Funktionelle Analyse des ANGUSTIFOLIA-Gens aus Arabidopsis thaliana

Meine Doktorarbeit besteht aus zwei Teilen, der Kontrolle der Organbildung und der Kontrolle der Zellform von Blatthaaren und Epidermiszellen aus Arabidopsis thaliana. In vaskulären Pflanzen besteht das apikale Sproßmeristem aus drei Gewebeschichten, der L1, der L2 und der L3 Schicht. Die Schichten werden während der Organbildung getrennt gehalten und ergeben später die Epidermis, das Grundgewebe und das vaskuläre System. Ziel dieser Studie war unter zu Hilfenahme der angustifolia (an) Mutante, die sich durch einen schmalblättrigen Phänotyp auszeichnet, die Beteiligung der einzelnen Gewebeschichten an der Blattentwicklung aufzuschlüsseln. Meine Daten zeigen, dass AN ein zellautonomes Protein ist. Die Expression von AN in der Subepidermis, nicht aber die Expression in der Epidermis, rettet auf einem nicht zellautonomen Weg den schmalblättrigen Phänotyp. Aus meinen Beobachtungen schließe ich, dass Wachstumsänderungen, die durch die Subepidermis herbeigeführt werden, in der Epidermis durch Änderungen der Zellzahl und nicht der Zellgröße kompensiert werden. Die Zellmorphogenese wurde anhand von Blatthaaren (Trichome) und Epidermiszellen untersucht. an Mutanten unterscheiden sich vom Wildtyp in der Anzahl der Trichomverzweigungen und durch das fehlende Auswachsen der Epidermiszellen. AN kodiert für ein Protein mit Sequenzähnlichkeiten zu Proteinen, die sich durch zwei unterschiedliche Funktionen auszeichnen, der CtBP/BARS (der Corepressor �C-terminal binding protein� und das Golgi regulierende �Brefeldin A ribosylated substrate�) Familie. an Mutanten werden durch CtBP aus Drosophila vollständig gerettet. Da jedoch Proteine, die das Konsensus- Motiv, welches das Drosophila CtBP bindet, AN nicht binden, ist es unwahrscheinlich, dass die Corepressor Funktion des CtBPs aus Drosophila in Pflanzen von Relevanz ist. Das deutet darauf hin, dass AN für die Funktion des Golgis wichtig ist. Die AN:YFP Fusion, die eine Version von AN enthält, die nicht mehr dimerisieren kann, unterstützt diese Vermutung, da, die Lokalisierung der Golgi-Verteilung ähnelt. Die Rolle von AN bei der räumlichen Regulation der Zellmorphogenese wurde in Epidermiszellen analysiert. AN:YFP lokalisiert in den Wachstumsregionen, den Auswölbungen der Zellen, was darauf hindeutet, dass AN an der lokalen Umgestaltung des Golgis beteiligt ist. Mutationsanalysen des AN Proteins legen nahe, dass eine mögliche Phosphorylierungs-Stelle wichtig für die Funktion ist. Außerdem interagiert AN mit einer Proteinkinase im Hefe Zwei-Hybrid Tests, somit ist es wahrscheinlich, dass die Aktivität von AN durch seinen Phosphorylierungsstatus reguliert wird

Catalogers Unite! Creating Documentation through Collaboration

Recent changes have forced Bowling Green State University (BGSU) to reevaluate our documentation, workflows, and communication. There have been staff retirements, changes in staff responsibilities, and a new faculty cataloger. Additionally, BGSU is implementing a discovery layer, purchasing shelf-ready books, and adding more electronic resources. It has become apparent that documentation needs to be updated and, in many cases, created from scratch. Collaboration is critical as catalogers are currently few in number and are seeing the need to work with other departments in ways unheard of previously. The creation of a new cataloging manual is vital to the success of cataloging at BGSU

Atmospheric Influences on Space-Based Observations of Extremely High-Energy Cosmic Rays

Air showers in the Earth\u27s atmosphere emit UV light detectable from space. The impact of atmospheric conditions on light emission/transmission has been studied for a space-based CR observatory. The importance of scattering/ground reflection on the fraction of Cherenkov and fluorescence light received is pointed out. Measuring UV light from above, the attenuation by the ozone layer cannot be disregarded. Based upon air shower simulation, quantitative numbers of ozone attenuation are presented

Polar boundary layer bromine explosion and ozone depletion events in the chemistry-climate model EMAC v2.52: Implementation and evaluation of AirSnow algorithm

Ozone depletion events (ODEs) in the polar boundary layer have been observed frequently during springtime. They are related to events of boundary layer enhancement of bromine. Consequently, increased amounts of boundary layer volume mixing ratio (VMR) and vertical column densities (VCDs) of BrO have been observed by in situ observation, ground-based as well as airborne remote sensing, and from satellites. These so-called bromine explosion (BE) events have been discussed serving as a source of tropospheric BrO at high latitudes, which has been underestimated in global models so far. We have implemented a treatment of bromine release and recycling on sea-ice- and snow-covered surfaces in the global chemistry–climate model EMAC (ECHAM/MESSy Atmospheric Chemistry) based on the scheme of Toyota et al. (2011). In this scheme, dry deposition fluxes of HBr, HOBr, and BrNO3 over ice- and snow-covered surfaces are recycled into Br2 fluxes. In addition, dry deposition of O3, dependent on temperature and sunlight, triggers a Br2 release from surfaces associated with first-year sea ice. Many aspects of observed bromine enhancements and associated episodes of near-complete depletion of boundary layer ozone, both in the Arctic and in the Antarctic, are reproduced by this relatively simple approach. We present first results from our global model studies extending over a full annual cycle, including comparisons with Global Ozone Monitoring Experiment (GOME) satellite BrO VCDs and surface ozone observations

Bortezomib in antibody-mediated autoimmune diseases (TAVAB): study protocol for a unicentric, non-randomised, non-placebo controlled trial

Introduction: The clinical characteristics of autoantibodymediated autoimmune diseases are diverse. Yet, medical treatment and the associated complications are similar, that is, the occurrence of long-term side effects and the problem that a significant proportion of patients are non-responders. Therefore, new therapeutic options are needed. Bortezomib, a proteasome inhibitor, is effective in the treatment of multiple myeloma and data from experimental models and case reports suggest an effect in the treatment of autoantibody-mediated autoimmunity. In our study, we will determine the effect of bortezomib treatment on a shared surrogate parameter for clinical efficacy, namely change in autoantibody levels, which we chose as primary parameter. Methods and analysis: We designed a phase IIa trial with altogether n=18 treatment-refractory patients suffering from myasthenia gravis, systemic lupus erythematosus and rheumatoid arthritis that will be treated with bortezomib add-on to pre-existing therapy. Primary endpoint is the change in autoantibody levels 6 months after therapy. Secondary endpoints include concomitant medication, disease-specific clinical scores and measures of quality of life and activities of daily living. Ethics and dissemination: Safety parameters include neurophysiological and clinical signs of peripheral neuropathy as well as potential central nervous system side effects determined by olfactory and neuropsychological testing. The study has been approved by the local ethical committee and first participants have already been enrolled. This proof of concept study will contribute to improve our understanding of plasma cellspecific treatment approaches by assessing its safety and efficacy in reducing serum levels of antibodies known to mediate autoimmune disorders. We plan to publish the final results of our study in a peer reviewed journal and to present our findings at international conferences. Trial registration number: NCT02102594

Brominated VSLS and their influence on ozone under a changing climate

Very short-lived substances (VSLS) contribute as source gases significantly to the tropospheric and stratospheric bromine loading. At present, an estimated 25 % of stratospheric bromine is of oceanic origin. In this study, we investigate how climate change may impact the ocean–atmosphere flux of brominated VSLS, their atmospheric transport, and chemical transformations and evaluate how these changes will affect stratospheric ozone over the 21st century. Under the assumption of fixed ocean water concentrations and RCP6.0 scenario, we find an increase of the ocean–atmosphere flux of brominated VSLS of about 8–10 % by the end of the 21st century compared to present day. A decrease in the tropospheric mixing ratios of VSLS and an increase in the lower stratosphere are attributed to changes in atmospheric chemistry and transport. Our model simulations reveal that this increase is counteracted by a corresponding reduction of inorganic bromine. Therefore the total amount of bromine from VSLS in the stratosphere will not be changed by an increase in upwelling. Part of the increase of VSLS in the tropical lower stratosphere results from an increase in the corresponding tropopause height. As the depletion of stratospheric ozone due to bromine depends also on the availability of chlorine, we find the impact of bromine on stratospheric ozone at the end of the 21st century reduced compared to present day. Thus, these studies highlight the different factors influencing the role of brominated VSLS in a future climate

Development of a Non-invasive Methodology for the Assessment of Muscle Fibre Composition

The percentage area of fast twitch fibres of a muscle is a major determinant of muscle mechanical power and, thus, an important biomarker for the evaluation of training processes. However, the invasive character of the assessment (muscle biopsy) limits the wide application of the biomarker in the training praxis. Our purpose was to develop a non-invasive method for the assessment of fast twitch fibre content in human soleus muscle. From a theoretical point of view, the maximum muscle mechanical power depends on the fibre composition, the muscle volume and muscle specific tension. Therefore, we hypothesised that the percentage area of type II fibres would show a correlation with the maximum muscle mechanical power normalised to muscle volume and specific muscle contractile strength (i.e., plantar flexion moment divided by muscle cross-sectional area). In 20 male adults, the percentage area of type II fibres, volume and maximum cross-sectional area of the soleus muscle as well as the maximum plantar flexion moment and the maximum mechanical power were measured using muscle biopsies, magnetic resonance imaging and dynamometry. The maximum mechanical power normalised to muscle volume and specific muscle contractile strength provided a significant relationship (r = 0.654, p = 0.002) with the percentage area of type II fibres. Although the proposed assessment parameter cannot fully replace histological measurements, the predictive power of 43% can provide a relevant contribution to performance diagnostics in the training praxis

Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC

The vulnerability of northern European vegetation to ozone damage in a changing climate. An assessment based on current knowledge

The potential vulnerability of vegetation at northern latitudes to ozone damage was assessed based on current knowledge with regard to air ozone concentrations and leaf ozone uptake as well as to plant traits affecting ozone tolerance. The focus was on the northern European arctic, alpine and northern boreal vegetation zones, with a special focus on high-altitude vegetation. In particular, we analysed if there are increasing risks for ozone impacts on northern vegetation due to high spring ozone concentrations in relation to climate change induced shifts such as e.g. an earlier start of the growing season. The current state of knowledge implies that ecosystems in the far north are not more susceptible to ozone than vegetation in other parts of Europe. Hence, we cannot advocate for a stronger reduction of ozone precursors emissions based exclusively on the ozone sensitivity of vegetation in the far north. Thus, policies designed to reduce emissions of ozone precursors to protect vegetation in other parts of Europe as well as in the entire northern hemisphere are likely to suffice to protect vegetation in northern Fennoscandia.The report describes an assessment of the potential vulnerability of far northern European vegetation to ozone damage in a changing climate. Scientists from Sweden, Norway and Finland have joined in and the assessments rely on the experience and expertise of the authors. We could not find evidence that expected changes in ozone concentrations and climate would make the northern arctic, alpine and subalpine vegetation substantially more vulnerable to ozone than other types of European vegetation

Effect of everolimus-based drug regimens on CMV-specific T-cell functionality after renal transplantation: 12-month ATHENA subcohort-study results

Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA-study completing the 12-month visit on-treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV-specific CD4 T cells were determined after stimulation with CMV-antigen, and cytokine-profiles and various T-cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC-treated patients had CMV-infections, no such events were reported in EVR-treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV-specific T cells, their median expression of CTLA-4 and PD-1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA-4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV-specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR-treated patients retained CMV-specific T-cell functionality, which may contribute to enhanced protection against CMV infections