Dispersion relations and speeds of sound in special sectors for the integrable chain with alternating spins

Based on our previous analysis \cite{doerfel3} of the anisotropic integrable chain consisting of spins $s=1/2$ and $s=1$ we compare the dispersion relations for the sectors with infinite Fermi zones. Further we calculate the speeds of sound for regions close to sector borders, where the Fermi radii either vanish or diverge, and compare the results.Comment: 11 pages, LaTeX2e, uses iopart.cls,graphicx.sty and psfrag.sty, 2 figure

Complete phase diagram for the integrable chain with alternating spins in the sectors with competing interactions

We investigate the anisotropic integrable spin chain consisting of spins $s={1/2}$ and $s=1$ by means of thermodynamic Bethe ansatz for the anisotropy $\gamma>\pi/3$, where the analysis of the Takahashi conditions leads to a more complicated string picture. We give the phase diagram with respect to the two real coupling constants $\bar{c}$ and $\tilde{c}$, which contains a new region where the ground state is formed by strings with infinite Fermi zones. In this region the velocities of sound for the two physical excitations have been calculated from the dressed energies. This leads to an additional line of conformal invariance not known before.Comment: 13 pages, LaTeX, uses ioplppt.sty and epsfig.sty, figure 3 correcte

High Molecular Weight Kininogen-a novel factor in the regulation of apoptosis of vascular smooth muscle cells

Titelblatt, Danksagung, Inhaltsverzeichnis 1\. Einleitung 2\. Material und Methoden 3\. Ergebnisse 4. Diskussion 5\. Zusammenfassung 6\. Abstract 7\. Literaturverzeichnis 8\. Abbildungs- und Tabellenverzeichnis 9\. Curriculum vitae VeröffentlichungenDie Funktion von HMWK als Cystein-Proteasen-Inhibitor ist schon seit längerem bekannt, jedoch wurden Interaktionen im Gewebe- bzw. Zellsystem als auch die Involvierung in pathophysiologische Vorgänge bisher nicht untersucht. Die Apoptose von VSMC nimmt eine zentrale Stellung in der Pathogenese von vaskulären Pathologien, wie z.B. des AAA ein. In der vorliegenden Arbeit wurde untersucht, ob HMWK eine inhibitorische Wirkung auf Cystein-Proteasen in VSMC ausübt und dies somit zu einer verringerten Aktivität der Cystein-Proteasen und Inhibierung der Apoptose in VSMC führt. In der vorliegenden Arbeit wurde gezeigt, dass HMWK konzentrationsabhängig die Apoptose, gemessen über die Aktivierung von Caspase-3 als auch die Gesamtapoptoserate, gleichermaßen in VSMC von BN und BN/Ka beeinflusste. Es erfolgte in dem verwendeten Apoptoseinduktions-Modell sowohl eine Inhibierung der extrinsischen apoptotischen Kaskade als auch der intrinsischen apoptotischen Kaskade durch HMWK durch eine Hemmung der Aktivierung der jeweiligen Initiator-Caspasen und der Freisetzung von lysosomalen und mitochondriellen Proteinen. Darüberhinaus stimulierte HMWK, abgesehen von der Cystein-Proteasen-inhibitorischen Eigenschaft, zugleich anti-apoptotische Mechanismen, wie Bcl-XL und phospho-42/44 MAPK. Die beobachteten Effekte waren unabhängig von Bradykinin. Der Vergleich von BN und den defizienten BN/Ka zeigte für letztere erhöhte basalen mRNA-Expressionslevel für apoptotischen Proteine sowie reduzierte Level für das anti-apoptotische Proteine. Expressionsuntersuchungen ergaben keine HMWK mRNA Produktion in VSMC. In einem Rettungs-Experiment konnte gezeigt werden, dass ebenfalls durch endogene HMWK-Produktion die Apoptoserate gesenkt wird. Verschiedene Aufnahmestudien mit fluoreszenzmarkiertem HMWK ergaben eine zeitabhängige und irreversible Aufnahme von HMWK in das Zytosol von VSMC, die nicht durch einen Endozytose-Inhibitor blockierbar war. Zudem wurde eine hohe Kolokalisation von HMWK mit aktiven apoptotischen Proteasen festgestellt und somit ein erster mechanistischer Ansatz für die inhibitorische Wirkung von HMWK auf Cystein-Proteasen aufgezeigt. Daraus ergeben sich fortführende Hypothesen, in denen sowohl die spezifischen inhibitorischen Eigenschaften der einzelnen HMWK-Domänen und der zelluläre Aufnahmemechanismus durch VSMC als auch die Übertragung der gefundenen Ergebnisse auf das BN/Ka-Versuchsmodell weiter zu definieren sind. Desweiteren bieten erste pharmakologisch-interventive Ansätze, mit z.B. ACE-Hemmern, AT1 -Rezeptor-Blockern, Fibraten und Tetracyclinen, die Möglichkeit der Untersuchung der Beeinflussung des pathologischen HMWK-Mangels.Objective. Apoptosis of VSMC is considered as a crucial event in the pathogenesis of vascular diseases like aneurysms. In this study, we tested the hypothesis that high-molecular-weight kininogen is directly involved in cellular pathways by preventing apoptosis of VSMC. Methods and results. In VSMC derived from BN/Ka, a rat strain which is plasma-deficient in HMWK due to a mutation of the kininogen gene, basal mRNA levels of apoptotic proteins were elevated and of the anti-apoptotic Bcl-XL were decreased compared to BN rats. HMWK concentration-dependently prevented aortic VSMC from entering apoptosis which was associated with a down-regulation of apoptotic index, cleaved caspase 3 and 9, decreased caspase 8 activity and reduced release of cytochrome C and cathepsin B into the cytosol. Consistent with these results, the expression of the anti-apoptotic protein Bcl-XL and phospho-42/44 MAPK was increased by HMWK. These findings were confirmed by rescue of VSMC transfected with an HMWK expression vector. All observed effects of HMWK were independent of bradykinin. No endogeneous HMWK mRNA production was detectable in VSMC. Furthermore, VSMC were able to bind and internalize irreversibly HMWK, which colocalized with active apoptotic proteases. Conclusion. Our findings, demonstrating for the first time multiple direct anti-apoptotic effects of HMWK in VSMC, point to a cellular mechanism by which HMWK rescues VSMC from apoptosis

Functional Investigations into the Recognition Memory Network, its Association with Genetic Polymorphisms and Implications for Disorders of Emotional Memory

Recent research, that has been focused on recognition memory, has revealed that two processes contribute to recognition of previously encountered items: recollection and familiarity (Aggleton & Brown, 1999; Eichenbaum, 2006; Eichenbaum, Yonelinas, & Ranganath, 2007; Rugg & Yonelinas, 2003; Skinner & Fernandes, 2007; Squire, Stark, & Clark, 2004; Wixted, 2007a; Yonelinas, 2001a; Yonelinas, 2002). The findings of neural correlates of recollection and familiarity lead to the assumption that there are different brain regions activated in either process, but there are, to the best of my knowledge, no studies assessing how these brain regions are working together in a recollection or a familiarity network, respectively. Additionally, there are almost no studies to date, which directly searched for overlapping regions. Therefore, in study I of the current thesis, brain regions associated to both recognition processes are searched investigated. Additionally, a connectivity analysis will search for functional correlated brain activations that either build a recollection or a familiarity network. It is undoubtable that the Brain Derived Neurotrophic Factor (BDNF) is strongly involved in synaptic plasticity in the hippocampus (Bramham & Messaoudi, 2005) and there is evidence that a genetic variant of this neurotrophin (BDNF 66Met) is related to poorer memory performance (Egan, et al., 2003). Therefore, in study II of the current thesis, the effect of BDNF Val66Met on recollection and familiarity performance and related brain activations is investigated. Finally, one could summarize, that serotonin, like BDNF, is strongly involved in brain development and plasticity as well as in learning and memory processes (Vizi, 2008). More precisely, there is evidence for alterations in the structure of brain regions, which are known to be involved in emotional memory formation and retrieval, like amygdala and hippocampus (Frodl, et al., 2008; Munafo, Brown, & Hariri, 2008; Pezawas, et al., 2005). One study found an slight epistatic effect of BDNF and 5-HTTLPR on the grey matter volume of the amygdala (Pezawas, et al., 2008). Therefore, in study III, it is investigated if such an interaction effect could be substantiated for the amygdala and additionally revealed for the hippocampus. The results of the current thesis allow further comprehension of recollection, hence episodic memory, and point to a special role of the BDNF in temporal and prefrontal brain regions. Additionally, the finding of an epistatic effect between BDNF and serotonin transporter function point to the need of analyzing interactions between genes and also between genes and environmental factors which reveals more information than the study of main effects alone. In conclusion, analyzing behavioral and neural correlates of episodic memory reveal allowed insights in brain functions that may serve as guideline for future studies in clinical populations with memory deficits, including susceptibility factors such as good or bad environment, as well as promising gene variants that influence episodic memory

Elongation factor P: Function and effects on bacterial fitness.

The elongation phase of translation is promoted by three universal elongation factors, EF-Tu, EF-Ts, and EF-G in bacteria and their homologs in archaea and eukaryotes. Recent findings demonstrate that the translation of a subset of mRNAs requires a fourth elongation factor, EF-P in bacteria or the homologous factors a/eIF5A in other kingdoms of life. EF-P prevents the ribosome from stalling during the synthesis of proteins containing consecutive Pro residues, such as PPG, PPP, or longer Pro clusters. The efficient and coordinated synthesis of such proteins is required for bacterial growth, motility, virulence, and stress response. EF-P carries a unique post-translational modification which contributes to its catalytic proficiency. The modification enzymes, which are lacking in higher eukaryotes, provide attractive new targets for the development of new, highly specific antimicrobials

Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics