Iron and its neighbors, earth-abundant hydrogenation catalysts for the synthesis of heterocycles and ethers

This thesis discusses the topic of earth-abundant metals in hydrogenation catalysis. Firstly, a new family of manganese PNN-pincer catalysts was developed for the hydrogenation of quinolines at ambient temperature. Secondly, an iron-Tetraphos system was discovered that allows direct N-aryl pyrrole synthesis from nitroarenes in a hydrogenation/Paal-Knorr cascade. Lastly, the effect of phosphine oxide promoters on cobalt carbonyl precatalysts was evaluated, leading to improved protocols for the reductive etherification of aldehydes and the reductive or carbonylative transformation of oxetanes.Diese Arbeit behandelt das Thema der häufig-vorkommenden Metalle in der Hydrierkatalyse. Zuerst berichten wir über eine neue Gruppe von Mangan-PNN-Pincer Katalysatoren für die Hydrierung von Chinolinderivaten bei Raumtemperatur. Als nächstes wird ein Eisen-Tetraphos-System für die direkte Synthese von N-Arylpyrrolen aus Nitroarenen mithilfe einer Transferhydrierungs-/Paal-Knorr-Kaskade präsentiert. Zuletzt evaluieren wir den positiven Effekt von Phosphinoxid-Promotoren auf Cobaltcarbonyl-Präkatalysatoren in der reduktiven Etherifizierung von Aldehyden und der Umwandlung von Oxetanen

Circulation and Oxygen Distribution in the Tropical Atlantic Cruise No. 80, Leg 1; October 26 to November 23, 2009 Mindelo (Cape Verde) to Mindelo (Cape Verde)

METEOR cruise 80/1 was a contribution to the SFB 754 “Climate-Biogeochemistry Interactions in the Tropical Ocean”. Shipboard, glider and moored observations are used to study the temporal and spatial variability of physical and biogeochemical parameters within the oxygen minimum zone (OMZ) of the tropical North Atlantic. As part of the BMBF “Nordatlantik” project, it further focuses on the equatorial current system including the Equatorial Undercurrent (EUC) and intermediate currents below. During the cruise, hydrographic station observations were performed using a CTD/O2 rosette, including water sampling for salinity, oxygen, nutrients and other biogeochemical tracers. Underway current measurements were successfully carried out with the 75 kHz ADCP borrowed from R/V POSEIDON during the first part of the cruise, and R/V METEOR’s 38 kHz ADCP during the second part. During M80/1, an intensive mooring program was carried out with 8 mooring recoveries and 8 mooring deployments. Right at the beginning of the cruise, a multidisciplinary mooring near the Cape Verde Islands was recovered and redeployed. Within the framework of SFB 754, two moorings with CTD/O2 profilers were recovered and redeployed with other instrumentation in the center and at the southern rim of the OMZ of the tropical North Atlantic. The equatorial mooring array as part of BMBF “North Atlantic” project consists of 5 current meter moorings along 23°W between 2°S and 2°N. It is aimed at quantifying the variability of the thermocline water supply toward the equatorial cold tongue which develops east of 10°W during boreal summer. Several glider missions were performed during the cruise. One glider was recovered that was deployed two months earlier. Another glider was deployed for two short term missions, near the equator for about 8 days and near 8°N for one day. This glider was equipped with a new microstructure probe in addition to standard sensors, i.e. CTD/O2, chlorophyll and turbidity

The influence of immune aging on the pathogenesis of osteoporosis and rheumatoid arthritis

HintergrundDas Altern von Zellen beeinflusst unser Leben enorm. \uc4ltere Menschen sind anf\ue4lliger f\ufcr Infektionen, Krebs- und Autoimmunerkrankungen. Bei der Rheumatoider Arthritis handelt es sich um eine Erkrankung, die im Alter geh\ue4uft auftritt und mit einer Zerst\uf6rung von Knochen einhergeht. In dieser Arbeit stellen wir die Hypothese auf, dass es eine Verbindung zwischen Knochenschwund und einer vorzeitigen Alterung des Immunsystems gibt. Deshalb untersuchen wir die Pr\ue4valenz gealterter T Zellen bei Patienten mit RA und deren F\ue4higkeit das Knochenabbau-f\uf6rdernde Protein RANKL zu produzieren.MethodenBei 41 RA Patienten den Patienten wurde eine Knochendichtemessung durchgef\ufchrt. Mittels FACS wurde die Expression von RANKL auf CD28+CD45RA+, CD28+ CD45RO+ und CD28- der CD4+ und CD8+ Populationen gemessen. In Zellkultur-Experimenten wurde die RANKL-Expression nach Behandlung mit verschiedenen Stimulanzien untersucht. ResultateDie Pr\ue4valenz der CD4+CD28- T Zellen der RA Patienten betrug 1.4% bzw. CD8+ 41.7%. RANKL wurde auf CD4+CD28- T Zellen h\ue4ufiger detektiert als auf CD4+CD28+CD45RA+ oder auf CD4+CD28+CD45RO+ T Zellen. Im Gegensatz dazu wiesen CD8+CD28- T Zellen eine geringere Expression von RANKL als naive und Ged\ue4chtnis-Zellen auf. In der Folge konnte eine signifikante Steigerung der Anzahl an RANKL-positiven T Zellen durch Stimulation mit IL-15 gezeigt werden. Die Steigerung wurde vor allem in Ged\ue4chtnis- und CD28- Zellen beobachtet.Die Pr\ue4valenz der zirkulierenden CD4+CD28- T Zellen zeigte eine inverse Korrelation zum Ergebnis der DEXA Messung, w\ue4hrend f\ufcr die CD8+CD28- T Zell Population lediglich ein Trend f\ufcr eine negative Assoziation zu beobachten war. SchlussfolgerungCD4+CD28- T Zellen sind mit dem Auftreten von Knochenschwund bei der RA assoziiert. Da CD4+CD28- T Zellen auch h\ue4ufiger RANKL an der Oberfl\ue4che exprimieren als andere CD4+ T Zell Subsets kann ein direkter Einfluss dieser Zellen auf den Knochenabbau vermutet werden.BackgroundAging affects the immune system and elderly people are more susceptible to diseases caused by immune failure. Rheumatoid arthritis and osteoporosis are associated with systemic bone loss and occur more frequently in old age. It is known that premature immunosenescence contributes to the pathogenesis of RA whereas its role for the evolvement of bone loss is not well understood. I worked on the hypothesis that aging of T cells is linked with bone loss. For this reason, we examine the prevalence of aged T cells in patients with RA with and without bone loss. In functional assays we test the mechanisms how aged T cells might induce bone resorption.Methods41 patients underwent measurement of bone density. The prevalence of naive, memory and CD28- among the CD4+ and CD8+ populations were determined by flow cytometry. In addition to staining resting cells for RANKL, RANKL expression was measured after cell culture with several stimulants. ResultsThe prevalence of CD4+CD28- and CD8+CD28- T cells in our RA cohort was 1.4% and 41.7%. RANKL was more frequently expressed on CD4+CD28- T cells compared to naive and memory T cells. In contrast, CD8+CD28- T cells expressed RANKL less frequently than na\uefve and memory CD8+ T cells. Furthermore, a significant increase of the number of RANKL+ T cells was noted after stimulation with IL-15. This increase was mainly observed in memory and CD28- T cells.The levels of circulating CD4+CD28- were inversely correlated with the results of the DEXA measurement, whereas for the CD8+CD28- T cell population we observed a trend only. Patients with reduced bone mass showed a higher prevalence of CD4+CD28- T cells compared to patients with normal bone mass. ConclusionAged CD4+CD28- T cells are associated with the occurrence of bone loss in RA. As CD4+CD28- T cells express surface RANKL more frequently than other CD4+ subsets, a direct influence of these cell population in the pathogenesis of osteoclastogenesis is possible.eingereicht von Johannes FesslerGraz, Univ., Masterarb., 2012Zsfassung in dt. und engl. Sprach

Localization of the Antennapedia protein in Drosophila embryos and imaginal discs

Antibodies have been raised against a fusion protein containing the 3' region of the coding sequence of the Antennapedia (Antp) gene fused to β-galactosidase. The distribution of the protein on whole mount embryos and imaginal discs of third instar larvae was examined by immunofluorescence. In young embryos, expression of the Antp protein was limited to the thoracic segments in the epidermis, whereas it was found in all neuromeres of head, thorax and abdomen. At the end of embryogenesis, the Antp protein mainly accumulated in the ventral nervous system in certain parts of the thoracic neuromeres, from posterior T1 to anterior T3, with a gap in posterior T2. Comparison of Antp protein distribution in nervous systems from wild-type and Df P9 embryos, lacking the genes of the Bithorax-complex (BX-C), revealed a pattern of expression which indicated that the BX-C represses Antp in the posterior segments with the exception of the last abdominal neuromeres (A8-9) which are regulated independently. The protein pattern in nervous systems from Sex combs reduced(Scr(xF9)) mutant embryos was indistinguishable from that found in wild-type embryos; thus, neurogenic expression of Antp in T1 and the more anterior segments does not appear to be under the control of Scr(+). All imaginal discs derived from the three thoracic segments express Antp protein. The distribution was distinct in each disc; strongest expression was observed in the proximal parts of the discs. In the leg discs the protein distribution seemed to be compartmentally restricted, whereas in the wing disc this was not the case. Antp protein was not detected in the eye-antennal disc. In embryos, as well as in imaginal discs, the protein is localized in the nucleus

Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the  pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases

Effects of Probiotic Strains on Disease Activity and Enteric Permeability in Psoriatic Arthritis–A Pilot Open-Label Study

(1) Background: Psoriatic Arthritis (PsA) is a painful disease of the joints and spine. Recent reports observed distinct enteric dysbiosis in PsA; intake of probiotic strains is considered to ameliorate enteric dysbiosis. If probiotics are effective in PsA is elusive. (2) Methods: In this pilot open-label study we enrolled 10 PsA patients with low to medium disease activity who received probiotics for 12 weeks. Analysis of faecal zonulin, α1-antitrypsin and calprotectin, as well as peripheral immune phenotyping was performed at baseline, after 12 weeks and 12 weeks after termination of probiotic intake. (3) Results: All patients showed increased levels of the enteric permeability marker zonulin which correlated with the frequency of peripheral Th17 cells. Calprotectin, a marker for intestinal inflammation was elevated in 6 out of 10 patients. Probiotic intake resulted in a reduction of disease activity and gut permeability. These effects, however, were not sustained beyond termination of probiotic intake. (4) Conclusions: PsA patients suffer from enhanced enteric permeability and inflammation. Probiotics may ameliorate disease activity in PsA by targeting these alterations