Long-Term Behavior of Defined Mixed Cultures of Geobacter sulfurreducens and Shewanella oneidensis in Bioelectrochemical Systems

This work aims to investigate the long-term behavior of interactions of electrochemically active bacteria in bioelectrochemical systems. The electrochemical performance and biofilm characteristics of pure cultures of Geobacter sulfurreducens and Shewanella oneidensis are being compared to a defined mixed culture of both organisms. While S. oneidensis pure cultures did not form cohesive and stable biofilms on graphite anodes and only yielded 0.034 ± 0.011 mA/cm2 as maximum current density by feeding of each 5 mM lactate and acetate, G. sulfurreducens pure cultures formed 69 μm thick, area-wide biofilms with 10 mM acetate as initial substrate concentration and yielded a current of 0.39 ± 0.09 mA/cm2. Compared to the latter, a defined mixed culture of both species was able to yield 38% higher maximum current densities of 0.54 ± 0.07 mA/cm2 with each 5 mM lactate and acetate. This increase in current density was associated with a likewise increased thickness of the anodic biofilm to approximately 93 μm. It was further investigated whether a sessile incorporation of S. oneidensis into the mixed culture biofilm, which has been reported previously for short-term experiments, is long-term stable. The results demonstrate that S. oneidensis was not stably incorporated into the biofilm; rather, the planktonic presence of S. oneidensis has a positive effect on the biofilm growth of G. sulfurreducens and thus on current production

Long-Term Behavior of Defined Mixed Cultures of Geobacter sulfurreducens and Shewanella oneidensis in Bioelectrochemical Systems

This work aims to investigate the long-term behavior of interactions of electrochemically active bacteria in bioelectrochemical systems. The electrochemical performance and biofilm characteristics of pure cultures of Geobacter sulfurreducens and Shewanella oneidensis are being compared to a defined mixed culture of both organisms. While S. oneidensis pure cultures did not form cohesive and stable biofilms on graphite anodes and only yielded 0.034 ± 0.011 mA/cm2 as maximum current density by feeding of each 5 mM lactate and acetate, G. sulfurreducens pure cultures formed 69 μm thick, area-wide biofilms with 10 mM acetate as initial substrate concentration and yielded a current of 0.39 ± 0.09 mA/cm2. Compared to the latter, a defined mixed culture of both species was able to yield 38% higher maximum current densities of 0.54 ± 0.07 mA/cm2 with each 5 mM lactate and acetate. This increase in current density was associated with a likewise increased thickness of the anodic biofilm to approximately 93 μm. It was further investigated whether a sessile incorporation of S. oneidensis into the mixed culture biofilm, which has been reported previously for short-term experiments, is long-term stable. The results demonstrate that S. oneidensis was not stably incorporated into the biofilm; rather, the planktonic presence of S. oneidensis has a positive effect on the biofilm growth of G. sulfurreducens and thus on current production

Quantitation of the A2A Adenosine Receptor Density in the Striatum of Mice and Pigs with [18F]FLUDA by Positron Emission Tomography.

The cerebral expression of the A2A adenosine receptor (A2AAR) is altered in neurodegenerative diseases such as Parkinson's (PD) and Huntington's (HD) diseases, making these receptors an attractive diagnostic and therapeutic target. We aimed to further investigate the pharmacokinetic properties in the brain of our recently developed A2AAR-specific antagonist radiotracer [18F]FLUDA. For this purpose, we retrospectively analysed dynamic PET studies of healthy mice and rotenone-treated mice, and conducted dynamic PET studies with healthy pigs. We performed analysis of mouse brain time-activity curves to calculate the mean residence time (MRT) by non-compartmental analysis, and the binding potential (BPND) of [18F]FLUDA using the simplified reference tissue model (SRTM). For the pig studies, we performed a Logan graphical analysis to calculate the radiotracer distribution volume (VT) at baseline and under blocking conditions with tozadenant. The MRT of [18F]FLUDA in the striatum of mice was decreased by 30% after treatment with the A2AAR antagonist istradefylline. Mouse results showed the highest BPND (3.9 to 5.9) in the striatum. SRTM analysis showed a 20% lower A2AAR availability in the rotenone-treated mice compared to the control-aged group. Tozadenant treatment significantly decreased the VT (14.6 vs. 8.5 mL · g-1) and BPND values (1.3 vs. 0.3) in pig striatum. This study confirms the target specificity and a high BPND of [18F]FLUDA in the striatum. We conclude that [18F]FLUDA is a suitable tool for the non-invasive quantitation of altered A2AAR expression in neurodegenerative diseases such as PD and HD, by PET

The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain

Peer reviewe

Evaluation der Experimentierklausel nach § 6c SGB II - Vergleichende Evaluation des arbeitsmarktpolitischen Erfolgs der Modelle der Aufgabenwahrnehmung "Optierende Kommune" und "Arbeitsgemeinschaft"; Untersuchungsfeld 2: Implementations- und Governanceanalyse; Zwischenbericht Mai 2007 an das BMAS

Zwischenbericht 2007 der FH Frankfurt, Institut für Stadt- und Regionalentwicklung, und des Instituts für angewandte Sozialwissenschaft (infas) zur Implementations- und Governanceanalyse im Rahmen der Evalouation der Experimentierklausel nach § 6c SGB II. Die Implementations- und Governanceanalyse untersucht die Umsetzung der durch das SGB II definierten Leistungsprozesse anhand einer Stichprobe von 154 regionalen Einheiten aus allen Arbeitsgemeinschaften (ARGEn), zugelassenen kommunalen Trägern und Fällen getrennter Aufgabenwahrnehmung. Der Bericht analysiert im ersten Teil überregionale Governance-Strukturen (z. B. rechtliche und finanzielle Vorgaben, Zielvereinbarungen), die Auswirkungen auf die Leistungserbringung der SGB II-Einheiten haben. Im zweiten Teil werden die lokalen Steuerungs- und Organisationsstrukturen in den Formen der Aufgabenwahrnehmung untersucht und wird eine Typologie der Organisation des Leistungsprozesses entwickelt. Der dritte Teil beschäftigt sich mit der Ausgestaltung der Schnittstellen zwischen SGB II, SGB III und SGB VIII, insbesondere im Hinblick auf Eingliederungsleistungen für Jugendliche und junge Erwachsene sowie die Organisation der Arbeitsvermittlung

Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET) in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-)clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012

Challenges on Cyclic Nucleotide Phosphodiesterases Imaging with Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights since 2016

Cyclic nucleotide phosphodiesterases (PDEs) represent one of the key targets in the research field of intracellular signaling related to the second messenger molecules cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP). Hence, non-invasive imaging of this enzyme class by positron emission tomography (PET) using appropriate isoform-selective PDE radioligands is gaining importance. This methodology enables the in vivo diagnosis and staging of numerous diseases associated with altered PDE density or activity in the periphery and the central nervous system as well as the translational evaluation of novel PDE inhibitors as therapeutics. In this follow-up review, we summarize the efforts in the development of novel PDE radioligands and highlight (pre-)clinical insights from PET studies using already known PDE radioligands since 2016

Signal-peptide-peptidase-like 2a is required for CD74 intramembrane proteolysis in human B cells

The invariant chain (CD74) mediates targeting of the MHCII complex to endosomal compartments, where CD74 undergoes degradation allowing MHCII to acquire peptides. We demonstrated recently that intramembrane proteolysis of the final membrane-bound N-terminal fragment (NTF) of CD74 is catalysed by Signal-peptide-peptidase-like 2a (SPPL2a) and that this process is indispensable for development and function of B lymphocytes in mice. In SPPL2a(−/−) mice, homeostasis of these cells is disturbed by the accumulation of the unprocessed CD74 NTF. So far, evidence for this essential role of SPPL2a is restricted to mice. Nevertheless, inhibition of SPPL2a has been suggested as novel approach to target B cells for treating autoimmunity. Here, we characterize human B cell lines with a homozygous microdeletion on chromosome 15. We demonstrate that this deletion disrupts the SPPL2a genomic locus and leads to loss of SPPL2a transcript. Lymphoblastoid cell lines from patients with this deletion exhibit absence of SPPL2a at the protein level and show an accumulation of the CD74 NTF comparable to B cells from SPPL2a(−/−) mice. By this means, we present evidence that the role of SPPL2a in CD74 proteolysis is conserved in human B cells and provide support for modulation of SPPL2a activity as a therapeutic concept

Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET) in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-)clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we report on the syntheses of three novel fluoroalkylated triazine derivatives (TA2–4) and on the evaluation of their effect on the enzymatic activity of human PDE2A. The most potent PDE2A inhibitors were 18F-radiolabelled ([18F]TA3 and [18F]TA4) and investigated regarding their potential as PET radioligands for imaging of PDE2A in mouse brain. In vitro autoradiography on rat brain displayed region-specific distribution of [18F]TA3 and [18F]TA4, which is consistent with the expression pattern of PDE2A protein. Metabolism studies of both [18F]TA3 and [18F]TA4 in mice showed a significant accumulation of two major radiometabolites of each radioligand in brain as investigated by micellar radio-chromatography. Small-animal PET/MR studies in mice using [18F]TA3 revealed a constantly increasing uptake of activity in the non-target region cerebellum, which may be caused by the accumulation of brain penetrating radiometabolites. Hence, [18F]TA3 and [18F]TA4 are exclusively suitable for in vitro investigation of PDE2A. Nevertheless, further structural modification of these promising radioligands might result in metabolically stable derivatives