@article{FroehlichPapenfortBergeretal.2012, author = {Fr{\"o}hlich, Kathrin S. and Papenfort, Kai and Berger, Allison A. and Vogel, J{\"o}rg}, title = {A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {8}, doi = {10.1093/nar/gkr1156}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134230}, pages = {3623-3640}, year = {2012}, abstract = {A remarkable feature of many small non-coding RNAs (sRNAs) of Escherichia coli and Salmonella is their accumulation in the stationary phase of bacterial growth. Several stress response regulators and sigma factors have been reported to direct the transcription of stationary phase-specific sRNAs, but a widely conserved sRNA gene that is controlled by the major stationary phase and stress sigma factor, Sigma(S) (RpoS), has remained elusive. We have studied in Salmonella the conserved SdsR sRNA, previously known as RyeB, one of the most abundant stationary phase-specific sRNAs in E. coli. Alignments of the sdsR promoter region and genetic analysis strongly suggest that this sRNA gene is selectively transcribed by Sigma(S). We show that SdsR down-regulates the synthesis of the major Salmonella porin OmpD by Hfq-dependent base pairing; SdsR thus represents the fourth sRNA to regulate this major outer membrane porin. Similar to the InvR, MicC and RybB sRNAs, SdsR recognizes the ompD mRNA in the coding sequence, suggesting that this mRNA may be primarily targeted downstream of the start codon. The SdsR-binding site in ompD was localized by 3'-RACE, an experimental approach that promises to be of use in predicting other sRNA-target interactions in bacteria.}, language = {en} } @article{HagemannAnackerErnestusetal.2012, author = {Hagemann, Carsten and Anacker, Jelena and Ernestus, Ralf-Ingo and Vince, Giles H.}, title = {A complete compilation of matrix metalloproteinase expression in human malignant gliomas}, series = {World Journal of Clinical Oncology}, volume = {3}, journal = {World Journal of Clinical Oncology}, number = {5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123982}, pages = {67-79}, year = {2012}, abstract = {Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory data available. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.}, language = {en} } @phdthesis{Platt2012, author = {Platt, Christian}, title = {A Common Thread in Unconventional Superconductivity: The Functional Renormalization Group in Multi-Band Systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78824}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Die supraleitenden Eigenschaften von komplexen Materialsystemen, wie den erst k{\"u}rzlich entdeckten Eisen-Pniktiden oder den Strontium-Ruthenaten, sind oftmals durch das Zusammenspiel vieler elektronischer Orbitale bestimmt. Um die Supraleitung in derartigen Systemen besser zu verstehen, entwickeln wir in dieser Arbeit eine Multi-Orbital-Implementierung der funktionalen Renormierungsgruppe und untersuchen die Elektronenpaarung in verschiedenen charakteristischen Materialverbindungen. In den Eisen-Pniktiden finden wir hierbei mehrere Spinfluktuationskan{\"a}le, die eine Elektronenpaarung hervorrufen, sofern die Paarwellenfunktion einen Vorzeichenwechsel zwischen den verschiedenen genesteten Bereichen der Fermifl{\"a}che aufweist. Abh{\"a}ngig von den spezifischen Materialeigenschaften, wie der Dotierung oder der Position des Pniktogenatoms, f{\"u}hren diese Spinfluktuationen dann zu \$s_{\pm}\$-wellenartiger Paarung mit durchg{\"a}ngiger Energiel{\"u}cke oder mit Knoten auf der Fermifl{\"a}che. In manchen F{\"a}llen wird zudem auch \$d\$-wellenartige Paarung induziert, die in der N{\"a}he des {\"U}bergangs zur \$s_{\pm}\$-Symmetrie einen gemischten \$(s+id)\$-Zustand mit gebrochener Zeitinversionssymmetrie aufweist. Diese neuartige Phase zeigt faszinierende Eigenschaften, wie zum Beispiel das spontane Entstehen von Suprastr{\"o}men am Probenrand und um nichtmagnetische St{\"o}rstellen. Auf Grund der durchg{\"a}ngigen Energiel{\"u}cke ist dieser \$(s+id)\$-Zustand energetisch beg{\"u}nstigt. Im Folgenden untersuchen wir zudem auch die elektronischen Instabilit{\"a}ten eines weiteren außergew{\"o}hnlichen Materials -- dotiertes Graphen. Diese rein zweidimensionale Kohlenstoffverbindung ist schon seit mehreren Jahren im Fokus der Festk{\"o}rperforschung und wurde mittlerweile auch durch neuartige experimentelle Verfahren dotiert, ohne die zugrundeliegende hexagonale Gittersturktur merklich zu st{\"o}ren. Eine theoretische Beschreibung dieses Systems erfordert die Ber{\"u}cksichtigung zweier nicht-equivalenter Gitterpl{\"a}tze, was wiederum effektiv als Zwei-Orbital-System aufgefasst werden kann. Durch die besondere Symmetrie der hexagonalen Gitterstruktur sind beide \$d\$-wellenartigen Paarungskan{\"a}le entartet und ahnlich der \$(s+id)\$-Paarung in den Pniktiden finden wir hier eine chirale \$(d+id)\$-Paarung in einem weiten Dotierungsbereich um van-Hove F{\"u}llung. Des Weiteren identifizieren wir Spin-Triplet-Paarung und eine exotische Form der Spindichtewelle, welche beide durch leichte Ver{\"a}nderung der langreichweitigen H{\"u}pfamplituden und Wechselwirkungensparameter realisiert werden k{\"o}nnen. Als drittes Beispiel betrachten wir die Supraleitung in dem Strontium-Ruthenat Sr\$_2\$RuO\$_4\$. Die Besonderheit dieser Materialverbindung liegt in der m{\"o}glichen Realisierung einer chiralen Spin-Triplet Paarung, die wiederum faszinierende Eigenschaften wie die Existenz von halbganzzahligen Flussvortizes mit nicht-Abelscher Vertauschungsstatistik aufweisen w{\"u}rde. Mittels eines mikroskopischen Drei-Orbital-Modells und der Ber{\"u}cksichtigung von Spin-Bahn-Kopplung finden wir hierbei, dass moderate ferromagnetische Spinfluktuationen immer noch ausreichen, um diesen speziellen Paarungszustand anzutreiben. Die berechnete Energiel{\"u}cke zeigt im Weiteren sehr starke Anisotropien auf dem \$d_{xy}\$-Orbital-dominierten Bereich der Fermifl{\"a}che und verschwindet nahezu vollst{\"a}ndig auf den anderen beiden Fermifl{\"a}chen.}, subject = {Supraleitung}, language = {en} } @article{HomolaJbabdiBeckmannetal.2012, author = {Homola, Gy{\"o}rgy A. and Jbabdi, Saad and Beckmann, Christian F. and Bartsch, Andreas J.}, title = {A Brain Network Processing the Age of Faces}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75513}, year = {2012}, abstract = {Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.}, subject = {Medizin}, language = {en} } @article{LiSamnickLapaetal.2012, author = {Li, Xiang and Samnick, Samuel and Lapa, Constantin and Israel, Ina and Buck, Andreas K. and Kreissl, Michael C. and Bauer, Wolfgang}, title = {68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76231}, year = {2012}, abstract = {Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2\%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2\%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.}, subject = {Medizin}, language = {en} } @phdthesis{Fuchs2012, author = {Fuchs, Andreas Rudolf}, title = {3D-Pulverdruck von Zellkulturtr{\"a}gern mit Magnesium-Phosphat-Chemie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77415}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {In der vorliegenden Arbeit wurden erstmals im 3D-Pulerdruckverfahren hergestellte Struvit-Matrizes auf ihre Eignung als Tr{\"a}germaterial f{\"u}r Knochenzellen in vitro untersucht. Hierzu wurde die Zytokompatibilit{\"a}t sowie die chemische L{\"o}slichkeit von gedruckten Struvit-Strukturen betrachtet. In einem zweiten Schritt wurde untersucht, ob die biologische Funktion von BMP-2-L{\"o}sungen nach Durchlaufen des Druckprozesses erhalten bleibt und ob es m{\"o}glich ist, BMP-2 unter Beibehaltung seiner biologischen Wirksamkeit direkt in Struvit-Matrizes zu drucken. Als Reaktanten zur Herstellung der Struvit-Matrizes wurde modifiziertes Farringtonit-Pulver mit definierter K{\"o}rnung und eine {\"a}quimolare Binder-L{\"o}sung aus DAHP und ADHP verwendet. Die untersuchten Zellkulturtr{\"a}ger mit Magnesiumammoniumphosphatchemie zeigten eine ausreichende Zytokompatibilit{\"a}t in vitro. Außerdem wurde gezeigt, dass thermolabile Proteine wie BMP-2 im 3D-Pulverdruckverfahren unter weitgehender Beibehaltung ihrer biologischen Wirksamkeit in vitro grunds{\"a}tzlich prozessierbar sind. Die Freisetzung direkt eingedruckter Proteine aus den Struvit-Matrizes blieb jedoch hinter den Erwartungen zur{\"u}ck. Mit Struvit steht ein alternatives Zementsystem f{\"u}r den 3D-Pulverdruck zur Verf{\"u}gung, welches spezifische Vorteile gegen{\"u}ber den etablierten Calciumphosphaten bietet. Weitere Untersuchungen sind erforderlich, um die Ursache f{\"u}r die geringe BMP-Freisetzung aus den Struvit-Matrizes zu ermitteln und die Vorteile der neutralen Abbindereaktion voll nutzen zu k{\"o}nnen.}, subject = {Struvit}, language = {de} } @article{FinzeReissFrohn2012, author = {Finze, Maik and Reiss, Guido J. and Frohn, Hermann-Josef}, title = {2,3,5,6-Tetrafluoro-1,4-bis(trimethylsilyl)benzene}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75401}, year = {2012}, abstract = {no abstract available}, subject = {Chemie}, language = {en} } @article{KlotzMentrupRegensburgeretal.2012, author = {Klotz, Barbara and Mentrup, Birgit and Regensburger, Martina and Zeck, Sabine and Schneidereit, Jutta and Schupp, Nicole and Linden, Christian and Merz, Cornelia and Ebert, Regina and Jakob, Franz}, title = {1,25-Dihydroxyvitamin D3 Treatment Delays Cellular Aging in Human Mesenchymal Stem Cells while Maintaining Their Multipotent Capacity}, series = {PLoS ONE}, volume = {7}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0029959}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133392}, pages = {e29959}, year = {2012}, abstract = {1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, beta-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence-and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to beta-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging.}, language = {en} } @phdthesis{Zimmerer2012, author = {Zimmerer, Daniel Johannes}, title = {"Plasmodium falciparum - changes under treatment" : Eine lichtmikroskopische Studie morphologischer {\"A}nderungen von Plasmodium falciparum unter Therapie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76597}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Die H{\"a}lfte der Weltbev{\"o}lkerung lebt mit dem Risiko, an einer schweren Malaria tropica zu erkranken. Zunehmende Resistenzen von Plasmodium falciparum gegen g{\"a}ngige Therapeutika erschweren eine Behandlung, und es existiert keine M{\"o}glichkeit fr{\"u}hzeitig die Wirksamkeit der angewandten Medikation festzustellen. Die Bestimmung der Parasit{\"a}mie als einzig verf{\"u}gbarer Parameter kann auch bei erfolgreicher Therapie noch {\"u}ber den ersten Tag ansteigen. Das Ziel dieser Studie war, lichtmikroskopische Parameter zu finden, mit denen der Erfolg einer Therapie fr{\"u}hzeitig festgestellt werden kann. So wurden im Rahmen einer Fallstudie die Plasmodien eines an einer schweren Malaria tropica erkrankten Patienten auf morphologische Ver{\"a}nderungen im Verlauf der Chinin-Therapie untersucht. Die Beurteilung der Plasmodien erfolgte durch eine Einteilung nach ihrer Lage im Erythrozyten und der Kern-Plasma-Relation der Ringformen, anschliessend wurden die Ergebnisse durch eine Vermessung der Plasmodien am Computer verifiziert. Es zeigte sich, dass ein Therapieerfolg anhand der Ver{\"a}nderung in der Morphologie der Ringformen bereits in den ersten Stunden nach Therapiebeginn festgestellt werden kann. So l{\"a}sst sich innerhalb der ersten drei Stunden ein Wechsel von kleinen Ringformen mit d{\"u}nnem, homogenem Zytoplasmaband zu vergr{\"o}sserten Ringformen mit einem verbreiterten und inhomogenen Zytoplasma finden. Im weiteren konnten ab der 7. Therapiestunde eine zunehmende Lagever{\"a}nderungen der Plasmodien im Erythrozyten aufgezeigt werden. So waren ab diesem Zeitpunkt zunehmend Plasmodien, die die Erythrozyten-Membran hervorw{\"o}lben (Arbeitstitel „Accentu{\´e}"-Formen), im peripheren Blutausstrich des Patienten zu sehen. Dass die {\"A}nderung der Kern-Plasma-Relation der Ringformen urs{\"a}chlich einer direkten Medikamentenwirkung zuzuschreiben sind, konnte in einem abschliessenden „in vitro"-Studienteil gezeigt werden, in welchem Plasmodien-Kulturen unter Chinin-Einfluss mit Kontrollkulturen ohne Medikamenteneinfluss verglichen wurden.}, subject = {Malaria tropica}, language = {de} } @article{GuederBrennerAngermannetal.2012, author = {G{\"u}der, G{\"u}lmisal and Brenner, Susanne and Angermann, Christiane E. and Ertl, Georg and Held, Matthias and Sachs, Alfred P. and Lammers, Jan Willem and Zanen, Peter and Hoes, Arno W. and St{\"o}rk, Stefan and Rutten, Frans H.}, title = {"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75193}, year = {2012}, abstract = {Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed postbronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Agedependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28\%) patients, and the three LLNs misclassified 114 (46\%), 96 (39\%), and 98 (40\%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 \% predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50\% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.}, subject = {Medizin}, language = {en} }