetrate into the media on a national scale. Although national news should minimize distortions about regions, this assumption has not been verified by our research. Impressions presented by the media of selected regions that were markedly influenced by one or several events in those regions demonstrate that gatekeepers, especially news reporters, functioned as a filter by selecting only a few specific, and in many cases, unusual events for dissemination.     

1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities.

Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF₁ receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF₁ receptor (K_i=9 nM).     

Protein folding pathways of adenylate kinase from E. coli: hydrostatic pressure and stopped-flow studies.

Adenylate kinase (AKe) from E. coli is a small, single-chain, monomeric enzyme with no tryptophan and a single cysteine residue. We have constructed six single-Trp mutants of AKe to facilitate optical studies of these proteins and to specifically examine the interrelationship between their structure, function, dynamics, and folding reactions. In this study, the effects of hydrostatic pressure on the folding reactions of AKe were studied. The native structure of AKe was transformed to a non-native, yet pressure stable, conformation by hydrostatic pressure of about 300 MPa. This pressure lability of AKe is rather low for a monomeric protein and presumably may be attributed to substantial conformational flexibility and a correspondingly large volume change. The refolding of AKe after pressure-induced denaturation was reversible under ambient conditions. At low temperature (near 0 degrees C), the refolding process of pressure-exposed AKe mutants displayed a significant hysteresis. The observation of a slow refolding rate in the 193 region and a faster folding rate around the active site (86, 41, 73 regions) leads us to suggest that in the folding process, priority is afforded to functional regions. The slow structural return of the 193 region apparently does not hinder the more rapid return of enzymatic activity of AKe. Circular dichroism studies on the pressure-denatured Y193W mutant show that the secondary structure (calculated from far-UV spectra) returned at a rapid rate, but the tertiary structure alignment (calculated from near-UV spectra) around the 193 region occurred more slowly at rates comparable to those detected by fluorescence intensity. Denaturation of AKe mutants by guanidine hydrochloride and subsequent refolding experiments were also consistent with a much slower refolding process around the 193 region than near the active site. Fast refolding kinetic traces were observed in F86W, S41W, and A73W mutants using a fluorescence detection stopped-flow rapid mixing device, while only a slow kinetic trace was observed for Y193W. The results suggest that the differences in regional folding rates of AKe are not derived from the specific denaturation methods, but rather are inherent in the structural organization of the protein.     

Higher-Order Homoplasy Tests

The Le Quesne test of character compatibility uses pairwise comparisons of characters to detect homoplasy in phylogenetic character data. If a pair of characters fails this test we can conclude that a minimum of a single extra step is required by the pair of characters. The rationale of the Le Quesne test is extended to comparisons of triplets of characters. The triplet homoplasy test can reveal that that there is a minimum of four extra steps across a triplet of characters and thus that there are at least two extra steps associated with one of the characters. The triplet homoplasy test can thus detect higher orders of homoplasy than can be detected by the pairwise Le Quesne test. The possibility of quartet and other higher-order homoplasy tests is discussed. The utility of higher-order homoplasy tests is discussed. It is suggested higher-order homoplasy tests have potential uses analogous to the uses of the Le Quesne test, particularly with respect to data exploration.     

Identification and functional analysis of NOL7 nuclear and nucleolar localization signals

Background  

NOL7 is a candidate tumor suppressor that localizes to a chromosomal region 6p23. This locus is frequently lost in a number of malignancies, and consistent loss of NOL7 through loss of heterozygosity and decreased mRNA and protein expression has been observed in tumors and cell lines. Reintroduction of NOL7 into cells resulted in significant suppression of in vivo tumor growth and modulation of the angiogenic phenotype. Further, NOL7 was observed to localize to the nucleus and nucleolus of cells. However, the mechanisms regulating its subcellular localization have not been elucidated.