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Background
Minor changes in protein structure induced by small organic and inorganic molecules can result in significant metabolic effects. The effects can be even more profound if the molecular players are chemically active and present in the cell in considerable amounts. The aim of our study was to investigate effects of a nitric oxide donor (spermine NONOate), ATP and sodium/potassium environment on the dynamics of thermal unfolding of human hemoglobin (Hb). The effect of these molecules was examined by means of circular dichroism spectrometry (CD) in the temperature range between 25°C and 70°C. The alpha-helical content of buffered hemoglobin samples (0.1 mg/ml) was estimated via ellipticity change measurements at a heating rate of 1°C/min.
Results
Major results were:
1) spermine NONOate persistently decreased the hemoglobin unfolding temperature T u irrespectively of the Na + /K + environment,
2) ATP instead increased the unfolding temperature by 3°C in both sodium-based and potassium-based buffers and
3) mutual effects of ATP and NO were strongly influenced by particular buffer ionic compositions. Moreover, the presence of potassium facilitated a partial unfolding of alpha-helical structures even at room temperature.
Conclusion
The obtained data might shed more light on molecular mechanisms and biophysics involved in the regulation of protein activity by small solutes in the cell.
The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.
Assessment of RF Safety of Transmit Coils at 7 Tesla by Experimental and Numerical Procedures (490.)
(2012)
Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc–C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate.
N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core.
Entwicklung eines Prototypen zur Prognose von Frühgeburten : ein biomedizintechnischer Ansatz
(2012)
Netzsektoren und deren adäquate Regulierung sind ein sehr relevantes und aktuelles Thema. Dies gilt sowohl für die ökonomische Theorie, die sich sehr intensiv damit auseinandersetzt und in den letzten Jahrzehnten zahlreiche neue Erkenntnisse gewonnen hat. Es gilt ebenso für die Politik, in der Regulierungsfragen kontrovers diskutiert werden und dies nicht nur unter ökonomischen Gesichtspunkten. Es gilt selbstverständlich für die regulierten Unternehmen selbst, deren Tätigkeit durch die staatlichen Regulierungsvorgaben markant beeinflusst wird. Nicht nur die konkreten Inhalte der Regulierungsregime sowie die verbleibenden Freiheitsgrade in der Ausgestaltung sind von Bedeutung, sondern ebenso die Umsetzung durch die Regulierungsbehörden. All dies gilt für den Strommarkt und seinen regulatorischen Hintergrund in besonderer Weise. Die Entflechtung der Stromübertragungsnetze von der Stromproduktion und damit die Vorgaben für die Organisation der Wertschöpfungsketten in den Elektrizitätsunternehmen sind seit dem Beginn des europäischen Liberalisierungsprozesses der Strommärkte ein wichtiges und kontrovers diskutiertes Regulierungselement. Den Fokus bildet das vertikale Unbundling, das letztlich die Diskriminierung von Wettbewerbern durch Anbieter mit aggregierten Wertschöpfungsketten verhindern soll, indem diese gezwungen werden, ihren "Netzteil" anders zu organisieren oder zu verkaufen. Den Mitgliedsstaaten blieben Freiräume in der Ausgestaltung, die in Deutschland erst vor kurzem konkretisiert wurden, und die für die regulierten Unternehmen die Nutzung eines Wahlrechts beinhalten. Der wirtschaftspolitischen folgt nun eine unternehmerische Abwägungsentscheidung.