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Ubiquitination regulates nearly all cellular processes by coordinated activity of ubiquitin writers (E1, E2, and E3 enzymes), erasers (deubiquitinating enzymes) and readers (proteins that recognize ubiquitinated proteins by their ubiquitin-binding domains). By differentially modifying cellular proteome and by recognizing these ubiquitin modifications, ubiquitination machinery tightly regulates execution of specific cellular events in space and time. Dynamic and complex ubiquitin architecture, ranging from monoubiquitination, multiple monoubiquitination, eight different modes of homotypic and numerous types of heterogeneous polyubiquitin linkages, enables highly dynamic and complex regulation of cellular processes. We discuss available tools and approaches to study ubiquitin networks, including methods for the identification and quantification of ubiquitin-modified substrates, as well as approaches to quantify the length, abundance, linkage type and architecture of different ubiquitin chains. Furthermore, we also summarize the available approaches for the discovery of novel ubiquitin readers and ubiquitin-binding domains, as well as approaches to monitor and visualize activity of ubiquitin conjugation and deconjugation machineries. We also discuss benefits, drawbacks and limitations of available techniques, as well as what is still needed for detailed spatiotemporal dissection of cellular ubiquitination networks
Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts
(2020)
Induction of autophagy can have beneficial effects in several human diseases, e.g. cancer and neurodegenerative diseases (ND). Here, we therefore evaluated the potential of two novel autophagy-inducing compounds, i.e. STF-62247 and pimozide, to stimulate autophagy as well as autophagic cell death (ACD) using mouse embryonic fibroblasts (MEFs) as a cellular model. Importantly, both STF-62247 and pimozide triggered several hallmarks of autophagy in MEFs, i.e. enhanced levels of LC3B-II protein, its accumulation at distinct cytosolic sites and increase of the autophagic flux. Intriguingly, autophagy induction by STF-62247 and pimozide resulted in cell death that was significantly reduced in ATG5- or ATG7-deficient MEFs. Consistent with ACD induction, pharmacological inhibitors of apoptosis, necroptosis or ferroptosis failed to protect MEFs from STF-62247- or pimozide-triggered cell death. Interestingly, at subtoxic concentrations, pimozide stimulated fragmentation of the mitochondrial network, degradation of mitochondrial proteins (i.e. mitofusin-2 and cytochrome c oxidase IV (COXIV)) as well as a decrease of the mitochondrial mass, indicative of autophagic degradation of mitochondria by pimozide. In conclusion, this study provides novel insights into the induction of selective autophagy as well as ACD by STF-62247 and pimozide in MEFs.
One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig’s blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.
Finding subgroups in biomedical data is a key task in biomedical research and precision medicine. Already one-dimensional data, such as many different readouts from cell experiments, preclinical or human laboratory experiments or clinical signs, often reveal a more complex distribution than a single mode. Gaussian mixtures play an important role in the multimodal distribution of one-dimensional data. However, although fitting of Gaussian mixture models (GMM) is often aimed at obtaining the separate modes composing the mixture, current technical implementations, often using the Expectation Maximization (EM) algorithm, are not optimized for this task. This occasionally results in poorly separated modes that are unsuitable for determining a distinguishable group structure in the data. Here, we introduce “Distribution Optimization” an evolutionary algorithm to GMM fitting that uses an adjustable error function that is based on chi-square statistics and the probability density. The algorithm can be directly targeted at the separation of the modes of the mixture by employing additional criterion for the degree by which single modes overlap. The obtained GMM fits were comparable with those obtained with classical EM based fits, except for data sets where the EM algorithm produced unsatisfactory results with overlapping Gaussian modes. There, the proposed algorithm successfully separated the modes, providing a basis for meaningful group separation while fitting the data satisfactorily. Through its optimization toward mode separation, the evolutionary algorithm proofed particularly suitable basis for group separation in multimodally distributed data, outperforming alternative EM based methods.
Background: High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model.
Results: Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F.
Conclusions: D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.
Though the range of invariance in recognition of novel objects is a basic aspect of human vision, its characterization has remained surprisingly elusive. Here we report tolerance to scale and position changes in one-shot learning by measuring recognition accuracy of Korean letters presented in a flash to non-Korean subjects who had no previous experience with Korean letters. We found that humans have significant scale-invariance after only a single exposure to a novel object. The range of translation-invariance is limited, depending on the size and position of presented objects. To understand the underlying brain computation associated with the invariance properties, we compared experimental data with computational modeling results. Our results suggest that to explain invariant recognition of objects by humans, neural network models should explicitly incorporate built-in scale-invariance, by encoding different scale channels as well as eccentricity-dependent representations captured by neurons’ receptive field sizes and sampling density that change with eccentricity. Our psychophysical experiments and related simulations strongly suggest that the human visual system uses a computational strategy that differs in some key aspects from current deep learning architectures, being more data efficient and relying more critically on eye-movements.
Eine junge schwarze Frau lässt sich in einem mehrstündigen Prozess vor den Augen der Zuschauer*innen ihr krauses Afrohaar glätten, dann schüttet sie einen Eimer Wasser über ihr Haupt – die Performance "El tanque" der afrokubanischen Künstlerin Susana Pilar Delahante Matienzi in der neuen Werk-Kolumne "Kurz vorgestellt".
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!
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.
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.
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.
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.
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.
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?
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.
Uni-Highlights Februar 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
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.
Endothelial dysfunction plays an important role in different pathological conditions, but whether endothelial cell death contributes to the development and progression of certain pathological conditions is rather unclear. Here we found that endothelial cells undergo cell death during pathologies such as LPS-induced sepsis and in models of hindlimb, renal and cardiac ischemia-reperfusion injury. Analyses of mice lacking endothelial key cell death regulators such as TAK1, RIPK3 and Caspase 8 gave us insight in the role of endothelial cell death in these pathological models. For example, increased endothelial necroptosis along with basal inflammation in lungs of TAK1ECKO mice affects susceptibility to LPS-induced sepsis and mortality, which correlated with elevated IFN-gamma and MIP-2 serum levels. Furthermore, we found that inhibition of RIPK3-mediated endothelial necroptosis could reduce the susceptibility of TAK1ECKO mice to LPS-induced sepsis and mortality. In ischemia or ischemia-reperfusion models, inhibition of RIPK3-mediated endothelial necroptosis did not reduce injury in the heart after ischemia, nor did it have any effect on organ function post-injury in the kidney or the heart. Inhibition of necroptosis also did not alter vascularization processes in hindlimb post-ischemia. Taken together, endothelial necroptosis contributes to increased sepsis severity and progression whereas inhibition of endothelial necroptosis can ameliorate susceptibility to sepsis in the absence of endothelial TAK1. Inhibition of endothelial necroptosis however does not play an important role during ischemia or ischemia-reperfusion induced organ injury.
Die Disposition des anzuzeigenden Buches lässt sich auf folgende Kurzformel bringen: drei antike Historiographen und zwei schlechte Kaiser. Indessen, wie schreibt man als antiker Autor über einen der damnatio memoriae verfallenen Kaiser, wenn ihn (1.) seine Zeitgenossen positiv oder zumindest neutral darstellten, man (2.) gleichzeitig auf eine panegyrische Überlieferung zurückgreifen musste, die von der Angst vor Sanktionen gekennzeichnet war, und (3.) man seinem eigenen Publikum gefallen mochte? Ziel des Buches ist nicht etwa die Rekonstruktion historischer Realität, oder die retrospektive Diagnose des vom Friedensnobelpreisträger Ludwig Quidde unterstellten Caesarenwahnsinns, sondern die Analyse der literarischen Strategien römischer Historiker und Biographen zur Konstruktion eines negativen (und bis heute wirksamen) Herrscherbildes von Nero und Domitian. Damit wird von Anfang an der Weg bezeichnet, auf dem vorangeschritten werden soll: Es ist eher der eines Hayden White und nicht der eines Ronald Syme. ...
Bange zeigt mit seiner Studie zum römischen Kreditgeldwesen auf, dass bereits lange vor dem 13. Jahrhundert – so die ‚klassische‘ Einschätzung für das Aufkommen eines modernen Bankwesens – ein Kreditgeldsystem verwendet wurde, und unterstützt eine modernistische Deutung der römischen Wirtschaftsgeschichte. In der Einleitung (S. 14) wendet er sich gegen die negativen Ansichten von Moses I. Finley und steht dabei in mancher Weise in einer Tradition mit anderen geldwirtschaftlichen Forschungsbeiträgen, so etwa mit Sitta von Redens wichtiger Monographie "Money in Classical Antiquity", wobei die schematische bipolare Wahrnehmung primitivistischer oder modernistischer Ansätze an sich in weiten Teilen der aktuellen Wirtschaftsgeschichte als überholt anzusehen ist. Ferner beklagt Bange, dass gerade die numismatische Forschung eine lediglich verengte, letztlich in Übereinstimmung mit Finley vereinfachte "Geld gleich Münze"-Perspektive eingenommen hätte (S. 15). Diese Einschätzung, die sich auf die positivistische Material- bzw. Grundlagenarbeit der Numismatik fokussiert und mit einem Zitat aus Francesco de Martinos Klassiker "Wirtschaftsgeschichte des alten Rom" (1991) unterlegt wird, erscheint als Kritik an numismatischen Beiträgen zur antiken Wirtschaftsgeschichte zu absolut und verallgemeinernd formuliert. ...
Im Verlauf einer Erkundungsexpedition des britischen Militärs in Ägypten wurde 1917 in der Westwüste zwischen der Oase Dachla und dem Gilf Kebir an der Grenze zu Libyen und dem Sudan von dem mitreisenden britischen Geologen und Geographen Jon Ball am Fuße einer von zwei weithin sichtbaren Geländeerhebungen aus Sandstein eine größere Anzahl von Gefäßen bzw. Gefäßresten aus Ton entdeckt. Ball bezeichnete die nördliche der beiden Erhebungen mit einer Höhe von ca. 39 m der vielen Gefäßfunde wegen als Pottery Hill. Die heutige Bezeichnung ist der arabische Name Abu Ballas. Die Entfernung zur Oase Dachla beträgt etwa 200 km. Die Geländeerhebungen waren zunächst nur als geographische Fixpunkte in der sonst ebenen Wüste von Interesse. ...
In jüngeren geschichtswissenschaftlichen Arbeiten über die römische Kaiserzeit ist ein wiederentdecktes Interesse an den vermeintlich "schlechten" Kaisern unverkennbar. Zu den umstrittensten principes des 1. Jahrhunderts n.Chr. zählt auch Domitian, der letzte Flavier auf dem Herrscherthron, der von der zeitgenössischen Literatur zum Iuppiter-gleichen Idealherrscher stilisiert, in den nach seiner Ermordung erschienenen Schriften dagegen als Tyrann gebrandmarkt wurde. ...
Die in der renommierten Reihe der Göttinger Orientforschungen erschienene Arbeit ist einem Thema gewidmet, das in der ägyptologischen Forschung trotz seiner offenkundig hohen Relevanz und Bedeutung lange Zeit ziemlich vernachlässigt wurde: dem vielschichtigen und facettenreichen Phänomen des Reisens im Alten Ägypten. Wie dem Untertitel zu entnehmen ist, werden dabei neben einer Vielzahl von relevanten, unter dem weiten Begriffsfeld "Reisekultur" subsumierten Aspekten insbesondere praktische Fragen nach den Fortbewegungs- und Transportmitteln in pharaonischer Zeit in den Vordergrund gestellt, doch kommt das Spektrum der textlich belegten individuellen Reisenden selbst und ihrer verschiedenen Motivationen und Destinationen keineswegs zu kurz. In der Tat kann das schmale Niltal als langgestreckte Flussoase mitsamt den unmittelbar angrenzenden Wüstengebieten in Ost und West einerseits und dem breiten, von zahlreichen Kanälen und Verbindungswegen durchzogenen Nildelta im Norden andererseits als eine naturräumlich besonders "verkehrsträchtige" Region gelten, die durch die landschaftlichen Gegebenheiten besondere Möglichkeiten bot, aber auch spezielle, nicht zuletzt verkehrstechnische und logistische Anforderungen an Reisen und Reisende in pharaonischer Zeit stellte – vor allem, wenn das Reiseziel außerhalb der eigenen kulturellen Grenzen lag. Zudem erlaubt das außerordentlich lange Bestehen der pharaonischen Hochkultur im Verbund mit einer relativ reichen Quellenlage kulturhistorisch aufschlussreiche diachrone Betrachtungen, etwa im Hinblick auf die Entwicklung von Reise- und Transportmitteln, den Ausbau des Verkehrs- und Wegesystems oder allgemeine sozio-ökonomische Prozesse, die mit Fragen der Mobilität zusammenhängen. ...
Das Geschichtswerk des Florus findet in der modernen althistorischen Forschung nur wenig Anerkennung. Dies geschieht nicht ohne Grund, entspringen doch manche Berichte allzu deutlich der Phantasie des Historiographen und basieren auf einer auf Effekte abzielenden Darstellungskunst. Ein Beispiel hierfür liefert seine Schilderung des Ablaufs der clades Variana, die – beim Wort genommen – kein Vertrauen verdient und daher zumeist in der aktuellen Diskussion über die Vorgänge in Germanien übergangen wird. Dagegen ist Florus anerkanntermaßen ein wichtiger Repräsentant für die Geschichtsschreibung des 2. und 3. Jahrhunderts n. Chr. Der Beitrag zielt nicht darauf ab, das viel diskutierte Problem der ‚Varusschlacht‘ und ihre Lokalisierung erneut zu traktieren, vielmehr sollen neben dem Geschichtsbild des Autors und seiner Auffassung über die den geschichtlichen Prozess beeinflussenden Kräfte die Zeitbezüge verdeutlicht werden, die hinter dem Berichteten als solchem erkennbar sind. Damit gewährt das Werk interessante Einblicke in Erwartungen, Vorstellungen und Mentalitäten der Zeitgenossen des Autors, was jenseits positivistischer Vermittlung von Fakten auch für den Historiker von Bedeutung ist.
Seit der Mitte des 18. Jahrhunderts ist ein Steinensemble aus Frankfurt-Heddernheim/Nida bekannt, das aus einer 107 cm hohen Geniusstatue und einer zugehörigen Basis (Höhe 54 cm – Breite 50,5 cm – Tiefe 34,5 cm) aus Sandstein besteht. Die im Sockel eingeschlagene Inschrift datiert das Objekt durch die Angabe der amtierenden Konsuln in das Jahr 230 n. Chr. ...
Die Gallia Narbonensis gilt als eine der am stärksten romanisierten Provinzen des Imperium Romanum. Gefördert wurde dieser Umstand sicherlich durch die Nähe zu Italien und die recht frühe Provinzialisierung des Gebietes seit dem 2. Jhdt. v. Chr.1 Dabei wurde in der Forschung oft die Frage gestellt, ob ebenso die Agrarstrukturen Italiens, sprich eine auf Sklavenarbeit beruhende Großvillenwirtschaft, in der Narbonensis etabliert wurden. Trotz des eigentlich spärlichen Quellenmaterials ist die Antwort überraschenderweise meistens positiv. Das Ziel dieses Artikels besteht nun darin, diese Aussagen einer kritischen Prüfung zu unterziehen. Hierzu werden insbesondere Inschriften zur Klärung des Sozialstatus der landwirtschaftlichen Arbeitskräfte herangezogen. Ein kurzer Vergleich mit einigen epigraphischen Belegen aus den benachbarten Provinzen und eine Prüfung der Aussagefähigkeit weiterer Quellen, darunter archäologischer und ikonographischer Zeugnisse, soll die Analyse abrunden.
Seit dem 1. Januar 2018 erhalten alle aktiven Beamt*innen, Richter*innen, Tarifbeschäftigte und Auszubildende des Landes Hessen eine Freifahrtberechtigung, sodass sie den öffentlichen Personennah- und Regionalverkehr im gesamten Bundesland kostenlos nutzen können.
Diese Umstellung stellt den aktuellen Anlass für eine Fallstudie zum Thema Verkehrshandeln am Beispiel der Beschäftigten der Goethe-Universität Frankfurt a.M. dar. Im Frühjahr 2019 wurde eine quantitative Online-Befragung an der Goethe-Universität durchgeführt (n=1686). Als Grundlage und Vergleichsdatensatz diente eine Studie, die im Jahr 2015 an der Gothe-Universität durchgeführt worden ist.
Ziel der Befragung war es, Informationen über die Verkehrsmittelnutzung sowie die Einstellungen zu unterschiedlichen Mobilitätsangeboten zu erhalten. Der Schwerpunkt der Befragung lag dabei auf der Nutzung des hessischen Landestickets.
Das folgende Arbeitspapier befasst sich mit der Methodik der Online-Befragung und dokumentiert das Vorgehen von der Fragebogenerstellung, die Stichprobenauswahl, über die Durchführung bis zur Datenaufbereitung und reflektiert die Repräsentativität der Daten.
To date, there is insufficient insight into inflammatory bowel disease (IBD)-associated stress, recognized disability, and contact with the social care system. We aimed to assess these parameters in IBD patients and a non-IBD control group, who were invited to participate in an online survey developed specifically for this study (www.soscisurvey.de) with the help of IBD patients. 505 IBD patients and 166 volunteers (i.e., control group) participated in the survey. IBD patients reported significantly increased levels of stress within the last six months and five years (p<0.0001) and were more likely to have a recognized disability (p<0.0001). A low academic status was the strongest indicator of a disability (p = 0.006). Only 153 IBD patients (30.3%) reported contact with the social care system, and a disability was the strongest indicator for this (p<0.0001). Our study provides data on stress and disability in a large unselected German IBD cohort. We showed that patients with IBD suffer more often from emotional stress and more often have a recognized disability. As only about 1/3 of the patients had come into contact with the social care system and the corresponding support, this patient group is undersupplied in this area.