Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans

A microsomal cytochrome P-450-NADPH dependent enzyme which hydroxylates stereo- and regiospecifically carbon atom 14 of (S)- -N- methyltetrahydroprotoberberines has been discovered in a number of plant cell cultures originating from species containing protopine alkaloids; the monooxygenase was solubilized, partially purified (100-fold) and characterized

Entwicklung einer Methode zur Verwendung der Daten des Schornsteinfegerhandwerks für die energiewirtschaftliche Berichterstattung

Der Einsatz von Holz in Kleinfeuerungsanlagen ist ein wichtiger Baustein der erneuerbaren Wärmebereitstellung. Vertiefende Informationen zu diesem Anlagenpark liegen auf Bundesebene jedoch nicht vor. Vor diesem Hintergrund wurde in dieser Arbeit eine Methode zur Quantifizierung und Charakterisierung des Bestands an biomassebasierten Kleinfeuerungsanlagen und Abschätzung des Brennstoffeinsatzes entwickelt. Diese Arbeit umfasst neben den angewandten Methoden einen umfangreichen Ergebnisteil, der den Bestand an Kleinfeuerungstechnologien quantifiziert und hinsichtlich des eingesetzten Brennstoffsortiments, Leistungs- und Altersklassen charakterisiert sowie den anlagenbezogenen und kumulierten Brennstoffeinsatz ausweist

Patterning of stem cells during limb regeneration in Ambystoma mexicanum

Axolotl uniquely generates blastema cells as a pool of progenitor/stem cells to restore an entire limb, a particular property that other organisms, such as humans, do not have. What underlies these differences? Is the main difference that cells residing at the amputation plane (in the stump) undergo reprogramming processes to re-enter the embryonic program, which allows developmental patterning to start, or are there fundamental differences? There is also a significant debate about whether regeneration occurs via stem cell differentiation or by dedifferentiation of mature limb tissue. The aim of my thesis was to address following questions: Are the cells in the blastema reprogrammed or differentiated to regenerate? Are the blastema cells genetically reactivated de novo during regeneration? How does the amputated limb exactly know which part of the limb needs to be regenerate? Using a novel technique of long-term genetic fate mapping, my team demonstrated that dedifferentiation in regenerated axolotl muscle tissue does not occur. Instead, PAX7+ satellite cells indeed play an important role during muscle regeneration in the axolotl limb. Surprisingly, this is in contrast to the newt, which regenerates muscle cells through a dedifferentiation process. Therefore, there is a fundamental difference that underlies the regenerative mechanism ((Sandoval-Guzman et al., 2014) [KR1]). This demonstrates that there is an unexpected diversity and flexibility of cellular mechanims used during limb regeneration, even among two closely related species. Finally, if one salamander species uses a mammalian regenerative strategy (Cornelison and Wold, 1997; Collins et al., 2005) involving stem cells and another uses a dedifferentiative strategy, this raises the question of whether there are other fundamental aspects of regeneration that could also be anomalous. This hypothesis is promising since there could be more than one possible mechanism to induce mammalian regeneration. The process of limb regeneration in principle seems to be more similar to those of limb development as historically assumed. We showed molecularly that embryonic players are reused during regeneration by reactivating the position- and tissue-specific developmental gene programs by using the newly isolated Twist sequences as early blastema cell markers ((Kragl et al., 2013) [KR2]). To gain insights into the molecular mechanisms of the P/D limb patterning in general, it was crucial to study the early patterning events of the resident progenitor/stem cells by using the specific blastema cell marker HoxA as a positional marker along the proximo-distal axis. Our HOXA protein analysis using high molecular and cellular resolution as well as transplantation assays demonstrated for the first time that axolotl limb blastema cells acquire their positional identity in a proximal to distal sequence. We found a hierarchy of cellular restrictions in positional identities. Amputation at the level of the upper arm showed that the blastema harbors cells, which convert to lower arm and hand. We observed ((Roensch et al., 2013) [KR3]) for the first time that intercalation- the intermediate element (lower arm) arises later from an interaction between the proximal and distal cells identities- does not occur. Intercalation, which has been an accepted model for a long time, is not the patterning mechanism underlying normal (without any manipulation) limb regeneration that is unique to axolotl. We further demonstrated, using the Hox genes as markers that positional identity is cell-type specific since their effects were confirmed to be present in the lateral plate mesoderm- derived cells of the limb. As our knowledge about limb blastemas expands concerning cell composition and molecular events controlling patterning, the similarity to development is becoming more and more clear. My work has resolved many ambiguities surrounding the molecularly identification of different types of blastema cells and how P/D limb patterning occurs during regeneration in comparison to development. It has highlighted the importance of combining high-resolution methods, such as in situ hybridizations, single-cell PCR (sc-PCR) of individual dissociated blastema cells and genetic labeling methods with grafting experiments to map cell fates in vivo. In addition to understanding the processes of regeneration, another long-term goal in the regenerative medicine field is to identify key molecules that trigger the regeneration of tissues. Recently, my colleague Takuji Sugiura (Sugiura et al., 2016) observed that an early event of blastema formation is the secretion of molecules like MLP (MARCKS-like protein), which induces wound-associated cell cycle re-entry. Such findings further increase the enthusiasm of biologists to understand the underlying principles of regeneration. By building our knowledge of the molecules and pathways that are involved in tissue regeneration, we increase the possibility of identifying a way to ‘activate’ regenerative processes in humans and thus reach the final goal of regenerative medicine, which is to use the concepts of cellular reprogramming, stem cell biology and tissue engineering to repair complex body structures

Wertwandel und Protestwahlverhalten am Beispiel potentieller Wähler Grüner Listen

In dem Beitrag wird untersucht, inwiefern sich aus den Mustern der Unzufriedenheit mit einer Reihe vorgegebener politischer Probleme Hinweise auf den genaueren Charakter der Abhängigkeit der Sympathie für Grüne Listen vom Wertwandel etwa im Inglehartschen Sinn ergeben. Darüber hinaus wird eine Operationalisierung des politischen Protestes der Anhänger Grüner Listen anhand der Differenziertheit bzw. Generalisierung der Unzufriedenheit mit politischen Issues (problembezogene Protestdimension) und derjenigen mit politischen Akteuren bzw. Aspekten des politischen Systems (adressatenbezogene Protestdimension) vorgenommen. Anhand von Wahlergebnissen der Grünen Liste wird geprüft, ob sich außer den bekannten Hochburgen wie etwa Gorleben oder studentisch geprägten Wohnbezirken in den Großstädten räumliche Protest-Muster anhand von Stimmanteilen sowie soziostrukturellen Merkmalen der Wahlgebiete identifizieren lassen. Aus der Berücksichtigung von Traditionen der Betroffenheit und des Protests und des räumlichen Milieus werden Hinweise auf Überlagerungseffekte aus anderen Protesttraditionen sowie auf die Richtung einer etwaigen Mobilisierbarkeit insbesondere von Neuwählern herausgearbeitet. Datengrundlagen sind ausgewählte Stimmbezirkswahlergebnisse aus Kommunal- und Landtagswahlen und zwei von EMNID durchgeführte Umfragen von Juni und Oktober 1978. Bei gleicher Frageformulierung über Grüne Listen wurden jeweils eine Reihe von Einstellungen zu unterschiedlichen politischen Problemen und zum politischen System erfragt. Für die Kontrastgruppe wurden Gegner der Grünen Listen ausgewählt. (RW

Blinder Fleck: Studierende der Klasse Bruno Raetsch, Kunsthochschule Burg Giebichenstein Halle, stellen aus : 19. Mai-27. Juni 2018

Der Katalog erscheint anlässlich der Ausstellung BLINDER FLECK. Studierende der Klasse Bruno Raetsch, Kunsthochschule Burg Giebichenstein Halle, stellen aus. Jenaer Kunstverein, 19. Mai bis 27. Juni 201

Which outcomes have been measured in hand eczema trials? A systematic review:A systematic review

The considerable heterogeneity of outcomes and measurement instruments in hand eczema trials substantially limits the evidence synthesis concerning therapeutic and preventive interventions. Therefore, the Hand Eczema Core Outcome Set (HECOS) initiative is developing a core outcome set for future trials. The first objective was to identify outcomes that were measured in previous trials, to group them in domains, and to identify their measurement instruments. We conducted a systematic review of controlled and randomized controlled hand eczema trials published since 2000. Sixty-one eligible studies were identified. Each assessed one or more of 47 outcomes in the "skin" domain. Eighteen trials (30%) additionally focused on preventive behaviour in risk occupations. Quality of life was measured in 13 studies (21%). Thirty-two distinct named instruments were applied, but 223 measurements (62%) were conducted with unnamed instruments. Only 32 studies (52%) defined a primary outcome. Twenty-nine trials (48%) provided some information on adverse events, but none gave any references concerning relevant methods. Our review confirms the need to harmonize outcome measurements in hand eczema trials. The findings form the basis for a consensus process to generate a core outcome set to improve the explanatory power and comparability of future hand eczema studies.</p

Circulating DNA as prognostic biomarker in patients with advanced hepatocellular carcinoma: a translational exploratory study from the SORAMIC trial

Abstract: Background: Liquid biopsy based on cell-free DNA circulating in plasma has shown solid results as a non-invasive biomarker. In the present study we evaluated the utility of circulating free DNA (cfDNA) and the sub-type tumor DNA (ctDNA) in hepatocellular cancer (HCC) patients to assess therapy response and clinical outcome. Methods: A cohort of 13 patients recruited in the context of the SORAMIC trial with unresectable, advanced HCC and different etiological and clinicopathological characteristics was included in this exploratory study. Plasma samples were collected between liver micro-intervention and beginning of sorafenib-based systemic therapy and then in correspondence of three additional follow-ups. DNA was isolated from plasma and next generation sequencing (NGS) was performed on a panel of 597 selected cancer-relevant genes. Results: cfDNA levels showed a significant correlation with the presence of metastases and survival. In addition cfDNA kinetic over time revealed a trend with the clinical history of the patients, supporting its use as a biomarker to monitor therapy. NGS-based analysis on ctDNA identified 28 variants, detectable in different combinations at the different time points. Among the variants, HNF1A, BAX and CYP2B6 genes showed the highest mutation frequency and a significant association with the patients’ clinicopathological characteristics, suggesting a possible role as driver genes in this specific clinical setting. Conclusions: Taken together, the results support the prognostic value of cfDNA/ctDNA in advanced HCC patients with the potential to predict therapy response. These findings support the clinical utility of liquid biopsy in advanced HCC improving individualized therapy and possible earlier identification of treatment responders

IER2-induced senescence drives melanoma invasion through osteopontin

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence