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Kiesewetter, Barbara ; Cherny, Nathan I. ; Boissel, Nicolas ; Cerisoli, Francesco ; Dafni, Urania ; Vries, Elisabeth G. E. de ; Ghia, Paolo ; Gökbuget, Nicola ; González-Calle, Verónica ; Huntly, Brian ; Jäger, Ulrich ; Latino, Nicola Jane ; Douillard, Jean-Yves ; Malcovati, Luca ; Mateos, Maria-Victoria ; Ossenkoppele, Gert J. ; Porkka, Kimmo ; Raderer, Markus ; Ribera, Josep-Maria ; Scarfò, Lydia ; Wester, Ruth ; Zygoura, Panagiota ; Sonneveld, Pieter
Objective: Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology—Magnitude of Clinical Benefit Scale (ESMO-MCBS).
Methods: Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies.
Results: In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described.
Conclusions: Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials.
Der Bericht fasst den Verlauf und die vorläufigen Ergebnisse des Projekts „Gender und Romanistik: Studien- und Berufsentscheidungen Studierender am Fachbereich 10“ zusammen, welches dank der finanziellen Unterstützung durch den Ruth-Moufang-Fonds und den Fachbereich 10 der GU zwischen Dezember 2018 und September 2019 unter der Leitung von Anna-Christine Weirich durchgeführt werden konnte.
Das Interesse des Projekts besteht darin, einerseits die Entscheidungsprozesse besser nachvollziehen zu können, die bei den heutigen Studierenden der Romanistik an der GU zu ihrer Studienwahl geführt haben. Andererseits geht es darum, mehr darüber zu erfahren, welche beruflichen Ziele und Vorstellungen diese Studierenden haben und welche Ängste und Sorgen dabei zu Tage treten. Vom 1. bis 31. Dezember 2018 wurde mit Hilfe des webbasierten Umfrage-Editors EvaSys eine schriftliche Online-Umfrage unter den Studierenden der Romanistik durchgeführt, die den Titel „Luftfahrttechnik, Landschaftsbau – oder doch Romanistik? Etappen und Entscheidungen auf dem Weg ins Romanistikstudium“ trug. Der Fragebogen umfasst ca. 55 Fragen, unterteilt in 6 Fragebereiche. Neben demographischen Daten und Informationen zu den studierten Fächern handelt es sich dabei um einen Fragekomplex „Familie“, in dem es vor allem darum geht, ob wichtige Bezugspersonen Einfluss auf Studien- und Berufsentscheidungen genommen haben und falls ja, wie; einen Fragekomplex zum Thema Schule, in dem es um fachliche Neigungen, die Förderung durch das Lehrpersonal sowie Angebote zur Berufsorientierung geht. 133 Studierende beteiligten sich an der Umfrage, was einem Rücklauf von etwa 11% entspricht.
Diese Arbeit nimmt Weiße Freiwillige aus Deutschland in den Blick, die einen Freiwilligendienst im Ausland geleistet haben und in rassistischen Machtverhältnissen eine privilegierte, das heißt Weiße Position einnehmen. Dabei dienen die Critical Whiteness Studies als fruchtbare Grundlage, um die Auseinandersetzung mit Rassismus aus Weißer privilegierter Perspektive zu untersuchen. Die Arbeit geht daher der Frage nach: Inwiefern die Erfahrungen im Freiwilligendienst und die begleitenden rassismuskritischen Seminare Weiße Nord-Nord und Nord-Süd Freiwillige dazu anregen, ihre Privilegien zu reflektieren und sich kritisch im rassistischen Machtsystem zu positionieren. Die Analyse der Interviews mit Weißen Freiwilligen zeigt, dass die Interviewten zum einen unterschiedliche Konfrontationserfahrungen mit Whiteness gemacht haben und zum anderen ihre daraus resultierenden Reflexionsprozesse und Umgangsweisen sehr divers ausfallen. Unterschiede zeigen sich jedoch nicht nur zwischen den Nord-Nord und Nord-Süd Freiwilligen, sondern auch situationsabhängig anhand der jeweiligen Erfahrungen der einzelnen Weißen Freiwilligen. Aus diesen Untersuchungen lässt sich ableiten, dass es auch für rassismus- und machtkritische Begleitseminare weiterhin eine zu bewältigende Herausforderung bleibt, die Relevanz der persönlichen Auseinandersetzung mit Whiteness und somit mit eigenen Privilegien und Verstrickungen in Rassismus – unabhängig vom Zielland des Freiwilligendienstes – zu vermitteln.
Uni-Highlights März 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
leporello #3
(2020)
In dieser Ausgabe werfen wir unter anderem einen Blick zurück – auf die Lange Nacht der Kleinen Fächer und die Abschlusstagung des BMBF-Projektes "Die Sammlung als lebendiges Archiv".Wir berichten über aktuelle Ausstellungen und sagen Ihnen, was Sie die nächsten Monate nicht verpassen sollten! Das Objekt des Moments ist selbstverständlich auch wieder dabei!
Roick, Julia ; Berner, Reinhard ; Bernig, Toralf ; Erdlenbruch, Bernhard ; Escherich, Gabriele ; Faber, Jörg ; Klein, Christoph ; Bochennek, Konrad ; Kratz, Christian ; Kühr, Joachim ; Längler, Alfred ; Lode, Holger ; Metzler, Markus ; Müller, Hermann ; Reinhardt, Dirk ; Sauerbrey, Axel ; Schepper, Florian ; Scheurlen, Wolfram ; Schneider, Dominik ; Schwabe, Georg Christof ; Richter, Matthias
Background: About 2000 children and adolescents under the age of 18 are diagnosed with cancer each year in Germany. Because of current medical treatment methods, a high survival rate can be reached for many types of the disease. Nevertheless, patients face a number of long-term effects related to the treatment. As a result, physical and psychological consequences have increasingly become the focus of research in recent years. Social dimensions of health have received little attention in health services research in oncology so far. Yet, there are no robust results that allow an estimation of whether and to what extent the disease and treatment impair the participation of children and adolescents and which factors mediate this effect. Social participation is of great importance especially because interactions with peers and experiences in different areas of life are essential for the development of children and adolescents.
Methods: Data are collected in a longitudinal, prospective, observational multicenter study. For this purpose, all patients and their parents who are being treated for cancer in one of the participating clinics throughout Germany will be interviewed within the first month after diagnosis (t1), after completion of intensive treatment (t2) and half a year after the end of intensive treatment (t3) using standardized questionnaires. Analysis will be done by descriptive and multivariate methods.
Discussion: The results can be used to identify children and adolescents in high-risk situations at an early stage in order to be able to initiate interventions tailored to the needs. Such tailored interventions will finally reduce the risk of impairments in the participation of children and adolescents and increase quality of life.
Trial registration: ClinicalTrials.gov: NCT04101123.
Tascón, Igor ; Sousa, Joana Sofia de ; Corey, Robin A. ; Mills, Deryck J. ; Griwatz, David ; Aumüller, Nadine ; Mikusevic, Vedrana ; Stansfeld, Phillip J. ; Vonck, Janet ; Hänelt, Inga
Potassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins.
Posch, Nicole ; Horvath, Karl ; Wratschko, Kerstin ; Plath, Jasper ; Brodnig, Richard ; Siebenhofer-Kroitzsch, Andrea
Background: Patient information materials and decision aids are essential tools for helping patients make informed decisions and share in decision-making. The aim of this study was to investigate the quality of the written patient information materials available at general practices in Styria, Austria.
Methods: We asked general practitioners to send in all patient information materials available in their practices and to answer a short questionnaire. We evaluated the materials using the Ensuring Quality Information for Patients (EQIP-36) instrument.
Results: A total of 387 different patient information materials were available for quality assessment. These materials achieved an average score of 39 out of 100. The score was below 50 for 78% of all materials. There was a significant lack of information on the evidence base of recommendations. Only 9 % of the materials provided full disclosure of their evidence sources. We also found that, despite the poor quality of the materials, 89% of general practitioners regularly make active use of them during consultations with patients.
Conclusion: Based on international standards, the quality of patient information materials available at general practices in Styria is poor. The vast majority of the materials are not suitable as a basis for informed decisions by patients. However, most Styrian general practitioners use written patient information materials on a regular basis in their daily clinical practice. Thus, these materials not only fail to help raise the health literacy of the general population, but may actually undermine efforts to enable patients to make shared informed decisions. To increase health literacy, it is necessary to make high quality, evidence-based and easy-to-understand information material available to patients and the public. For this, it may be necessary to set up a centralized and independent clearinghouse.
Sorting nexins are a conserved protein family involved in vesicle transport, membrane trafficking and protein sorting. The sorting nexin ATG24/SNX4 has been demonstrated to be involved in different autophagy pathways and in endosomal trafficking. However, its impact on cellular quality control and on aging and development is still elusive. Here we report studies analyzing the function of PaATG24 in the aging model Podospora anserina. Ablation of PaATG24 leads to a reduced growth rate, infertility, and to a pronounced lifespan reduction. These characteristics are accompanied by alterations of the morphology and size distribution of vacuoles and severe impairments in non-selective and selective autophagy of peroxisomes (pexophagy) and mitochondria (mitophagy). While general autophagy and pexophagy are almost completely blocked, a PaATG24-independent form of mitophagy is induced during aging. In the ΔPaAtg24 mutant a strong accumulation of peroxisomes occurs while mitochondrial abundance is only slightly increased. These mitochondria are partially affected in function. Most strikingly, although some PaATG24-independent mitophagy exists, it appears that this is not sufficient to remove dysfunctional mitochondria efficiently enough to prevent premature aging. Overall our data emphasize the key role of mitochondria in aging and of mitophagy in quality control to keep a population of “healthy” mitochondria during aging.
Background: Research on desired emotions revealed that individuals want to feel negative emotions if they expect these emotions to yield certain benefits. In previous studies, the pursuit of sadness (e.g., via pursuing art that evokes sadness) has been attributed to hedonic motives, i.e., to feel pleasure. We propose that in individuals with major depressive disorder (MDD) the pursuit of sadness may be more strongly related to self-verification motives, i.e., to sustain their sense of self through feeling sad.
Methods: Participants with MDD (n = 50) were compared to non-depressed controls (n = 50) in their desired emotional states, as indicated by selected music (sad, happy and neutral), and in their motives (hedonic vs. self-verification) for choosing sad music. Groups were also compared in their self-reported general preference for sadness and the perceived functionality of sadness.
Results: MDD participants showed a significant higher desire for sadness; more than half of them deliberately chose sad music. Whereas MDD participants had a marked preference for self-verification over hedonic motives, the reverse was true for non-depressed controls. MDD participants also agreed more strongly with self-verifying functions of sadness and expressed a stronger general preference for sadness.
Conclusion: Findings indicate that emotion regulation in MDD might be driven by self-verification motives. They point to the relevance of exploring patients’ desired emotional states and associated motives. The systematic integration of positive affect into the self-image of depressed patients might help to deemphasize the self-verifying function of sadness, thereby overcoming the depression.
Dual antiplatelet treatment (DAPT) increases the risk of tPA-associated hemorrhagic transformation (HT) in ischemic stroke. To investigate the effects of DAPT in rodents, reliable indicators of platelet function utilizing a minimally invasive procedure are required. We here established a fluorescence-based assay to monitor DAPT efficiency in a mouse model of ischemic stroke with HT. Male C57/BL6 mice were fed with aspirin and clopidogrel (ASA+CPG). Venous blood was collected, stimulated with thrombin, labeled with anti-CD41-FITC and anti-CD62P-PE, and analyzed by flow cytometry. Subsequently, animals were subjected to experimental stroke and tail bleeding tests. HT was quantified using NIH ImageJ software. In ASA+CPG mice, the platelet activation marker CD62P was reduced by 40.6 ± 4.2% (p < 0.0001) compared to controls. In vitro platelet function correlated inversely with tail bleeding tests (r = −0.8, p = 0.0033, n = 12). Twenty-four hours after drug withdrawal, platelet activation rates in ASA+CPG mice were still reduced by 20.2 ± 4.1% (p = 0.0026) compared to controls, while tail bleeding volumes were increased by 4.0 ± 1.4 μl (p = 0.004). Conventional tests using light transmission aggregometry require large amounts of blood and thus cannot be used in experimental stroke studies. In contrast, flow cytometry is a highly sensitive method that utilizes small volumes and can easily be incorporated into the experimental stroke workflow. Our test can be used to monitor the inhibitory effects of DAPT in mice. Reduced platelet activation is indicative of an increased risk for tPA-associated cerebral hemorrhage following experimental stroke. The test can be applied to individual animals and implemented flexibly prior and subsequent to experimental stroke.
The insertion of membrane proteins requires proteinaceous complexes in the cytoplasm, the membrane, and the lumen of organelles. Most of the required complexes have been described, while the components for insertion of β‐barrel‐type proteins into the outer membrane of chloroplasts remain unknown. The same holds true for the signals required for the insertion of β‐barrel‐type proteins. At present, only the processing of Toc75‐III, the β‐barrel‐type protein of the central chloroplast translocon with an atypical signal, has been explored in detail. However, it has been debated whether Toc75‐V/ outer envelope protein 80 (OEP80), a second protein of the same family, contains a signal and undergoes processing. To substantiate the hypothesis that Toc75‐V/OEP80 is processed as well, we reinvestigated the processing in a protoplast‐based assay as well as in native membranes. Our results confirm the existence of a cleavable segment. By protease protection and pegylation, we observed intermembrane space localization of the soluble N‐terminal domain. Thus, Toc75‐V contains a cleavable N‐terminal signal and exposes its polypeptide transport‐associated domains to the intermembrane space of plastids, where it likely interacts with its substrates.
Müller, Stephan ; Bexte, Tobias ; Gebel, Veronika ; Kalensee, Franziska ; Stolzenberg, Eva ; Hartmann, Jessica ; Köhl, Ulrike ; Schambach, Axel ; Wels, Winfried ; Modlich, Ute ; Ullrich, Evelyn
Autologous chimeric antigen receptor-modified (CAR) T cells with specificity for CD19 showed potent antitumor efficacy in clinical trials against relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Contrary to T cells, natural killer (NK) cells kill their targets in a non-antigen-specific manner and do not carry the risk of inducing graft vs. host disease (GvHD), allowing application of donor-derived cells in an allogenic setting. Hence, unlike autologous CAR-T cells, therapeutic CD19-CAR-NK cells can be generated as an off-the-shelf product from healthy donors. Nevertheless, genetic engineering of peripheral blood (PB) derived NK cells remains challenging and optimized protocols are needed. In our study, we aimed to optimize the generation of CD19-CAR-NK cells by retroviral transduction to improve the high antileukemic capacity of NK cells. We compared two different retroviral vector platforms, the lentiviral and alpharetroviral, both in combination with two different transduction enhancers (Retronectin and Vectofusin-1). We further explored different NK cell isolation techniques (NK cell enrichment and CD3/CD19 depletion) to identify the most efficacious methods for genetic engineering of NK cells. Our results demonstrated that transduction of NK cells with RD114-TR pseudotyped retroviral vectors, in combination with Vectofusin-1 was the most efficient method to generate CD19-CAR-NK cells. Retronectin was potent in enhancing lentiviral/VSV-G gene delivery to NK cells but not alpharetroviral/RD114-TR. Furthermore, the Vectofusin-based transduction of NK cells with CD19-CARs delivered by alpharetroviral/RD114-TR and lentiviral/RD114-TR vectors outperformed lentiviral/VSV-G vectors. The final generated CD19-CAR-NK cells displayed superior cytotoxic activity against CD19-expressing target cells when compared to non-transduced NK cells achieving up to 90% specific killing activity. In summary, our findings present the use of RD114-TR pseudotyped retroviral particles in combination with Vectofusin-1 as a successful strategy to genetically modify PB-derived NK cells to achieve highly cytotoxic CD19-CAR-NK cells at high yield.
Dold, Annabelle Cynthia Elisabeth ; Han, Hong ; Liu, Niankun ; Hildebrandt, Andrea ; Brüggemann, Mirko ; Rücklé, Cornelia ; Hänel, Heike ; Busch, Anke ; Beli, Petra ; Zarnack, Katharina ; König, Julian ; Roignant, Jean-Yves ; Lasko, Paul
Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR.
This paper provides an overview of how to use "big data" for economic research. We investigate the performance and ease of use of different Spark applications running on a distributed file system to enable the handling and analysis of data sets which were previously not usable due to their size. More specifically, we explain how to use Spark to (i) explore big data sets which exceed retail grade computers memory size and (ii) run typical econometric tasks including microeconometric, panel data and time series regression models which are prohibitively expensive to evaluate on stand-alone machines. By bridging the gap between the abstract concept of Spark and ready-to-use examples which can easily be altered to suite the researchers need, we provide economists and social scientists more generally with the theory and practice to handle the ever growing datasets available. The ease of reproducing the examples in this paper makes this guide a useful reference for researchers with a limited background in data handling and distributed computing.
The hydrogen-dependent carbon dioxide reductase is a soluble enzyme complex that directly utilizes hydrogen (H2) for the reduction of carbon dioxide (CO2) to formate in the first step of the acetyl-coenzyme A- or Wood-Ljungdahl pathway (WLP). HDCR consists of 2 catalytic subunits, a hydrogenase and a formate dehydrogenase (FDH) and two small subunits carrying iron-sulfur clusters. The enzyme complex has been purified and characterized from two acetogenic bacteria, from the mesophile Acetobacterium woodii and, recently, from the thermophile Thermoanaerobacter kivui. Physiological studies toward the importance of the HDCR for growth and formate metabolism in acetogens have not been carried out yet, due to the lack of genetic tools. Here, we deleted the genes encoding HDCR in T. kivui taking advantage of the recently developed genetic system. As expected, the deletion mutant (strain TKV_MB013) did not grow with formate as single substrate or under autotrophic conditions with H2 + CO2. Surprisingly, the strain did also not grow on any other substrate (sugars, mannitol or pyruvate), except for when formate was added. Concentrated cell suspensions quickly consumed formate in the presence of glucose only. In conclusion, HDCR provides formate which was essential for growth of the T. kivui mutant. Alternatively, extracellularly added formate served as terminal electron acceptor in addition to CO2, complementing the growth deficiency. The results show a tight coupling of multi-carbon substrate oxidation to the WLP. The metabolism in the mutant can be viewed as a coupled formate + CO2 respiration, which may be an ancient metabolic trait.
We introduce Implied Volatility Duration (IVD) as a new measure for the timing of uncertainty resolution, with a high IVD corresponding to late resolution. Portfolio sorts on a large cross-section of stocks indicate that investors demand on average about seven percent return per year as a compensation for a late resolution of uncertainty. In a general equilibrium model, we show that `late' stocks can only have higher expected returns than `early' stocks if the investor exhibits a preference for early resolution of uncertainty. Our empirical analysis thus provides a purely market-based assessment of the timing preferences of the marginal investor.
Hannig, Jennifer ; Schäfer, Hendrik ; Ackermann, Jörg ; Hebel, Marie ; Schäfer, Tim ; Döring, Claudia ; Hartmann, Sylvia ; Hansmann, Martin-Leo ; Koch, Ina
In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significant favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.
Dieser Beitrag betrachtet die Verwendung von Fotografien des Brandenburger Tors in Schulbüchern für die gymnasiale Oberstufe in Hessen. US-Präsident Ronald Reagan machte mit seiner Rede 1987 das Tor zum Symbol der deutschen Teilung:
"Mr. Gorbachev, open this gate! Mr. Gorbachev, tear down this wall!"
Untersucht wird die Frage: Werden Fotografien des Brandenburger Tors vornehmlich im Kontext der deutschen Teilung verwendet?
Yalachkov, Yavor Vasilev ; Uhlmann, Valerie ; Bergmann, Johannes ; Soydaş, Dilara ; Frisch, Stefan ; Behrens, Marion ; Förch, Christian ; Gehrig, Johannes
Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease.
Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established.
Results: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates.
Conclusions: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.
Lyme disease (LD), which is caused by genospecies of the Borrelia burgdorferi sensu lato complex, is the most common vector-borne disease in the Northern hemisphere. Spirochetes are transmitted by Ixodes ticks and maintained in diverse vertebrate animal hosts. Following tick bite, spirochetes initially establish a localized infection in the skin. However, they may also disseminate hematogenously to several distal sites, including heart, joints, or the CNS. Because they need to survive in diverse microenvironments, from tick vector to mammalian hosts, spirochetes have developed multiple strategies to combat the numerous host defense mechanisms. One of these strategies includes the production of a number of complement-regulator acquiring surface proteins (CRASPs) which encompass CspA, CspZ, and OspE paralogs to blunt the complement pathway. These proteins are capable of preventing complement activation on the spirochete surface by binding to complement regulator Factor H. The genes encoding these CRASPs differ in their expression patterns during the tick-to-host infection cycle, implying that these proteins may exhibit different functions during infection. This review summarizes the recent published reports which investigated the roles that each of these molecules plays in conferring tick-borne transmission and dissemination in vertebrate hosts. These findings offer novel mechanistic insights into LD pathobiology and may facilitate the identification of new targets for preventive strategies against Lyme borreliosis.
Am 7. Oktober 2019 starb plötzlich und unerwartet DIETRICH BÜSCHER, der von uns allen DIETER genannt wurde. Er gehörte seit den 1980er Jahren zu den bekanntesten und sicherlich auch emsigsten Botanikern Nordrhein-Westfalens und war im BOCHUMER BOTANISCHEN VEREIN eines der ersten Mitglieder. DIETER erforschte nicht nur jahrzehntelang die Flora des Landes, sondern setzte sich auch aktiv und energisch für den Erhalt der Natur ein. Mit ihm verliert unser Verein und insbesondere auch das Ruhrgebiet einen der besten Kenner der hiesigen Flora und ihrer Veränderungen in den letzten 40 Jahren.
Dass Pflanzenarten bei aller Dynamik nicht einfach zufällig an bestimmten Orten zusammen erscheinen, sondern in wiederkehrenden und beschreibbaren Mustern, ist in der Öffentlichkeit noch immer wenig bekannt. Diese Muster werden von der Vegetationskunde seit ihren Anfängen im 19. Jahrhundert wissenschaftlich untersucht. Die Grundeinheit ist dabei die Pflanzengesellschaft oder Assoziation. Damit ist die Gesamtheit aller Pflanzenarten gemeint, die unter bestimmten biotischen und abiotischen Bedingungen regelhaft miteinander koexistieren. Um auf die Gefährdung und Schutzwürdigkeit der heimischen Pflanzengesellschaften aufmerksam zu machen, hat die Floristisch-Soziologische Arbeitsgemeinschaft (Tuexenia) für das Jahr 2019 zum ersten Mal eine "Pflanzengesellschaft des Jahres" ausgerufen (DIERSCHKE & HEINKEN 2018, TISCHEW & al. 2018). Die Wahl ist auf die Glatthaferwiese (Arrhenatheretum elatioris) gefallen, was kaum ein Zufall sein dürfte, denn Glatthaferwiesen gehören zu den buntesten und auffälligsten Pflanzengesellschaften unserer Landschaften – und sie sind im Flachland mittlerweile von vollständiger Vernichtung bedroht (FINCK & al. 2017).
Es wird über einen Fund von Alyxoria ochrocheila an Fraxinus excelsior in Nordrhein-Westfalen bei Hirschrott im Naturschutzgebiet "Erkensruhrtal mit Nebenbächen und Felsen am Oberseeufer" im Nationalpark Eifel berichtet, der einen Neufund für die Nordeifel und den Nationalpark Eifel darstellt. Die Neuansiedlung steht wahrscheinlich im Zusammenhang mit den steigenden Temperaturen im Rahmen des Klimawandels.
Auf einer etwa 0,5 ha großen Obstwiese an der Schattbachstraße in Bochum-Querenburg/Laer wurden von Mai 2018 bis Juli 2019 Flora, Fauna und Funga soweit möglich erfasst. Die Artenliste soll als Grundlage dienen, Veränderungen in der Artenzahl und Artenzusammensetzung bei einer späteren Untersuchung analysieren zu können. Diese Veränderungen erfolgen durch die Überführung der ehemaligen Wiesenbrache mit gelegentlicher Beweidung in eine zweischürige Glatthaferwiese im Sinn einer "Historischen Wiese". Insgesamt wurden 710 Arten nachgewiesen, unter ihnen 183 Pflanzenarten (168 Gefäßpflanzen, 13 Moose, 2 Algen), 32 Pilzarten, 13 Flechtenarten und 482 Tierarten. Bei den Tieren stand die Erfassung der Insekten (400 Arten), insbesondere der Anteil der Bestäuber (158 Arten, 40 %), im Fokus. Durch die Nutzungsänderung zu einer blütenreichen Mähwiese sind in dieser Gruppe am ehesten positive Veränderungen zu erwarten. Die Bestäuber werden hinsichtlich ihrer Blütenbesuche analysiert und die wichtigsten Pflanzenarten aufgeführt, an denen sie beobachtet wurden. Dabei stellen sich neben den Obstbäumen fünf Arten der Krautschicht (Senecio jacobaea, Heracleum sphondylium, Daucus carota, Anthriscus sylvestris und Cirsium arvense) mit jeweils 20 oder mehr unterschiedlichen Bestäubern als meistbesuchte Arten heraus. Bei der Bestäubung dominieren mit 38 % Hautflügler-Arten (Hymenoptera), gefolgt von Zweiflüglern (Diptera, 26 %), Käfern (Coleoptera, 18 %) und Schmetterlingen (Lepidoptera, 18 %). Die Anteile der gefährdeten Arten mit 9 (1,7 %) (zusätzlich 9 Arten der Vorwarnliste) und der Neobiota mit 32 Arten (4,5 %, 19 Neophyten, davon 10 unbeständig, und 13 Tierarten) sind relativ gering. Die gewählten Entwicklungsmaßnahmen der Wiese, die neben der Mahd auch Einsaaten umfassen, werden erläutert und Artenzahlen sowie Erfolgsperspektiven auch vor dem Hintergrund der klimatischen Änderungen diskutiert.
Als Maßnahme gegen das "Insektensterben" werden Samentütchen im Handel angeboten oder von Firmen und Behörden verteilt, die im Garten, aber auch in der freien Landschaft, ausgestreut werden. Häufig wird dies von Naturschutzverbänden unterstützt. Der Inhalt dieser Tütchen ist in der Regel nicht dokumentiert und besteht in vielen Fällen aus nicht-einheimischen, einjährigen Arten, die zu keinem nachhaltigen, positiven Effekt in der Natur führen und höchstens den häufigen Insektenarten nützen. Es werden die Komplexität der Themenfelder "Insek-tensterben" und "Ansaaten" beleuchtet und Handlungsalternativen zur ungezielten Samenaussaat aufgezeigt.
Ein kleiner Bestand von Ranunculus parviflorus konnte im Mai 2019 erstmals für Nordrhein-Westfalen in einem lückigen Scherrasen auf dem Friedhof in Zülpich-Juntersdorf/Kreis Euskirchen nachgewiesen werden. Das Vorkommen in Juntersdorf sowie die Merkmale, Verbreitung und Ökologie der mediterran-atlantischen Art werden diskutiert.
Am Ufer der Rurtalsperre (Untersee) konnten im Frühherbst 2018 größere Bestände von Cardamine occulta beobachtet werden. Es handelt sich um den zweiten Nachweis an einem naturnahen Standort in Nordrhein-Westfalen. Die Ökologie und Phänologie der neophytischen Art werden diskutiert. Bisher wurden in Europa außer an Ufern des Bodensees und des Rheins sowie in Reisfeldern in Norditalien nur Vorkommen in stark anthropogen beeinflussten Lebensräumen, wie Gärtnereien, Blumenkübeln und Friedhöfen beobachtet. Es lassen sich zwei Hauptentwicklungsphasen im Spätwinter/Frühjahr und im Spätsommer/Herbst feststellen. Während an anthropogenen Standorten wie Friedhöfen zu beiden Zeiten blühende Pflanzen beobachtet werden können, beschränken sich die Vorkommen an natürlichen/naturnahen Standorten offenbar entweder wie am Bodensee auf das Winter- oder wie in Nordrhein-Westfalen auf das Sommerhalbjahr.
Die Variabilität der häufigen Arten Sonchus asper und S. oleraceus in Aachen wird dargestellt, und ihre Unter-scheidungsmerkmale werden kritisch diskutiert. Sie bereiten häufiger Bestimmungsprobleme als erwähnt wird, da viele Merkmale stark variieren und zumindest bei einzelnen Pflanzen ausfallen können. Zuverlässig ist in Zwei-felsfällen die Fruchtoberfläche. Die auffallende Variabilität beider Arten wird oft als rein modifikativ oder taxono-misch unbedeutend abgetan. Bei beiden Arten gibt es aber beachtenswerte Sippen: Bei S. asper sind zwei in der Blattteilung extreme Sippen weitgehend konstant und einheitlich, es gibt aber eine Zwischensippe, die möglich-erweise ebenfalls eigenständig ist. Neben einer häufigen typischen Sippe von S. oleraceus und selteneren Lokal-sippen lässt sich eine feinblättrige Sippe als mögliche Art S. reversus abtrennen. Gerade bei S. oleraceus stellt sich vielfach die Frage, ob Merkmale oder gar manche Sippen insgesamt auf Introgression von S. asper beruhen.
Hypericum perforatum s. str. und morphologisch ähnliche Hybriden (H. ×desetangsii s. l.) werden als Sammel-arten aufgefasst, die jeweils mehrere eng umgrenzte Arten umfassen. Beide Artengruppen werden im Aachener Raum unterschieden anhand strichförmiger dunkler Öldrüsen an der Außenseite der Kronblätter, die H. perforatum s. str. fehlen und bei Hybriden vorhanden sind. Andere morphologische Merkmale und besonders die Ökologie sind ebenfalls Unterschiede beider Gruppen. Ihre Umgrenzung und ihre Entstehung werden disku-tiert. Eine Sippe, die der Verfasser als eine H. perforatum nahestehende Hybride auffasst, wird als neue, hybrido-gene Art H. patzkei zu Ehren des verstorbenen Prof. Dr. ERWIN PATZKE beschrieben, der sie als erster als phäno-logisch und morphologisch abweichendes Taxon erkannt hat. H. patzkei beginnt früh mit der Blüte und kann u. a. anhand schmaler Blätter mit wenigen hellen Öldrüsen, dunklen strichförmigen Öldrüsen an der Außenseite der Kronblätter und einem schmalen Habitus mit spitzwinklig abstehenden Seitenästen unterschieden werden. Die Art ist charakteristischer für offene Stellen in Wäldern und deren Ränder als für trockene, offene Lebensräume, ist aber ökologisch ziemlich variabel. Sie ist bisher bekannt in der Umgebung von Aachen und nahe gelegenen Stellen in Belgien.
Im Folgenden werden für das östliche Ruhrgebiet bemerkenswerte Funde aufgeführt. Das Gebiet umfasst die Städte Gelsenkirchen, Essen, Herne, Bochum, Dortmund, Hagen und Hamm sowie die Kreise Recklinghausen, Unna und den Ennepe-Ruhr-Kreis. Zur besseren Auswertung sind hinter den Fundorten die MTB-Angaben (Topographische Karte 1:25000) und ggf. eine Bewertung des Fundes für den hiesigen Raum und der floristische Status hinzugefügt. Funde aus dem östlichen Ruhrgebiet, die von nordrhein-westfälischer Bedeutung sind, sind im Beitrag BOCHUMER BOTANISCHER VEREIN (2020) aufgeführt. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach PAROLLY & ROHWER (2016).
Hier werden bemerkenswerte floristische Funde aus Nordrhein-Westfalen aus dem Jahr 2019 und einige Nachträge aus 2018 zusammengestellt, die aus Sicht der Schriftleitung von landesweiter Bedeutung sind. Die Funde werden im Laufe des Jahres zunächst chronologisch auf die Homepage des BOCHUMER BOTANISCHEN VEREINS gestellt und am Ende des Jahres zu einem Artikel zusammengefasst. Bei der Auswahl der Arten für diese Liste ist nicht an Bestätigung bereits lange bekannter Vorkommen gedacht, die an Ort und Stelle durchgehend vorkommen, sondern z. B. an Neufunde seltener Arten, Wiederfunde seltener Arten, die zwischendurch verschwunden schienen (wie z. B. Ackerunkräuter) oder auch an bekannte Vorkommen, die erloschen sind oder kurz vor dem Erlöschen stehen. Außerdem nehmen Beobachtungen von neophytischen Arten einen großen Raum ein, die entweder auf dem Wege der Einbürgerung sind, deren Einbürgerung noch nicht allgemein bekannt bzw. anerkannt ist oder deren Vorkommen bisher erst selten für Nordrhein-Westfalen veröffentlicht wurden. Ein wichtiges Kriterium für aufgeführte Arten ist die Selten-heit im Bundesland oder der betreffenden Großlandschaft bzw. Region. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach PAROLLY & ROHWER 2016.
Linguistic research and linguistic activism have resulted in key changes to official language use. However, revisions remain contested and many English and German speakers continue to employ male generic terms. In this article I explore whether the encounter with sex-/gender-neutral terminology in June Arnold's novel 'The Cook and the Carpenter' can prompt readers to review their language use and consider alternatives. Based on narrative research, my premise is that fiction can create familiarity with new terms, which is the first step toward wider linguistic change. I frame my investigation with Wittgenstein's notion that "to imagine a language means to imagine a form of life", and put it to the test with a discourse analysis of English and German reader responses. The results of my study show that Arnold's novel stimulates fruitful debate around the issue of linguistic representation. Based on my findings, I propose to integrate literary texts which engage with the issue of sex/gender and language into educational settings to further promote neutral/inclusive language use.
Uni-Highlights Februar 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
Marwitz, Sebastian ; Turkowski, Kati ; Nitschkowski, Dörte ; Weigert, Andreas ; Brandenburg, Julius ; Reiling, Norbert ; Thomas, Michael ; Reck, Martin ; Drömann, Daniel ; Seeger, Werner ; Rabe, Klaus F. ; Savai, Rajkumar ; Goldmann, Torsten
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.
The dynamic and reversible post-translational modification of proteins and protein complexes with the ubiquitin-related SUMO modifier regulates a wide variety of nuclear functions, such as transcription, replication and DNA repair. SUMO can be attached as a monomer to its targets, but can also form polymeric SUMO chains. While monoSUMOylation is generally involved in the assembly of protein complexes, multi- or polySUMOylation may have very different consequences. The evolutionary conserved paradigmatic signaling process initiated by multi- or polySUMOylation is the SUMO-targeted Ubiquitin ligase (StUbL) pathway, where the presence of multiple SUMO moieties primes ubiquitylation by the mammalian E3 ubiquitin ligases RNF4 or RNF111, or the yeast Slx5/8 heterodimer. The mammalian SUMO chain-specific isopeptidases SENP6 or SENP7, or yeast Ulp2, counterbalance chain formation thereby limiting StUbL activity. Many facets of SUMO chain signaling are still incompletely understood, mainly because only a limited number of polySUMOylated substrates have been identified. Here we summarize recent work that revealed a highly interconnected network of candidate polySUMO modified proteins functioning in DNA damage response and chromatin organization. Based on these datasets and published work on distinct polySUMO-regulated processes we discuss overarching concepts in SUMO chain function. We propose an evolutionary conserved role of polySUMOylation in orchestrating chromatin dynamics and genome stability networks by balancing chromatin-residency of protein complexes. This concept will be exemplified in processes, such as centromere/kinetochore organization, sister chromatid cohesion, DNA repair and replication.
Ehrenmord : ein Phänomen zwischen Obskurantismus, Angst und wirtschaftlichem Kalkül : ein Essay
(2020)
Ehrenmord ist ein komplexes Phänomen, in dem sich diverse psychologische, historische, religiöse, ethnologische, juristische, wirtschaftliche und soziologische Vorstellungen und Interessen explosiv aufeinandertreffen. Um die Ehrenmordmotive zu verstehen, sollten die Menge der Faktoren und Beweggründe differenziert und jedes der Motive sowohl einzeln als auch im Zusammenwirken betrachtet werden. Generell sind herbei zwei Aspekte besonders hervorzuheben: verdrängte sozial-tabuisierte Sexualität einerseits und wirtschaftlicher Kalkül andererseits. Die islamischen Inhalte begründen zwar Ehrenmord nicht direkt, untermauern aber an einigen Punkten konservative Vorstellungen innerhalb der Stammesmentalität, die zu einem Ehrenmord als logisch erscheinende Konsequenz führen können. Voraussetzung dafür ist jedoch eine extrem konservative Leseart der islamischen Quellen.
Suicide represents a major challenge to public mental health. In order to provide empirical evidence for prevention strategies, we hypothesized current levels of low socioeconomic status (SES) and high social isolation (SI) to be linked to increased suicide rates in N = 390 administrative districts since SES and SI are associated with mental illness. Effects of SES on suicide rates were further expected to be especially pronounced in districts with individuals showing high SI levels as SI reduces the reception of social support and moderates the impact of low SES on poor mental health. We linked German Microcensus data to register data on all 149,033 German suicides between 1997 and 2010 and estimated Prentice and Sheppard’s model for aggregate data to test the hypotheses, accounting for spatial effect correlations. The findings reveal increases in district suicide rates by 1.20% (p < 0.035) for 1% increases of district unemployment, suicide rate decreases of −0.39% (p < 0.028) for 1% increases in incomes, increases of 1.65% (p < 0.033) in suicides for 1% increases in one-person-households and increases in suicide rates of 0.54% (p < 0.036) for 1% decreases in single persons’ incomes as well as suicide rate increases of 3.52% (p < 0.000) for 1% increases in CASMIN scores of individuals who moved throughout the year preceding suicide. The results represent appropriate starting points for the development of suicide prevention strategies. For the definition of more precise measures, future work should focus on the causal mechanisms resulting in suicidality incorporating individual level data.
We study the incidence and severity of lower-bound episodes and the efficacy of three types of state-dependent policies—forward guidance about the future path of interest rates, large-scale asset purchases and spending-based fiscal stimulus—in ameliorating the adverse consequences stemming from the effective lower bound on nominal interest rates. In particular, we focus on the euro area economy and examine, using the ECB’s New Area- Wide Model, the consequences of the lower bound both for the near-term economic outlook, characterised by persistently low nominal interest rates and inflation, and in a lasting low-real-interest-rate world. Our findings suggest that, if unaddressed, the lower bound can have very substantial costs in terms of worsened macroeconomic performance. Forward guidance, if fully credible, is most powerful and can largely undo the distortionary effects due to the lower bound. A combination of imperfectly credible forward guidance, asset purchases and fiscal stimulus is almost equally effective, in particular when asset purchases enhance the credibility of the forward guidance policy via a signalling effect.
Study design: Systematic review with meta-analysis and meta-regression.
Background and objectives: We systematically reviewed and delineated the existing evidence on sustainability effects of motor control exercises on pain intensity and disability in chronic low back pain patients when compared with an inactive or passive control group or with other exercises. Secondary aims were to reveal whether moderating factors like the time after intervention completion, the study quality, and the training characteristics affect the potential sustainability effects.
Methods: Relevant scientific databases (Medline, Web of Knowledge, Cochrane) were screened. Eligibility criteria for selecting studies: All RCTs und CTs on chronic (≥ 12/13 weeks) nonspecific low back pain, written in English or German and adopting a longitudinal core-specific/stabilizing sensorimotor control exercise intervention with at least one pain intensity and disability outcome assessment at a follow-up (sustainability) timepoint of ≥ 4 weeks after exercise intervention completion.
Results and conclusions: From the 3,415 studies that were initially retrieved, 10 (2 CTs & 8 RCTs) on N = 1081 patients were included in the review and analyses. Low to moderate quality evidence shows a sustainable positive effect of motor control exercise on pain (SMD = -.46, Z = 2.9, p < .001) and disability (SMD = -.44, Z = 2.5, p < .001) in low back pain patients when compared to any control. The subgroups’ effects are less conclusive and no clear direction of the sustainability effect at short versus mid versus long-term, of the type of the comparator, or of the dose of the training is given. Low quality studies overestimated the effect of motor control exercises.