A Structural and Mechanistic Study of Two Members of Cupin Family Protein

is a functionally diverse large group of proteins sharing a jelly roll β-barrel fold. An enzymatic member 3-hydroxyanthranilate-3,4-dioxygenase (HAO) and a non-enzymatic member pirin, which is a human nuclear metalloprotein of unknown function present in all human tissues, were selected for structural and functional studies in this dissertation work. HAO is an important enzyme for tryptophan catabolism and for 2-nitrobenzoic acid biodegradation. In this work, seven catalytic intermediate were captured in HAO single crystals, enabling for the first time a nearly complete structural snapshot viewing of the entire molecular oxygen activation and insertion mechanism in an iron- and O2-depedent enzyme. The rapid catalytic turnover rate was found achieved in large part by protein dynamics that facilitates O2 binding to the catalytic iron, which is bound to the enzyme by a facile 2-His-1-carboxylate ligand motif. An iron storage and chaperon mechanism was also discovered in the bacterial source of this enzyme, which led to a proposed novel biological function of a mononuclear iron-sulfur center. Although human pirin protein shares the same structural fold with HAO, its iron ion is coordinated by a 3-His-1-carboxylate ligand motif. Pirin belongs to a subset of proteins whose members are playing regulatory functions in the superfamily. In this work, pirin is shown to act as a redox sensor for the NF-κB transcription factor, a critical mediator of intracellular signaling that has been linked to cellular responses to pro-inflammatory signals which controls the expression of a vast array of genes involved in immune and stress responses

Simulated single molecule microscopy with SMeagol

SMeagol is a software tool to simulate highly realistic microscopy data based on spatial systems biology models, in order to facilitate development, validation, and optimization of advanced analysis methods for live cell single molecule microscopy data. Availability and Implementation: SMeagol runs on Matlab R2014 and later, and uses compiled binaries in C for reaction-diffusion simulations. Documentation, source code, and binaries for recent versions of Mac OS, Windows, and Ubuntu Linux can be downloaded from http://smeagol.sourceforge.net.Comment: v2: 14 pages including supplementary text. Pre-copyedited, author-produced version of an application note published in Bioinformatics following peer review. The version of record, and additional supplementary material is available online at: https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btw10

Essays om det norske sluttbrukermarkedet for elektrisitet

The thesis explores efficiency outcomes following the Norwegian electricity market reform introduced in the early 1990s. Specifically, the thesis investigates efficiency outcomes resulting from the incentive regulation of electricity network companies, the inhererent nature of household consumers and their attitudes to market participation, electricity price development in standard electricity contracts, and the potential for facilitating practices to increase collusive market behavior among retailers. The thesis consists of an extensive introductory chapter that comprises the context and background information to the four empirical studies, data, methods and a summary. Using rich data and sophisticated methods, the thesis brings new evidence to bear on the economics and psychology of household switching behavior of electricity retailers, development in electricity contract prices, and market vehavior among retailers.Denne avhandlingen undersøker og evaluerer reformen innen elektrisitetssektoren som ble innført tidlig på 1990-tallet vurdert fra fire perspektiver: insentivregulering av nettselskap, husholdningskunders aktivitet i sluttbrukermarkedet, prisutviklingen i elektrisitetskontrakter, og markedssvikt som følge av markedsoppførsel som ikke er i tråd med sunn konkurranse. Avhandlingen består av fire artikler samt et introduksjonskapittel som presenterer bakgrunn, data, metode, konklusjon og sammendrag. Artiklene legger til grunn et omfattende datagrunnlag, og benytter avanserte økonometriske metoder for å finne mekanismer og deres empiriske spor som skal besvare spørsmålene som undersøkes. Avhandlingen bidrar til ny innsikt både når det gjelder markedsadferd og prisutvikling.Høgskolen i Østfol

Are There Two Potassium/Argon (K/Ar) Dating Systems?

In textbooks, lectures, and in the mass media, radiometric dates are presented as though they are firmly established scientific procedures not subject to question or debate. Behind the scenes, however, we find quite a different story. As just one example, Skull 1470 has been K/Ar-dated to death, and the effort has been abandoned to use K/Ar to establish its age

Noise-Induced Min Phenotypes in E. coli

The spatiotemporal oscillations of the Escherichia coli proteins MinD and MinE direct cell division to the region between the chromosomes. Several quantitative models of the Min system have been suggested before, but no one of them accounts for the behavior of all documented mutant phenotypes. We analyzed the stochastic reaction-diffusion kinetics of the Min proteins for several E. coli mutants and compared the results to the corresponding deterministic mean-field description. We found that wild-type (wt) and filamentous (ftsZ( −)) cells are well characterized by the mean-field model, but that a stochastic model is necessary to account for several of the characteristics of the spherical (rodA(−)) and phospathedylethanolamide-deficient (PE(−)) phenotypes. For spherical cells, the mean-field model is bistable, and the system can get trapped in a non-oscillatory state. However, when the intrinsic noise is considered, only the experimentally observed oscillatory behavior remains. The stochastic model also reproduces the change in oscillation directions observed in the spherical phenotype and the occasional gliding of the MinD region along the inner membrane. For the PE(−) mutant, the stochastic model explains the appearance of randomly localized and dense MinD clusters as a nucleation phenomenon, in which the stochastic kinetics at low copy number causes local discharges of the high MinD(ATP) to MinD(ADP) potential. We find that a simple five-reaction model of the Min system can explain all documented Min phenotypes, if stochastic kinetics and three-dimensional diffusion are accounted for. Our results emphasize that local copy number fluctuation may result in phenotypic differences although the total number of molecules of the relevant species is high

Can recombinant growth hormone effectively treat idiopathic short stature?

Yes--treatment can increase a child's final height. Injections of recombinant human growth hormone (rGH) at least 3 times a week for 4 to 6 years add 3.7 to 7.5 cm to final height in children between 8 and 16 years of age with idiopathic short stature (strength of recommendation [SOR]: B, 2 small,low-quality, randomized controlled trials [RCTs]). This population comprises children who are otherwise physically and developmentally normal with a height standard deviation score (SDS) of ≤−2.0--comparable to the bottom 2.5% percentile of height--and an adequate response to growth hormone stimulation testing

Thermodynamic Modeling of Variations in the Rate of RNA Chain Elongation of E. coli rrn Operons

AbstractPrevious electron-microscopic imaging has shown high RNA polymerase occupation densities in the 16S and 23S encoding regions and low occupation densities in the noncoding leader, spacer, and trailer regions of the rRNA (rrn) operons in E. coli. This indicates slower transcript elongation within the coding regions and faster elongation within the noncoding regions of the operon. Inactivation of four of the seven rrn operons increases the transcript initiation frequency at the promoters of the three intact operons and reduces the time for RNA polymerase to traverse the operon. We have used the DNA sequence-dependent standard free energy variation of the transcription complex to model the experimentally observed changes in the elongation rate along the rrnB operon. We also model the stimulation of the average transcription rate over the whole operon by increasing rate of transcript initiation. Monte Carlo simulations, taking into account initiation of transcription, translocation, and backward and forward tracking of RNA polymerase, partially reproduce the observed transcript elongation rate variations along the rrn operon and fully account for the increased average rate in response to increased frequency of transcript initiation