Overexpression and analysis on posttranslational modification of the retinoic acid related orphan receptor alpha4

The retinoic acid related orphan receptor alpha (RORalpha) regulates the expression of various target genes by binding to specific response elements in their promoter region. RORalpha is an interesting pharmaceutical target since it positively affects several pathophysiological processes of clinical relevance. RORalpha enhances the expression of Apo-AI protein, the major constituent of HDL, which is responsible for the cholesterol transportation. RORalpha notably contributes to the bone mineralization and generation of the extracellular bone matrix, demonstrating its involvement in osteoporosis, and by up-regulating the gene for IKBalpha, RORalpha has anti-inflammatory effects. Moreover, RORalpha is necessary for cerebellar development and the maintenance of the mammalian day-night periodicity governed by the core-clock within the suprachiasmatic nuclei. RORalpha receptors have been reported to bind cholesterol, melatonin, or to function ligand-independent. By monomeric binding to the recognition motif AGGTCA preceded by an A/T-rich sequence (ROR response element, RORE), RORalpha constitutively activates gene transcription. However, RORalpha activity is passively suppressed by its opponents RevErbalpha and RevErbbeta, which both bind to the same target sequence. ...Der Retinoic Acid Related Orphan Recepor alpha (RORalpha) ist ein nukleärer Rezeptor, der die Expression verschiedener Targetgene reguliert, indem er an spezifische Erkennungssequenzen in deren Promotorbereiche bindet. Pharmazeutisches Interesse erweckt RORalpha, weil es einige klinisch relevante pathophysiologische Prozesse positiv beeinflusst. Anti-atherosklerotische Eigenschaften werden RORalpha nachgesagt, da es die Expression von Apo-AI aktiviert, welches den Hauptbestandteil des Cholesterol-transportierenden HDLs darstellt. Durch die Verstärkung der Knochenmineralisierung und dem Aufbau der extrazellulären Knochenmatrix kann RORalpha einer Osteoporose entgegenwirken. Außerdem wirkt RORalpha anti-inflammatorisch, da es die Expression von IKBalpha verstärkt und damit den NF-alphaB-Signalweg hemmt. Des weiteren ist RORalpha an der Gehirnentwicklung und an der Aufrechterhaltung des Tag-Nacht- Rhythmus, der bei Säugetieren in den suprachiasmatischen Nuclei erzeugt wird, beteiligt. Bei Kristallisationsexperimenten wurde Cholesterin in der Ligandenbindungstasche von RORalpha gefunden, und es wird diskutiert, ob auch Melatonin mit dem nukleären Rezeptor interagiert. Allerdings gibt es ebenso Studien die beweisen, dass RORalpha auch ohne Ligand in der aktivierten Konformation vorliegt. Durch monomere Bindung an das DNA-Erkennungsmotiv AGGTCA (ROR response element, RORE), welchem eine A/T-reiche Sequenz vorangeht, kann RORalpha konstitutiv aktivierend wirken. Allerdings kann diese Aktivität durch die Gegenspieler RevErbalpha und RevErbbeta passiv reprimiert werden, da jene die gleichen Motive erkennen und RORalpha aus seiner Bindung verdrängen können. ..

Thermal and Photochemical Generation of Electronically Excited Organic Molecules: Tetramethyl-1,2-dioxetane and Naphthvalene

In this paper some examples of reactions which yield electronically excited products are presented. In particular, the 1,2-dioxetanes are discussed. These molecules cleave cleanly into two carbonyl fragments when heated or irradiated. It will be shown that these simple, high energy, four atom arrays can efficiently generate electronically excited carbonyl fragments when they decompose. Surprisingly, tetramethyl-1,2-dioxetane (V) yields acetone triplet selectively upon thermolysis or photolysis. A study of the kinetics of thermal decomposition of V as a function of solvent, and the mechanistic implications of these observations will be discussed. Based on summation of available evidence, we propose that the thermolyses of 1,2-dioxetanes require specific vibrational motions which enhance spin—orbit coupling as the molecule fragments, and allow efficient decomposition into triplet states. In the photochemistry of V an exceptional 'anti-Stokes' sensitization is demonstrated, which suggests the possibility of efficient execution of 'blue light' photochemistry with 'red light', and a 'quantum chain' reaction. It is demonstrated that, at 77°K, naphthvalene undergoes efficient photochemical conversion to naphthalene triplets. Finally, the relationship of radiationless electronic relaxation and primary photochemical processes is discussed in the framework of our results

Elektronenbeugung in der Gasphase zur Strukturbestimmung von Metallclusterionen

Im Rahmen dieser Arbeit wurden Strukturen von Metallclustern in der Gasphase bestimmt. Dabei wurden Strukturzuordnungen vorgenommen, indem experimentelle Elektronenbeugungsintensitäten (TIED, "Trapped Ion Electron Diffraction") massenselektierter Clusterionen mit simulierten Beugungsintensitäten verschiedener Modellstrukturen aus Dichtefunktionalrechnungen verglichen wurden. Untersuchte Systeme waren v.a. Gold-, Zinn- und Bismutclusterionen mit einer Atomanzahl im Bereich von 11 bis 26

The Hammett correlation between distyrylbenzene substituents and chemiluminescence efficiency providing various ρ-values for peroxyoxalate chemiluminescence of several oxalates

Peroxyoxalate chemiluminescence (PO-CL) was investigated using eight oxalates with various phenol moieties and the distyrylbenzene (DSB) fluorophores with various substituents. The ρ-values in the Hammett correlation between the substituent constants (σp+) of the DSBs and the singlet chemiexcitation yields (ΦS) for the PO-CL reactions varied from −0.50 to −1.01 depending on the oxalate structure, and the reactive oxalates tended to afford the higher absolute ρ-values but with a few exceptions. Based on the CIEEL mechanism, these experimental observations suggest that the aryloxy groups still remain in the 1,2-dioxetanones (DOTs), which are the postulated high-energy intermediates, and control the electronic properties of DOTs as electron-acceptors. The LUMO energies of the DOTs calculated by the ab initio method with a B3LYP/6-31g(d) basis set reveal that the lower the DOT-LUMO energies, the higher the absolute ρ-values were provided for the corresponding oxalates, as predicted by the frontier molecular orbital (FMO) theory. Thus, the chemical species interacting with the DSBs would be not unitary and will be DOTs.ArticleJournal of Photochemistry and Photobiology A: Chemistry. 252:222-231 (2013)journal articl

Excitation and Deexcitation of Benzene

This chapter contains sections titled: - Introduction; - The Nature of the Lower Excited States of Benzene; - Transitions Between Lower Energy States; - Excited State Geometry; - The Influence of the Environment on Electronic States; - The S1 ↔ S0 Radiative Transition; - The S1 ↔ Triplet Radiationless Transition; - The S1 → S0 Radiationless Transition; - The T1 → S0 Phosphorescence Transition; - The T1 → S0 Radiationless Transition; - Transitions from Higher (n > 1) Excited States; - Relevant Photochemical Reactions of Excited States of Benzene; - Benzene Excimer; - Conclusioninfo:eu-repo/semantics/publishedVersio