Spleißvarianten der Glycinrezeptor-β-Untereinheit in Zelllinien des Kleinzelligen Bronchialkarzinoms

Glycine receptors play an essential role in the central nervous system as mediator of inhibitory transmission and in this way in inhibition of neuronal activity. The functional receptor consists of five subunits α and β and binds to the postsynaptic protein gephyrin. Subunits exist in different splice variants. Beside the classical receptor located in the central nervous system, the subunit βΔ8 could be found in cell lines of small cell lung cancer. In the following thesis, constructs of gephyrin were created for further fishing experiments and the βΔ8 subunit was characterized biochemically.Der Glycinrezeptor spielt im Zentralen Nervensystem eine essentielle Rolle bei der Vermittlung inhibitorischer Übertragung und damit bei der Hemmung neuronaler Aktivität. Der funktionale Rezeptor setzt sich aus insgesamt fünf α- und β-Untereinheiten zusammen und bindet postsynaptisch an das Protein Gephyrin. Die Untereinheiten des Rezeptors existieren in verschiedenen Spleißvarianten. Neben dem Vorliegen des klassischen Rezeptors im ZNS konnte u.a. die Spleißvariante βΔ8 auf RNA-Ebene in Zelllinien des Kleinzelligen Bronchialkarzinoms nachgewiesen werden. In der vorliegenden Arbeit wurden Gephyrin-Konstrukte für weiterführende Fishing-Experimente geschaffen sowie die Spleißvariante βΔ8 biochemisch charakterisiert

Despite large choice of effective therapies: Individuals with psoriasis still seem undertreated

Summary Background and objectives Due to the development of new anti‐psoriatic drugs in combination with improved structures for implementation throughout Germany, the medical care of psoriasis patients has markedly improved. In this study we investigated the real‐life utilization of the health care system and identified reasons for dissatisfaction in affected individuals. Patients and methods This non‐interventional cross‐sectional study was conducted as an anonymous online survey from 12/2018 to 01/2019 in Germany. Participants with a self‐reported physician‐confirmed diagnosis of psoriasis and symptoms answered questions about their disease, its influence on daily life and their medical care. Results 649 participants with a mean age of 42.5 ± 13.7 years and equal gender distribution (male: 50.2 %) were evaluated. 54.1 % received medical treatment at the time of the study, 45.9 % did not. Among the participants with medical care, 59.3 % were only moderately or less satisfied with their treatment. Reasons for dissatisfaction with the medication included lack of efficacy and side effects. Participants without medical treatment specified a physician’s lack of time as a main reason for not seeking medical help. Conclusions Despite the availability of efficient therapeutic options in Germany, many individuals with psoriasis are not satisfied. This under‐treated group was identified as a new target population

Alternative activation of human macrophages enhances tissue factor expression and production of extracellular vesicles

Macrophages are versatile cells that can be polarized by the tissue environment to fulfill required needs. Proinflammatory polarization is associated with increased tissue degradation and propagation of inflammation whereas alternative polarization within a Th2 cytokine environment is associated with wound healing and angiogenesis. To understand if polarization of macrophages can lead to a procoagulant macrophage subset we polarized human monocyte derived macrophages to a proinflammatory and an alternative activation state. Alternative polarization with interleukin-4 and IL-13 led to a macrophage phenotype characterized by increased tissue factor (TF) production and release and by an increase in extracellular vesicle production. In addition, also TF activity was enhanced in extracellular vesicles of alternatively polarized macrophages. This TF induction was dependent on signal transducer and activator of transcription-6 signaling and poly ADP ribose polymerase activity. In contrast to monocytes, human macrophages did not show increased tissue factor expression upon stimulation with lipopolysaccharide and interferon-γ. Previous polarization to either a proinflammatory or an alternative activation subset does not change the subsequent stimulation of TF. The inability of proinflammatory activated macrophages to respond to lipopolysaccharide and interferon-γ with an increase in TF production seems to be due to an increase in TF promoter methylation and was reversible when treating these macrophages with a demethylation agent. In conclusion, we provide evidence that proinflammatory polarization of macrophages does not lead to enhanced procoagulatory function, whereas alternative polarization of macrophages leads to an increased expression of TF and increased production of TF bearing extracellular vesicles by these cells suggesting a procoagulatory phenotype of alternatively polarized macrophages

SAM levels, gene expression of SAM synthetase, methionine synthase and ACC oxidase, and ethylene emission from N. suaveolens flowers

S′adenosyl-l-methionine (SAM) is a ubiquitous methyl donor and a precursor in the biosynthesis of ethylene, polyamines, biotin, and nicotianamine in plants. Only limited information is available regarding its synthesis (SAM cycle) and its concentrations in plant tissues. The SAM concentrations in flowers of Nicotiana suaveolens were determined during day/night cycles and found to fluctuate rhythmically between 10 and 50 nmol g−1 fresh weight. Troughs of SAM levels were measured in the evening and night, which corresponds to the time when the major floral scent compound, methyl benzoate, is synthesized by a SAM dependent methyltransferase (NsBSMT) and when this enzyme possesses its highest activity. The SAM synthetase (NsSAMS1) and methionine synthase (NsMS1) are enzymes, among others, which are involved in the synthesis and regeneration of SAM. Respective genes were isolated from a N. suaveolens petal cDNA library. Transcript accumulation patterns of both SAM regenerating enzymes matched perfectly those of the bifunctional NsBSMT; maximum mRNA accumulations of NsMS1 and NsSAMS1 were attained in the evening. Ethylene, which is synthesized from SAM, reached only low levels of 1–2 ppbv in N. suaveolens flowers. It is emitted in a burst at the end of the life span of the flowers, which correlates with the increased expression of the 1-aminocyclopropane-1-carboxylate oxidase (NsACO)

Current and emerging developments in subseasonal to decadal prediction

Weather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Splice variants of the glycine receptor β subunit in cell lines of small cell lung cancer

Der Glycinrezeptor spielt im Zentralen Nervensystem eine essentielle Rolle bei der Vermittlung inhibitorischer Übertragung und damit bei der Hemmung neuronaler Aktivität. Der funktionale Rezeptor setzt sich aus insgesamt fünf α- und β-Untereinheiten zusammen und bindet postsynaptisch an das Protein Gephyrin. Die Untereinheiten des Rezeptors existieren in verschiedenen Spleißvarianten. Neben dem Vorliegen des klassischen Rezeptors im ZNS konnte u.a. die Spleißvariante βΔ8 auf RNA-Ebene in Zelllinien des Kleinzelligen Bronchialkarzinoms nachgewiesen werden. In der vorliegenden Arbeit wurden Gephyrin-Konstrukte für weiterführende Fishing-Experimente geschaffen sowie die Spleißvariante βΔ8 biochemisch charakterisiert.Glycine receptors play an essential role in the central nervous system as mediator of inhibitory transmission and in this way in inhibition of neuronal activity. The functional receptor consists of five subunits α and β and binds to the postsynaptic protein gephyrin. Subunits exist in different splice variants. Beside the classical receptor located in the central nervous system, the subunit βΔ8 could be found in cell lines of small cell lung cancer. In the following thesis, constructs of gephyrin were created for further fishing experiments and the βΔ8 subunit was characterized biochemically

Geostandards and Geoanalytical Research Bibliographic Review 2021

This GGR Bibliographic Review is a survey of approximately 5200 geoanalytical publications for the year 2021. Selected articles, numbering over 340, containing measurement results for relevant geological and environmental reference materials are listed with individual summaries of target analytes, relevant reference materials and producers. A brief summary of a selection of these publications is included that highlights notable developments in geoanalytical studies, newly developed or characterised RMs, and new datasets of established reference materials that have been re‐analysed using improved or state‐of‐the‐art measurement techniques.Key Points: Literature review of 5200 geoanalytical publications for the year 2021. 344 selected articles with summaries of target analytes, relevant reference materials and producers. Selected publications include data obtained by new analytical developments and improved analytical protocols for established RMs, and identifies recently developed RMs for specific scientific topics.http://georem.mpch-mainz.gwdg.de