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941.
942.
943.
Karasawa A Erkens GB Berntsson RP Otten R Schuurman-Wolters GK Mulder FA Poolman B 《The Journal of biological chemistry》2011,286(43):37280-37291
The cystathionine β-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are critical for transport activity and/or ionic regulation of transport, whereas CBS1 serves no functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide-binding domain are more accessible for cross-linking at high than low ionic strength, indicating that these domains undergo conformational changes when transiting between the active and inactive state. Structural analyses suggest that the cystathionine β-synthase module is largely unstructured. Moreover, we could substitute CBS1 by a linker and preserve ionic regulation of transport. These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2 interface forms a hinge point for ionic strength-dependent rearrangements that are transmitted to the nucleotide-binding domain and thereby affect translocation activity. 相似文献
944.
Kalita MK Sargsyan K Tian B Paulucci-Holthauzen A Najm HN Debusschere BJ Brasier AR 《The Journal of biological chemistry》2011,286(43):37741-37757
The canonical nuclear factor-κB (NF-κB) signaling pathway controls a gene network important in the cellular inflammatory response. Upon activation, NF-κB/RelA is released from cytoplasmic inhibitors, from where it translocates into the nucleus, subsequently activating negative feedback loops producing either monophasic or damped oscillatory nucleo-cytoplasmic dynamics. Although the population behavior of the NF-κB pathway has been extensively modeled, the sources of cell-to-cell variability are not well understood. We describe an integrated experimental-computational analysis of NF-κB/RelA translocation in a validated cell model exhibiting monophasic dynamics. Quantitative measures of cellular geometry and total cytoplasmic concentration and translocated RelA amounts were used as priors in Bayesian inference to estimate biophysically realistic parameter values based on dynamic live cell imaging studies of enhanced GFP-tagged RelA in stable transfectants. Bayesian inference was performed on multiple cells simultaneously, assuming identical reaction rate parameters, whereas cellular geometry and initial and total NF-κB concentration-related parameters were cell-specific. A subpopulation of cells exhibiting distinct kinetic profiles was identified that corresponded to differences in the IκBα translation rate. We conclude that cellular geometry, initial and total NF-κB concentration, IκBα translation, and IκBα degradation rates account for distinct cell-to-cell differences in canonical NF-κB translocation dynamics. 相似文献
945.
946.
Information on the structural characteristics and inhibitory activity of the pacifastin family is restricted to a handful of locust pacifastin-related inhibitors. In this report the optimization of a bacterial recombinant expression system is described, resulting in the high yield production of pacifastin-like inhibitors of the desert locust. Subsequently, the relative inhibitory activity of these peptides towards mammalian, locust and caterpillar digestive peptidases has been compared. In general, the enzyme specificity of locust pacifastin-like inhibitors towards trypsin- or chymotrypsin-like peptidases corresponds to the nature of the P1-residue at the reactive site. In addition, other structural characteristics, including specific core interactions, have been reported to result in a different affinity of pacifastin members towards digestive trypsin-like enzymes from mammals and arthropods. One remarkable observation in this study is a specifically designed pacifastin-like peptidase inhibitor, which, unlike other inhibitors of the same family, does not display this specificity and selectivity towards digestive enzymes from different animals. 相似文献
947.
Bert U Kleine Johannes P van Dijk Bernd G Lapatki Machiel J Zwarts Dick F Stegeman 《Journal of electromyography and kinesiology》2007,17(5):535-548
Recently, high-density surface EMG electrode grids and multi-channel amplifiers became available for non-invasive recording of human motor units (MUs). We present a way to decompose surface EMG signals into MU firing patterns, whereby we concentrate on the importance of two-dimensional spatial differences between the MU action potentials (MUAPs). Our method is exemplified with high-density EMG data from the vastus lateralis muscle of a single subject. Bipolar and Laplacian spatial filtering was applied to the monopolar raw signals. From the single recording in this subject six different simultaneously active MUs could be distinguished using the spatial differences between MUAPs in the direction perpendicular to the muscle fiber direction. After spike-triggered averaging, 125-channel two-dimensional MUAP templates were obtained. Template-matching allowed tracking of all MU firings. The impact of spatial information was measured by using subsets of the MUAP templates, either in parallel or perpendicular to the muscle fiber direction. The use of one-dimensional spatial information perpendicular to the muscle fiber direction was superior to the use of a linear array electrode in the longitudinal direction. However, to detect the firing events of the MUs with a high accuracy, as needed for instance for estimation of firing synchrony, two-dimensional information from the complete grid electrode appears essential. 相似文献
948.
949.
Theresa M. Bert Richard G. Harrison 《Evolution; international journal of organic evolution》1988,42(3):528-544
Two distinct taxa of marine crabs (Menippe mercenaria and M. adina, sensu Williams and Felder [1986]) interbreed extensively in two disjunct areas of the coastal southeastern United States. We used variation in coloration and allele frequencies at three diagnostic loci to examine in detail the structure of the two zones of variation. A narrow hybrid zone in northwest Florida is situated at the junction of the present ranges of the two parental forms, in an area of strong ecological change and hydrological convergence. Despite extensive hybridization in this area, there is a significant deficiency of heterozygotes for the Alp-2 locus, nonrandom associations of alleles for two diagnostic loci, and an absence of certain combinations of phenotypes and genotypes. Along the Atlantic coast (east central Florida into South Carolina), a broad zone of increased variability exists within the range of M. mercenaria. Allele frequencies throughout this zone are similar to those of M. mercenaria but reflect apparent introgression from M. adina. In contrast, color patterns are quite variable, but only in the center of this zone. There is little evidence of a heterozygote deficiency, and the preferred habitat of M. mercenaria is not present. The Atlantic zone of variability is apparently expanding, with alleles at enzyme loci introgressing more rapidly than color characteristics. Despite these differences, certain features are common to both zones. These include 1) asymmetry in terms of the direction of introgression, 2) differential introgression of alleles, and 3) an almost complete absence of M. adina phenotypes that carry high proportions of M. mercenaria alleles. Differences between the two zones illustrate the influence that environmental setting, time of contact in relation to time of divergence, and location of the zone relative to the parental species ranges can have on hybridization events. However, observed similarities between the zones suggest that certain patterns of introgression and recombination may be independent of environmental setting. Thus, we suggest that factors inherent to the organism (intrinsic factors) and factors inherent to the environment (extrinsic factors) both act to structure and maintain the two hybrid zones. 相似文献
950.
Bert Rutten Claudia Tersteeg Joyce E. P. Vrijenhoek Thijs C. van Holten Ellen H. A. M. Elsenberg Elske M. Mak-Nienhuis Gert Jan de Borst J. Wouter Jukema Nico H. J. Pijls Johannes Waltenberger Anton Jan van Zonneveld Frans L. Moll Elizabeth McClellan Andrew Stubbs Gerard Pasterkamp Imo Hoefer Philip G. de Groot Mark Roest 《PloS one》2014,9(8)