471 research outputs found
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 and 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
and by means of thermodynamic Bethe ansatz for the anisotropy
, 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 and , 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
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