University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

Energy decomposition analysis

Abstract: The energy decomposition analysis (EDA) is a powerful method for a quantitative interpretation of chemical bonds in terms of three major components. The instantaneous interaction energy ΔEint between two fragments A and B in a molecule A–B is partitioned in three terms, namely (1) the quasiclassical electrostatic interaction ΔEelstat between the fragments; (2) the repulsive exchange (Pauli) interaction ΔEPauli between electrons of the two fragments having the same spin, and (3) the orbital (covalent) interaction ΔEorb which comes from the orbital relaxation and the orbital mixing between the fragments. The latter term can be decomposed into contributions of orbitals with different symmetry which makes it possible to distinguish between σ, π, and δ bonding. After a short introduction into the theoretical background of the EDA we present illustrative examples of main group and transition metal chemistry. The results show that the EDA terms can be interpreted in chemically meaningful way thus providing a bridge between quantum chemical calculations and heuristic bonding models of traditional chemistry. The extension to the EDA–Natural Orbitals for Chemical Valence (NOCV) method makes it possible to breakdown the orbital term ΔEorb into pairwise orbital contributions of the interacting fragments. The method provides a bridge between MO correlations diagrams and pairwise orbital interactions, which have been shown in the past to correlate with the structures and reactivities of molecules. There is a link between frontier orbital theory and orbital symmetry rules and the quantitative charge- and energy partitioning scheme that is provided by the EDA–NOCV terms. The strength of the pairwise orbital interactions can quantitatively be estimated and the associated change in the electronic structure can be visualized by plotting the deformation densities. For further resources related to this article, please visit the WIREs website.

Cutting Edge: Preferentially the R-Stereoisomer of the Mycoplasmal Lipopeptide Macrophage-Activating Lipopeptide-2 Activates Immune Cells Through a Toll-Like Receptor 2- and MyD88-Dependent Signaling Pathway

Abstract: Mycoplasmas and their membranes are potent activators of macrophages, the active principle being lipoproteins and lipopeptides. Two stereoisomers of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 (MALP-2) differing in the configuration of the lipid moiety were synthesized and compared in their macrophage-activating potential, the R-MALP being >100 times more active than the S-MALP in stimulating the release of cytokines, chemokines, and NO. To assess the role of the Toll-like receptor (TLR) family in mycoplasmal lipopeptide signaling, the MALP-2-mediated responses were analyzed using macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice. TLR2- and MyD88-deficient cells showed severely impaired cytokine productions in response to R- and S-MALP. The MALP-induced activation of intracellular signaling molecules was fully dependent on both TLR2 and MyD88. There was a strong preference for the R-MALP in the recognition by its functional receptor, TLR2.

Lisinopril-Mediated Regression of Myocardial Fibrosis in Patients With Hypertensive Heart Disease

Abstract: Background—In arterial hypertension, left ventricular hypertrophy (LVH) includes myocyte hypertrophy and fibrosis, which leads to LV diastolic dysfunction and, finally, heart failure. In spontaneously hypertensive rats, myocardial fibrosis was regressed and LV diastolic function was improved by treatment with the angiotensin-converting enzyme inhibitor lisinopril. Whether this holds true for patients with hypertensive heart disease was addressed in this prospective, randomized, double-blind trial. Methods and Results—A total of 35 patients with primary hypertension, LVH, and LV diastolic dysfunction were treated with either lisinopril (n=18) or hydrochlorothiazide (HCTZ; n=17). At baseline and after 6 months, LV catheterization with endomyocardial biopsy, Doppler echocardiography with measurements of LV peak flow velocities during early filling and atrial contraction and isovolumic relaxation time, and 24-hour blood pressure monitoring were performed. Myocardial fibrosis was measured by LV collagen volume...

Steroid hormone receptors: an update

Abstract: Steroid hormones (SHs) are lipophilic molecules derived from cholesterol and synthesized in the adrenal cortex (glucocorticoids, mineralocorticoids, and adrenal androgens), the testes (testicular androgens, oestrogen), and the ovary and placenta (oestrogens and progestagens or progestins). SHs reach their target cells via the blood, where they are bound to carrier proteins, and because of their lipophilic nature pass the cell membrane by simple diffusion. Within the target cells SHs bind to steroid hormone receptors (SHRs), the key mediators of SH action, which are complexed to chaperones, e.g. heat shock protein 90 (Hsp90), that help other proteins to fold and prevent aggregation. SHRs are intracellular transcription factors that can be activated, among other possibilities, by the specific and high affinity binding of ligand to exert positive or negative effects on the expression of target genes. Binding of agonistic or antagonistic ligands leads to different allosteric changes of SHRs making them competent to exert positive or negative effects on the expression of target genes by different mechanisms. (i) After dissociation of chaperones the liganded SHR-complexes can bind to chromatin organized DNA sequences in the vicinity of target genes, termed hormone response elements (HREs). The HRE-recruited hormone-receptor-complexes are then able to initiate chromatin remodelling and to relay activating or repressing signals to the target genes transcription machinery; (ii) through protein-protein interactions with other sequence-specific transcription factors, SHRs can also regulate the activity of many genes that are switched on, for instance, during stress or an inflammatory response; (iii) the SH response can also be integrated in the intracellular signalling network via cross-talk of SHRs with signal transduction pathways that transmit extracellular signals via membrane receptors and activation of protein kinase cascades to nuclear transcription factors that activate various target genes. By all these different mechanisms SHRs modulate numerous and specific responses in a large variety of cells, whereby their particular effect depends on the physiological, cellular and genetic context.