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The study of hypernuclei in relativistic ion collisions open new opportunities for nuclear and particle physics. The main processes leading to the production of hypernuclei in these reactions are the disintegration of large excited hyper-residues (target- and projectile-like), and the coalescence of hyperons with other baryons into light clusters. We use the transport, coalescence and statistical models to describe the whole reaction, and demonstrate the effectiveness of this approach: These reactions lead to the abundant production of multi-strange nuclei and new hypernuclear states. A broad distribution of predicted hypernuclei in masses and isospin allows for investigating properties of exotic hypernuclei, as well as the hypermatter both at high and low temperatures. There is a saturation of the hypernuclei production at high energies, therefore, the optimal way to pursue this experimental research is to use the accelerator facilities of intermediate energies, like FAIR (Darmstadt) and NICA (Dubna).
In poet and artist Elena Botts new poetry collection: epochs of morning light, we see a shimmering, variegated new voice; we hear: where the trees still talk to each other, and winter feels like a song... (from When I have died we will be here). We feel the weather of her emotions; a contract with the ethereal and the visceral, as when we stand within the short but large poem: blossoms back to under the earth: I felt your ghost move through me out past the Baltic as though you had been in my heart the whole time. In this sensual canvas, beauty never suffers from loneliness, nor the sublime. Each poem herein as Botts wanders memory and weaves tapestries of word worlds, reveals a true and original voice in modern poetry: allowing light to conquer darkness; darkness to defy the estate of the sun, and colors mixed in ways only an artist of the pen could fathom
The current discussion about a “risk culture” in financial services was triggered by the recent series of financial crises. The last decade saw a long list of hubris, misconduct and criminal activities by human beings on a single or even a collective basis in banks, in the industry or in the whole economy. As a counter-reaction, financial authorities called for a guidance by a “new” risk culture in financial institutions based on a set of abstract, formal, and normative governance processes. While traditional risk research in economics and in banking was focused on the statistical aspects of risk as the probability of loss multiplied by the amount of loss, culture is a paraphrase for the behavior in collectives and dynamics of organization found in human societies. Therefore, a “risk culture” should link the normative concepts of risk with the positive “real-world” decision-making in financial services. This paper will describe a novel view on “risk culture” from the perspective of human beings interacting in dynamical and intertemporal commercial relations. In this context “risk” is perceived by economic agents ex−ante as the consequence of the time lag between the present and the uncertain future development (compared to a probability distribution calculated by observers ex−post). For all those individual decisions—to be made under uncertainty—future “risk” includes the so-called “normal accidents”, i.e., failures that will happen at some uncertain point in time but are inevitable, and the only questions are when failure will happen and how to maintain function in the first line of defense. Finally, the shift from an abstract definition of “risk” as a probability distribution to a role model of “honorable merchants” as a benchmark for significant individual decision-making with individual responsibilities for the uncertain future outcome provides a new framework to discuss the responsibilities in the financial industry.
Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.
The contribution of upper body movements to dynamic balance regulation during challenged locomotion
(2018)
Recent studies suggest that in addition to movements between ankle and hip joints, movements of the upper body, in particular of the arms, also significantly contribute to postural control. In line with these suggestions, we analyzed regulatory movements of upper and lower body joints supporting dynamic balance regulation during challenged locomotion. The participants walked over three beams of varying width and under three different verbally conveyed restrictions of arm posture, to control the potential influence of arm movements on the performance: The participants walked with their arms stretched out perpendicularly in the frontal plane, spontaneously, i.e., without restrictions to the arm movements, and with their hands on their thighs. After applying an inverse-dynamics analysis to the measured joint kinematics, we investigated the contribution of upper and lower body joints to balance regulation in terms of torque amplitude and variation. On the condition with the hands on the thighs, the contribution of the upper body remains significantly lower than the contribution of the lower body irrespective of beam widths. For spontaneous arm movements and for outstretched arms we find that the upper body (including the arms) contributes to the balancing to a similar extent as the lower body. Moreover, when the task becomes more difficult, i.e., for narrower beam widths, the contribution of the upper body increases, while the contribution of the lower body remains nearly constant. These findings lend further support to the hypothetical existence of an "upper body strategy" complementing the ankle and hip strategies especially during challenging dynamic balance tasks.
Buchstäblich auf der Flucht rutschte Kurt Goldstein sein Hauptwerk aus der Feder. Im Frühjahr 1934, während eines Zwischenaufenthalts in Amsterdam, schrieb er binnen weniger Monate "Der Aufbau des Organismus: Einführung in die Biologie unter besonderer Berücksichtigung der Erfahrungen am kranken Menschen". In diesem Buch entfaltete Goldstein seine auf der Basis von klinischen Erfahrungen gewonnenen physiologischen Anschauungen zu einer allgemeinen Theorie des Organismus. Zentraler Gedanke dieser Theorie war die These, dass sich die Leistungsvielfalt eines Organismus nicht als Summe möglichst exakt zu zergliedernder Einzelreaktionen beschreiben, sondern nur aus dem Gefüge ihres Zusammenwirkens erfassen lasse.
Two obligate cave-dwelling species of cyclopoid copepods (Copepoda, Cyclopoida) were discovered inside caves in central Thailand. Siamcyclops cavernicolus gen. et sp. nov. was recognised as as a member of a new genus. It resembles Bryocyclops jankowskajae Monchenko, 1972 from Uzbekistan (part of the former USSR). It differs from it by (1) lack of pointed triangular prominences on the intercoxal sclerite of the fourth swimming leg, (2) mandibular palp with three setae, (3) spine and setal formulae of swimming legs 3.3.3.2 and 5.5.5.5, respectively, and (4) specific shape of spermatophore. Metacyclops thailandicus sp. nov. resembles M. cushae Reid, 1991 from Louisiana (USA). It differs from it by (1) distal segment of the endopod of the fourth swimming leg with one apical spine, (2) the fifth swimming legs with one broad segment, (3) the spine formula of the distal segment of the exopod of the swimming legs 3.4.3.3, and (4) well developed anal operculum reaching articulation with caudal rami. Detailed descriptions of the habitats of the new species and up-to-date keys to the genera and subgenera of the Bryocyclops and Microcyclops groups are provided, along with an updated list of obligate groundwater species of Copepoda in Southeast Asia.
Kaum eine Zeit steht so sehr für die sexuelle Befreiung und Sprengung familialer Strukturen wie die 1968er (vgl. Herzog 2005). Kaum ein Märchen steht in der psychoanalytischen Deutung so sehr für den sexuellen Reifungsprozess und das Unabhängigwerden eines Kindes wie Der Froschkönig. Der vorliegende Artikel greift diese Verbindung auf, da gerade während der 68er-Bewegung verschiedene Wasser- und Amphibienfiguren in der Kinder- und Jugendliteratur (KJL) vorkommen, die stark an die Motive des Märchens erinnern. Besonders prominente Beispiele hierfür sind: Christine Nöstlingers Wir pfeifen auf den Gurkenkönig von 1972 sowie Mirjam Presslers Erzählung Goethe in der Kiste, die zwar erst 1987 erschienen ist, jedoch deutliche Züge des anti-autoritären Gedankenguts der Protestkultur aufweist. Diesen Texten ist gemein, dass ihre Motive augenscheinlich von einem Märchen geprägt sind, das von der Psychoanalyse als Sinnbild für den Reifungsvorgang eines Kindes bewertet wird, welches sich aus seiner inzestuösen Verstricktheit mit dem Vater lösen muss. Während Presslers Buch den Froschkönig explizit anzitiert, kann Nöstlingers Gurkenkönig als eine Schwell- und Schwellenfigur gelesen werden, die ähnliche Prozesse in Gang setzt wie die Märchengestalt. ...
While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.
Es werden vier Arten mit purpurn gefärbten Blattstielen beschrieben. Sie besiedeln besonders Gebiete mit schweren, lehmigen Böden. Draba kohlscheidensis und D. strigosula sind Arten mit eher kurzen Schötchen und hauptsächlich einfachen Haaren und Gabelhaaren, die in diesen Merkmalen D. praecox ähneln. D. aquisgranensis ist eine kräftige Art mit recht langen Schötchen und intermediär geteilten Haaren. Sie ähnelt typischem D. verna s. l. D. acutidentata vermittelt morphologisch zwischen D. glabrescens s. l. und D. verna s. l. und ist charakterisiert durch auffallend schmale Blätter mit unregelmäßig angeordneten, scharfen Zähnen.
Neuerdings werden in der ursprünglich nordamerikanischen Epilobium ciliatum-Gruppe drei Arten unterschieden. Intensive Studien im Aachener Raum haben gezeigt, dass weitere Sippen existieren. Im vorliegenden ersten Teil werden die Sippen, die morphologisch E. glandulosum entsprechen oder nahe stehen, besprochen. Neben E. glandulosum wird eine bisher nicht beachtete Sippe als E. pallidiglandulosum neu beschrieben. Sie unterscheidet sich von E. glandulosum unter anderem durch kleinere, zartrosa bis weißlich gefärbte Blüten, bleich- oder schwach blaugrün gefärbte Blätter und abweichend geformte Samen. Hybriden von E. glandulosum mit anderen Sippen der E. ciliatum-Gruppe werden vorgestellt.
Por ocasião do bicentenário da viagem dos naturalistas alemães Spix e Martius pelo Brasil (1817-1820), um grupo de pesquisadores ligados ao Instituto Martius Staden (São Paulo) refez em março de 2017 um trecho daquela expedição: de Ouro Preto a Diamantina. O principal objetivo foi estudar as continuidades e as mudanças ocorridas ao longo desses 200 anos. Estes foram os lugares visitados: 1) Ouro Preto, a antiga Vila Rica, capital da província de Minas Gerais; 2) no distrito de Mariana, as comunidades de Bento Rodrigues e Paracatu, destruídas pelo desastre ambiental ocorrido em 2015; 3) o Parque Nacional e o Santuário da Serra do Caraça, fundado em 1774; 4) as cidades de Sabará e do Serro, antiga Vila do Príncipe, e o Pico do Itambé (2052 metros), na Serra do Espinhaço, a divisa entre os biomas da Mata Atlântica e do Cerrado; e 5) a cidade de Diamantina, antigo Arraial de Tijuco, e seus arredores, incluindo um local de garimpagem.
Towards a visual middle voice : crisis, dispossession, and spectrality in Spain's hologram protest
(2018)
As a legitimizing mechanism for a doctrine of 'no alternatives,' crisis rhetoric tends to rely on distinctions between 'right' and 'wrong' that often turn political decisions into pseudo-choices between a legitimate and an illegitimate (even catastrophic) alternative. This binary logic also pervades the ways subjects are cast in this rhetoric as either active or passive, guilty or innocent, masters or victims. [...] The rhetorical reliance on the oppositions of passive/active or victims/perpetrators extends to several contexts of 'crisis' in Europe today, as Maria Boletsi shows. Against the backdrop of the crisis rhetoric and the monologic narratives and dualistic distinctions it produces, the need for alternative forms of expression is amplified. In this article, Boletsi makes a case for the "middle voice" as an expressive modality that can introduce alternative 'grammars' of subjectivity and agency to those on which dominant crisis rhetoric hinges. [...] To that end, Boletsi centers on a peculiar public protest in front of the Spanish Parliament in Madrid in April 2015, opposing a (then) newly introduced Spanish law—the "Law of Citizen Security" - which significantly restricted the citizens' freedom of assembly and expression in the name of security and crisis-management. Unlike any other protest, this one was not carried out by actual people, but by holographic projections of protesters. This 'hologram protest' put forward a form of dispossession, whereby bodies asserted presence in public space through their absence. Unsettling the boundaries between fiction and reality, materiality and immateriality, power and impotence, past and present, the protest fostered a spectral space that functioned as a visual analogue of the middle voice. The spectral subjectivity that this 'ghost march' enacted, both underscored and challenged politically induced conditions of dispossession and precarity, through and against these conditions. As a result, the protest recast crisis as a critical threshold from which alternative narratives of the present and the future can emerge.
Der Goldstandard zur Detektion eines erhöhten intrakraniellen Drucks ist das invasive Monitoring, z. B. mittels externer Ventrikeldrainage bei Intensivpatienten bzw. die Lumbalpunktion mit Messung des Liquoreröffnungsdrucks. Die am häufigsten angewendete klinische Untersuchung zum Ausschluss eines erhöhten ICP ist die Funduskopie. In den letzten 30 Jahren wurden zwei ultraschallbasierte Untersuchungsmethoden beschrieben um einen erhöhten ICP zu detektieren und die Funduskopie zu diesem Zweck zu ersetzen. Das Ziel unserer Studie war es, die Messung des Durchmessers der Sehnervenscheide (optic nerve sheat diameter, ONSD), der Undulation des Septum pellucidum (septum pellucidum undulation, SPU) hervorgerufen durch passive Rotation des Kopfes, und die Funduskopie mit einer invasiven Hirndruckmessung zu vergleichen. Der ONSD wurde mittels transbulbärer B-Mode Sonographie gemessen, für die Ermittlung der SPU wurde eine transtemporale M-Mode Sonographie durchgeführt. Zunächst schlossen wir gesunde Probanden ein, um die intrarater- und interrater- Reproduzierbarkeit der Ultraschalluntersuchungen zu berechnen. Die intrarater Reproduzierbarkeit des ONSD betrug 0,65 bis 0,84 und die interrater Reproduzierbarkeit war zwischen 0,69 und 0,91 (n=10). Die intrarater Reproduzierbarkeit der SPU war 0,29 und die interrater Reproduzierbarkeit ergab 0,26 (n=15). Anschließend untersuchten wir 45 Patienten, die für eine invasive Hirndruckmessung vorgesehen waren. Auch hier ermittelten wir die SPU und den ONSD, zusätzlich erfolgte die Funduskopie zum Ausschluss oder Bestätigung einer Stauungspapille. Die Sensitivität und Spezifität der drei Untersuchungen zur Ermittlung einer Erhöhung des intrakraniellen Drucks auf über 20 cm H2O wurden berechnet. Die Sensitivität der Funduskopie betrug 87,5% bei einer Spezifität von 25%. Im Vergleich hierzu betrug die Sensitivität der beiden Sonographieverfahren in Kombination 80% bei einer Spezifität von 100%. Die Ergebnisse der Studie zeigen, dass es zusätzlich zur Funduskopie sensitive und spezifische klinische Untersuchungsmethoden gibt zur Detektion eines erhöhten intrakraniellen Drucks im Alltag. Die Messung des ONSD und der SPU können nützliche Alternativen zur Funduskopie darstellen, optimalerweise in Kombination.
Are stereotypes possible pillars supporting the learning of a foreign language or are they possible sources of intercultural misunderstandings? In most coursebooks, intercultural materials are embedded in teaching units. The understanding of others is closely related to the understanding of someone's own culture as well as the target culture. Only when someone is aware of the own culture, then the target culture can be understood. In foreign language learning, it plays an important role, so that the knowledge of language structures alone is not enough to use the language successfully. At the same time, it requires cultural knowledge of the target language culture. This study focuses on the effects of culture-based fossilized prejudices on foreign language learning and to show the quantity of these stereotypes in given coursebooks. A coursebook analysis reveals to what extent stereotypes can be found in the respective GFL and TFL coursebooks. A compile of given stereotypes create an overall picture of foreign cultures. To what extent this overall picture reflects the reality has been handled at the end of this study
Este artigo se propõe a discutir algumas questões de interesse tradutológico referentes às três traduções brasileiras (1950; 1977; 2017) da obra Der Witz und seine Beziehung zum Unbewussten, de Sigmund Freud - cuja primeira publicação data de 1905. Parte-se de argumentos expostos em um debate entre o poeta e tradutor brasileiro Haroldo de Campos e o tradutor francês de Freud, Jean Laplanche, acerca das possibilidades de traduzir os chistes citados por Freud no referido livro, para identificar as diferentes estratégias adotadas pelos tradutores brasileiros. Longe de apresentar uma análise completa das diversas versões ou um cotejo exaustivo entre o original e as três (re)traduções, o que este trabalho visa é defender que elas constituem aproximações diferentes – porém todas válidas e potencialmente relevantes para o leitor-alvo - em relação a determinados aspectos da obra "original".
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
(2018)
Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
The illiberal turn in Europe has many facets. Of particular concern are Member States in which ruling majorities uproot the independence of the judiciary. For reasons well described in the Verfassungsblog, the current focus is on Poland. Since the Polish development is emblematic for a broader trend, more is at stake than the rule of law in that Member State alone (as if that were not enough). If the Polish emblematic development is not resisted, illiberal democracies might start co-defining the European constitutional order, in particular, its rule of law-value in Article 2 TEU. Accordingly, the conventional liberal self-understanding of Europe could easily erode, with tremendous implications.
Full reconstruction of large lobula plate tangential cells in Drosophila from a 3D EM dataset
(2018)
With the advent of neurogenetic methods, the neural basis of behavior is presently being analyzed in more and more detail. This is particularly true for visually driven behavior of Drosophila melanogaster where cell-specific driver lines exist that, depending on the combination with appropriate effector genes, allow for targeted recording, silencing and optogenetic stimulation of individual cell-types. Together with detailed connectomic data of large parts of the fly optic lobe, this has recently led to much progress in our understanding of the neural circuits underlying local motion detection. However, how such local information is combined by optic flow sensitive large-field neurons is still incompletely understood. Here, we aim to fill this gap by a dense reconstruction of lobula plate tangential cells of the fly lobula plate. These neurons collect input from many hundreds of local motion-sensing T4/T5 neurons and connect them to descending neurons or central brain areas. We confirm all basic features of HS and VS cells as published previously from light microscopy. In addition, we identified the dorsal and the ventral centrifugal horizontal, dCH and vCH cell, as well as three VSlike cells, including their distinct dendritic and axonal projection area.
Jede Gesellschaft oder Gemeinschaft wird von ihrer historischen Geschichte beeinflusst. Die gewachsenen Ansichten, Umgangsweisen und Strategien sind die Basis für die Weiterentwicklung jedes Gemeinwesens. Das Museum ist ein Ort der offenen und kritischen Auseinandersetzung mit dieser Geschichte und deren Wirkungen auf die Gegenwart. Es ist somit eine bildungspolitische Einrichtung, die aufgrund dieser gesellschaftlichen Aufgabe ihre besondere Bedeutung und Existenzberechtigung erhält. Museen sind in jeder Kultur und Gesellschaft ein wesentlicher Ort für die Fragen: Wo kommen wir her? Was verbindet uns? Besonderes in einer jungen Nation, die ihre Unabhängigkeit erst 1991 erlangt hat, ist eine Auseinandersetzung mit diesen Fragen dringend und wichtig.
Die Arbeit schlägt einen weiten Bogen vom Allgemeinen zum sehr Speziellen. Sie beginnt mit einer Darstellung der wichtigen Ansätzen und Studien zur Besucherforschung in Museen allgemein. Dabei wird nicht nur der Wandel in den Ansprüchen des Publikums aufgezeigt, sondern auch die Veränderungen der Konzeption und der Repräsentation der Museen selbst. Einen Schwerpunkt legt die Arbeit auf den Aspekt des Erzählens - das bedeutet, etwas sichtbar zu machen, was nicht offensichtlich ist: Kontexte, Reflexionen und Bezüge. Die Bedeutung der Kommunikation zwischen dem Museum und seinen Besuchern wurde in der Ethnologie bisher eher vernachlässigt.
The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with rage = 0.436/0.518 and with reGFR = −0.142/−0.207. For adjustment, these variables served as covariates in a linear regression model with cTnI as dependent variable. This adjustment model was then applied to a real-world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients.
Vielleicht denken derzeit die meisten zuerst an das Auto, wenn von 'Trabant' die Rede ist. Vielleicht sogar an dessen himmelblaue Ausführung, selbst wenn sie im Straßenbild inzwischen fremd geworden ist. Und wenn man 'fremd' mit 'unbekannt' übersetzt, dann trifft das den Trabanten nicht nur, weil der Begriff ein Fremdwort ist, sondern auch, weil unbekannt ist, aus welcher Fremde es stammt. Seine Herkunft ist nicht zweifelsfrei belegt. So hat man seinen Ursprung im Italienischen, im Deutschen oder im Türkisch-Persischen vermutet, von wo es über das Ungarische und Rumänische in die westeuropäischen Sprachen gelangt sein könnte. Im Grimm'schen Wörterbuch werden diese Annahmen jedoch samt und sonders als nicht stichhaltig verworfen. Umso wahrscheinlicher aber sei seine Herkunft aus dem Tschechischen, woher es zur Zeit der ersten Hussitenkriege entlehnt wurde, wobei dem dort schon im 15. Jahrhundert nachweisbaren 'dráb', dem 'fuszkrieger', im Deutschen die Endung '‑ant' hinzugefügt worden sei, ein Muster, wie es auch bei 'sarjant' oder 'brigant' verwendet worden war.
The ATP-binding cassette transporter TAPL translocates polypeptides from the cytosol into the lysosomal lumen. TAPL can be divided into two functional units: coreTAPL, active in ATP-dependent peptide translocation, and the N-terminal membrane spanning domain, TMD0, responsible for cellular localization and interaction with the lysosomal associated membrane proteins LAMP-1 and LAMP-2. Although the structure and function of ABC transporters were intensively analyzed in the past, the knowledge about accessory membrane embedded domains is limited. Therefore, we expressed the TMD0 of TAPL via a cell-free expression system and confirmed its correct folding by NMR and interaction studies. In cell as well as cell-free expressed TMD0 forms oligomers, which were assigned as dimers by PELDOR spectroscopy and static light scattering. By NMR spectroscopy of uniformly and selectively isotope labeled TMD0 we performed a complete backbone and partial side chain assignment. Accordingly, TMD0 has a four transmembrane helix topology with a short helical segment in a lysosomal loop. The topology of TMD0 was confirmed by paramagnetic relaxation enhancement with paramagnetic stearic acid as well as by nuclear Overhauser effects with c6-DHPC and cross-peaks with water.
The Wolof imperfective auxiliary di is compatible with event-in-progress, habitual and future readings. Furthermore, while varieties of all these readings are available for di when it sits in a syntactically low position, only future readings are available when it sits in a syntactically high position. We aim to account for this puzzle by combining several ingredients independently motivated in the literature: (i) event-relative circumstantial modality for event-in-progress, habitual, and a subset of future readings; (ii) metaphyisical modality for generalized future readings; (iii) the idea that syntactic height determines the type of modal anchor that projects a modal base. This study contributes to our understanding of the relation between syntactic height and modal flavor, as well as the nature of modal-aspectual interactions cross-linguistically.
Acute cholecystitis – a cohort study in a real-world clinical setting (REWO study, NCT02796443)
(2018)
Background: For decades, the optimal timing of surgery for acute cholecystitis has been controversial. Recent meta-analyses and population-based studies favor early surgery. One recent large randomized trial has demonstrated that a delayed approach increases morbidity and cost compared to early surgery within 24 hours of hospital admission. Since cases of severe cholecystitis were excluded from this trial, we argue that these results do not reflect real-world clinical situations. From our point of view, these results were in contrast to the clinical experience with our patients; so, we decided to analyze critically all our patients with the null hypothesis that the patients treated with a delayed cholecystectomy after an acute cholecystitis have a similar or even better outcome than those treated with an early operative approach.
Patients and methods: We retrospectively analyzed clinical data from all patients with cholecystectomies in the period between January 2006 and September 2015. A total of 1,723 patients were categorized into four groups: early (n=138): urgent surgery of patients with acute cholecystitis within the first 72 hours of the onset of symptoms; intermediate (n=297): surgery of patients with acute cholecystitis within an average of 10 days after the onset of symptoms; delayed (n=427): initial non-surgical treatment of acute cholecystitis with surgery performed within 6–12 weeks of the onset of symptoms; and elective (n=868): cholecystectomy within a symptom-free interval of choice in patients with symptomatic cholecystolithiasis without signs of acute cholecystitis.
Results: In a real-world scenario, early/intermediate cholecystectomy in acute cholecystitis was associated with a significant increase in morbidity and mortality (Clavien–Dindo score) compared to a delayed approach with surgery performed 6–12 weeks after the onset of symptoms. The adjusted linear rank statistics showed a decrease in the complication score with values of 2.29 in the early group, 0.48 in the intermediate group, –0.26 in the delayed group and –2.12 in the elective group. The results translate into a continuous decrease of the complication score from early over intermediate and delayed to the elective group.
Conclusion: These results demonstrate that delayed cholecystectomy can be performed safely. In cases with severe cholecystitis, early and/or intermediate approaches still have a relatively high risk of morbidity and mortality.
Die Autorin hat über vierzig Bücher über den Holocaust, die sich an junge Erwachsene richten, untersucht. Zusätzlich ist es ihr gelungen, durch die Einbeziehung aktueller Diskussionen über Neonazis, multikulturelle Erziehung, Rechte für Schwule und Lesben sowie über Toleranz den Bezug zur Gegenwart herzustellen. ...
Homollea Arènes (Rubiaceae, subfamily Ixoroideae, tribe Pavetteae) is a genus of shrubs and small trees endemic to western and northern Madagascar. The genus comprises five species occurring in dry deciduous forest, often in limestone areas. The five species are narrow endemics and their conservation status is either Endangered (4 species) or Critically Endangered (1 species). Homollea is characterized by few-flowered, pseudo-axillary, pedunculate inflorescences, well-developed calyces with the lobes much longer than the tube, laterally flattened seeds with a shallow, elongated to linear hilum and entire endosperm, ovules arising from the upper margin of the placenta, and, pollen grains with supratectal elements in the shape of microgemmae. Until now, three species were known and their descriptions are amended. Two further species, H. furtiva De Block sp. nov. and H. septentrionalis De Block sp. nov., are described as new for science. The five species are dealt with in detail: descriptions, distribution maps, conservation assessments, illustrations, lists of exsiccatae and an identification key are given.
Osthessen ist ein stark gegliederter Mittelgebirgsraum. Fruchtbare Tal- und Beckenlandschaften eignen sich für Ackerbau, die höheren Regionen vor allem zur Wald- und Weidewirtschaft. Es gibt zahlreiche salzhaltige Quellen. Kupferschiefer steht im nördlich gelegenen Richelsdorfer Gebirge an, und Eisenerze sind aus dem Vogelsberg und in lokalen Vorkommen zwischen Kalbach um Motten belegt. Während der Bronze- und Eisenzeit vollzieht Osthessen eine vielschichtige Entwicklung. Die Fulda-Werra-Gruppe, die in der Mittelbronzezeit einen einheitlichen Kulturraum bildet, zerfällt am Übergang zur Spätbronzezeit. Stattdessen befindet sich die Region nun im Kontakt- und Übergangsbereich verschiedener Kulturen. Auch in der Eisenzeit liegt Osthessen zunächst am nördlichen Rand der Hallstattkultur, bevor es in der Frühlatènezeit vorübergehend unmittelbarer Teil der Latènekultur wird. Nach den sog. Keltischen Wanderungen während der ausgehenden Mittel- und Spätlatènezeit rückt die Region dann wieder an die Peripherie der Latène- bzw. Oppidakultur. Während der gesamten Zeit ist Osthessen eine wichtige Kontakt- und Distributionszone, die stark durch Güter- und Ideenaustausch, aber auch durch Migration geprägt wird. Bei ersten Grabungen im Jahr 2016 wurde im Rahmen des LOEWE-Projekts der Stallberg näher untersucht, der von der älteren Forschung in die Eisenzeit datiert wurde, durch die Auffindung eines spätbronzezeitlichen Messers aber eine größere zeitliche Tiefe vermuten ließ. Bei den Ausgrabungen traten überraschenderweise Funde aus der Michelsberger Kultur zutage. Einige 14C-Daten konnten ein jungneolithisches Alter bestätigen, lieferten aber auch Daten aus dem Hochmittelalter.
Die Förderung von Fahrradmobilität und öffentlichem Verkehr ist ein wesentlicher Baustein zur Gestaltung einer ökologisch nachhaltigeren, sozial verträglicheren und ökonomisch tragfähigen Verkehrs- und Siedlungsentwicklung in Deutschland. Mit einer verbesserten intermodalen Verknüpfung werden beide Verkehrsträger attraktiver und somit häufiger genutzt. Öffentliche Verkehrsunternehmen gewinnen dadurch vergrößerte Einzugsbereiche von Haltestellen, können Spitzenbelastungen abfedern und verbessern ihr Image. Fahrradfahrenden ermöglicht die Kombination mit öffentlichen Verkehrsmitteln größere Reichweiten, was gerade auch in randstädtischen, suburbanen oder ländlichen Regionen bedeutsam werden kann. Letztlich leistet die Verknüpfung der beiden Verkehrsträger einen Beitrag zur Daseinsvorsorge und für den Klimaschutz.
Der Handlungsleitfaden wurde innerhalb des Forschungsprojektes „Verbesserte Integration des Fahrrads in den öffentlichen Verkehr – Systematische Erschließung von Handlungsoptionen und Bewertung von Best-Practices“ erarbeitet. Das Projekt wurde vom Bundesministerium für Verkehr und digitale Infrastruktur (BMVI) aus Mitteln zur Umsetzung des Nationalen Radverkehrsplans gefördert.
In seinem Buch Krisenproteste in Athen und Frankfurt. Raumproduktionen der Politik zwischen Hegemonie und Moment, das Ende des Jahres 2017 in der Reihe "Raumproduktionen" im Verlag Westfälisches Dampfboot erschienen ist, geht Daniel Mullis den Fragen nach, wie und unter welchen Bedingungen emanzipatorische Akteure Veränderungen erkämpfen können. Mullis ist es daran gelegen, Hegemonie und Moment als zwei sich ergänzende Modi der Politik zusammenzubringen und ein relationales und prozessuales Verständnis der gegenseitigen Bedingtheit von Raum und Politik zu entwickeln. Dazu verbindet er die politischen Philosophien von Ernesto Laclau und Chantal Mouffe (2000) einerseits und von Jacques Rancière (2002) andererseits mit der Raumtheorie Henri Lefebvres (1991). Illustriert wird dies mit den Krisenprotesten in Athen zwischen 2008 und 2014 und den Aktivitäten des Blockupy-Bündnisses in Frankfurt am Main zwischen 2012 und 2015. ...
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1) by the pro-inflammatory cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.
After publication of Blahnik and Holzenthal (2017), it was noticed that a large portion of the text had been accidentally removed from the "Phylogenetic and evolutionary comments" section during the proofing stage. The beginning of the deleted section completes the sentence on line 6 of page 129, which begins "The species included in the subgenus...". The Insecta Mundi editorial staff apologizes for this oversight. In order to provide context for the deleted excerpt, the entire "Phylogenetic and evolutionary comments" section is reproduced here, with the deleted text reincorporated. Insecta Mundi has also released a revised version of the Blahnik and Holzenthal (2017) manuscript, with this error corrected. However, the revised version is merely for convenience, and not an official peerreviewed article. Anyone wishing to reference the findings of Blahnik and Holzenthal (2017) should cite the original 2017 manuscript or this erratum. The references and figure plates cited in this section have also been reproduced here. ...
Aus einem ultranationalistischen Blickwinkel skizzierte Kuffner auf 32 Seiten und fünf beigefügten Karten die aus seiner Sicht notwendige territoriale Neuordnung Europas, die sowohl die allslawische Frage "od Šumavy až po Bajkal či Tichý Oceán" [vom Böhmerwald bis zum Baikalsee bzw. Pazifik] lösen als auch einen dauerhaften Frieden garantieren sollte. Die Hauptrolle dabei hatte er einem neu zu formierenden Staat zugedacht, dem er zwar den Namen "Čechy" (Böhmen) gab, der jedoch nicht nur die historischen Grenzen des Königreichs, sondern auch diejenigen der 1918 gegründeten ČSR deutlich überschritt. [...] Mit dieser überzogenen Denkschrift sollte Kuffer (unbeabsichtigt) einer antitschechischen Propaganda dies- und jenseits der 1919 sanktionierten Grenzen für 20 Jahre Dauermunition liefern: Binnen weniger Jahre avancierte sie zum meistzitierten tschechischen Werk im völkisch-deutschnationalen Schrifttum der 1920er und 1930er Jahre. Man glaubte in Kuffners Schrift "das heimliche Grundkonzept des tschechischen Imperialismus" aufgedeckt zu haben.
A full understanding of the origin, formation and degradation of volatile compounds that contribute to wine aroma is required before wine style can be effectively managed. Fractionation of grapes represents a convenient and robust method to simplify the grape matrix to enhance our understanding of the grape contribution to volatile compound production during yeast fermentation. In this study, acetone extracts of both Riesling and Cabernet Sauvignon grape berries were fractionated and model wines produced by spiking aliquots of these grape fractions into model grape juice must and fermented. Non-targeted SPME-GCMS analyses of the wines showed that several medium chain fatty acid ethyl esters were more abundant in wines made by fermenting model musts spiked with certain fractions. Further fractionation of the non-polar fractions and fermentation of model must after addition of these fractions led to the identification of a mixture of polyunsaturated triacylglycerides that, when added to fermenting model must, increase the concentration of medium chain fatty acid ethyl esters in wines. Dosage-response fermentation studies with commercially-available trilinolein revealed that the concentration of medium chain fatty acid ethyl esters can be increased by the addition of this triacylglyceride to model musts. This work suggests that grape triacylglycerides can enhance the production of fermentation-derived ethyl esters and show that this fractionation method is effective in segregating precursors or factors involved in altering the concentration of fermentation volatiles.
Nicht erst seit den scheinbar nicht enden wollenden Grimm-Publikationsjubiläen: 2012 Erstausgabe der Kinder- und Hausmärchen (KHM), 2016 Deutsche Sagen, 2019 Deutsche Grammatik erfährt die ›Gattung Grimm‹ eine erhöhte kulturelle und wissenschaftliche Aufmerksamkeit. Sie ist quasi ein ›Dauerbrenner‹, Jahr für Jahr, allerdings unter wechselnden Perspektiven. Die Fülle kann hier nur in einer fokussierten Auswahl vorgestellt werden. Ein gemeinsames Thema der drei vorliegenden Publikationen ist das Verhältnis der Gattung zu ganz unterschiedlichen Bildwelten. Erst die Verschränkung von Text und Bild hat, so eine Sicht, ein philologisches Editionsprojekt in einen kinderliterarischen Klassiker von Weltbedeutung transformiert. ...
There is a consensus among historians that the School of Salamanca brought something new to the development of early modern European legal thinking and methodology. Francisco de Vitoria is considered, not only by modern researchers but also by his contemporaries (from Melchor Cano onward), the origin of the school and its founding figure. He is famously claimed to have introduced Thomas Aquinas’s Summa theologiae as the fundamental text for theological lectures at the University of Salamanca and so prepared the ground for the upsurge of academic activity and intellectual brilliance of late or modern scholasticism at Spanish, Portuguese, and American universities. Regardless of the differences in the assessments of the late scholastics’ political stance (whether viewed as trailblazers on the way to human rights and a modern law of nations or as conservative imperialists, whose sole intent was the perpetuation and legitimation of the Spanish rule in the Americas), Vitoria and his followers are seen as intellectual innovators, opening the restrictive traditions of medieval scholarship to the modern exigencies of a globalized world. This almost universal image has recently been called into question, with Jacob Schmutz showing that Vitoria was not quite the first to introduce Aquinas’s Summa into the teaching of Salamanca’s theological faculty, and Thomas Duve recently asking outright: Did everything actually start with Francisco de Vitoria? ...
The conquista of the Americas confronted Spanish jurists educated in the legal concepts of the European medieval tradition with a different reality, pushing them to develop modern legal concepts on the basis of the European ius commune tradition. Traditionally, the School of Salamanca, theologians and jurists centred around the Dominican Francisco de Vitoria are credited with this intellectual renovation of moral and legal thought. However, the role earlier authors played in the process is still insufficiently researched. The Castilian crown jurist Juan López de Palacios Rubios is one of the most interesting authors of the early phase in the conquest of the Americas. His treatise about the Spanish dominion in the Americas is a central text that shows how at the beginning of the 16th century the knowledge and the experiences of the European past were applied to the American present and, in the process, were shaped into modern ideas.
Transmission of temporally correlated spike trains through synapses with short-term depression
(2018)
Short-term synaptic depression, caused by depletion of releasable neurotransmitter, modulates the strength of neuronal connections in a history-dependent manner. Quantifying the statistics of synaptic transmission requires stochastic models that link probabilistic neurotransmitter release with presynaptic spike-train statistics. Common approaches are to model the presynaptic spike train as either regular or a memory-less Poisson process: few analytical results are available that describe depressing synapses when the afferent spike train has more complex, temporally correlated statistics such as bursts. Here we present a series of analytical results—from vesicle release-site occupancy statistics, via neurotransmitter release, to the post-synaptic voltage mean and variance—for depressing synapses driven by correlated presynaptic spike trains. The class of presynaptic drive considered is that fully characterised by the inter-spike-interval distribution and encompasses a broad range of models used for neuronal circuit and network analyses, such as integrate-and-fire models with a complete post-spike reset and receiving sufficiently short-time correlated drive. We further demonstrate that the derived post-synaptic voltage mean and variance allow for a simple and accurate approximation of the firing rate of the post-synaptic neuron, using the exponential integrate-and-fire model as an example. These results extend the level of biological detail included in models of synaptic transmission and will allow for the incorporation of more complex and physiologically relevant firing patterns into future studies of neuronal networks.
We propose a spatiotemporal approach for modeling risk spillovers using time-varying proximity matrices based on observable financial networks and introduce a new bilateral specification. We study covariance stationarity and identification of the model, and analyze consistency and asymptotic normality of the quasi-maximum-likelihood estimator. We show how to isolate risk channels and we discuss how to compute target exposure able to reduce system variance. An empirical analysis on Euro-area cross-country holdings shows that Italy and Ireland are key players in spreading risk, France and Portugal are the major risk receivers, and we uncover Spain's non-trivial role as risk middleman.
Ich lernte Perry Rhodan 1961 kennen, als ich an einem Zeitungskiosk das erste Heft der Serie kaufte, das mittlerweile antiquarisch hoch gehandelt wird. Ich blieb der Serie ein paar Jahre treu, erwarb später auch die Schallplatte Count down (1969) des Sängers Norman Space (d. i. Uwe Reuss) sowie das Perry Rhodan Lexikon (1971) von H. G. Ewers und H. Scheer. In den Jahren, die uns Studenten kreativ politisierten, stellten wir Kauf und Lektüre der Serie ein und sprachen von Perry Rhodan nur noch als »Space Adolf«. Nicht als naiver Rezipient, sondern als Forschender, nahm ich später die Analyse eines Hefts der Serie in meine Habilitationsschrift Aspekte der literarischen Utopie (1976) auf. Soweit der persönliche Beitrag zur Rezeption. ...
We study tetraquark resonances with lattice QCD potentials computed for two static quarks and two dynamical quarks, the Born-Oppenheimer approximation and the emergent wave method of scattering theory. As a proof of concept we focus on systems with isospin I = 0, but consider different relative angular momenta l of the heavy b quarks. We compute the phase shifts and search for S and T matrix poles in the second Riemann sheet. We predict a new tetraquark resonance for l = 1, decaying into two B mesons, with quantum numbers I(JP) = 0(1−), mass MeV and decay width MeV.
The conception of the whole as a system, that is, as a totality determined by one principle or idea, has dominated the philosophical tradition from Kant and Hegel to Marxism - and, as Louis Althusser's critique of Hegelianism shows, not without implicit social, political, and ideological consequences. The possibility of breaking with the idealist tradition in all of these respects rests on the articulation of an alternative conception of the whole. Althusser advances the notion of the social whole as a complex unity that is constituted through its own effects - what he calls "overdetermination." Such overdetermination of the whole displaces the conception of the whole as totality (Hegel) in favor of Spinoza's notion of modal unity - the whole as singularity.
Four new species of the tribe Clytrini Kirby, 1837, Labidostomis bcharrensis sp. nov. (Lebanon), Tituboea friedmani sp. nov. (Israel), Tituboea harteni sp. nov. (United Arab Emirates) and Tituboea radeki sp. nov. (Yemen, Oman), and the formerly unknown females of Labidostomis damavandensis Rapilly, 1984 and Saudiclytra wittmeri Medvedev, 1979 are described. The following new synonyms are proposed: Coptocephala coptocephaloides (Lacordaire, 1848) = Coptocephala furthi Medvedev, 1992 syn. nov., Labidostomis rufa (Waltl, 1838) = Labidostomis rufa (Lacordaire, 1848) syn. nov., Tituboea olivieri (Lacordaire, 1848) = Tituboea femoralis Medvedev, 1962 syn. nov., Saudiclytra wittmeri (Medvedev, 1979) = Saudiclytra spinifemorata Medvedev, El Torkey & Al Dhafer, 2014 syn. nov. A neotype is designated for Clythra (Tituboea) olivieri Lacordaire, 1848. Tituboea decemguttata Walker, 1871 is considered as nomen dubium. The variability of the elytral pattern of Afrophthalma arabica (Bryant, 1957) is delimited. New country records and comments on distribution of Clytrini species from the eastern Mediterranean, the Near East and the Arabian Peninsula are presented.
Background/Aims: Sphingosine 1-phosphate (S1P) is considered as a key molecule regulating various cell functions including cell growth and death. It is produced by two sphingosine kinases (SK) denoted as SK-1 and SK-2. Whereas SK-1 has been extensively studied and has been appointed a role in promoting cell growth, the function of SK-2 is controversial, and both pro-proliferative and pro-apoptotic functions have been suggested. In this study we investigated whether renal mesangial cells isolated from transgenic mice overexpressing the human Sphk2 gene (hSK2-tg) showed an altered cell response towards growth-inducing and apoptotic stimuli.
Methods: hSK2-tg mice were generated by using a Quick KnockinR strategy. Renal mesangial cells were isolated by a differential sieving method and further cultivated in vitro. Lipids were quantified by mass spectrometry. Protein expression was determined by Western blot analysis, cell proliferation was determined by 3H-thymidine incorporation, and apoptosis was determined by a DNA fragmentation ELISA.
Results: We show here that kidneys and mesangial cells from hSK2-tg mice express the hSK2 as well as the endogenous mouse mSK2. hSK2 and mSK2 predominantly resided in the cytosol of quiescent transgenic cells. However, S1P accumulated strongly in the nucleus and only minimally in the cytosol of transgenic cells. Functionally, hSK2-tg cells proliferated less than control cells under normal growth conditions and were also more sensitive towards stress-induced apoptosis. On the molecular level, this was reflected by reduced ERK and Akt/PKB activation, and upon staurosporine treatment, by a sensitized mitochondrial pathway as manifested by reduced anti-apoptotic Bcl-XL expression and increased cleavage of caspase-9, downstream caspase-3 and PARP-1.
Conclusion: Altogether, these data demonstrate that SK-2 exerts an antiproliferative and apoptosis-sensitizing effect in renal mesangial cells which suggests that selective inhibitors of SK-2 may promote proliferation and reduce apoptosis and this may have impact on the outcome of proliferation-associated diseases such as mesangioproliferative glomerulonephritis.
Seit einigen Jahren ist bekannt, dass Sphingolipide nicht nur eine strukturgebende Funktion in der Plasmamembran aufweisen, sondern ebenfalls als Botenstoffe intra- und extrazellulär aktiv sind. Sphingosin-1-Phosphat (S1P) bildet dabei einen Schlüssel-Metaboliten, da es verschiedene Zellfunktionen wie Wachstum und Zelltod beeinflusst. Es wird durch zwei Isoformen der Sphingosinkinasen, SK1 und SK2, gebildet. Die SK1 wurde bereits gut untersucht und es konnte gezeigt werden, dass sie eine wichtige Rolle beim Zellwachstum einnimmt und einen entscheidender Regulator bei inflammatorischen Erkrankungen und Krebs darstellt. Über die SK2 ist soweit wenig bekannt und die Ergebnisse sind zum Teil kontrovers. Sowohl pro-proliferative als auch anti-proliferative Funktionen der SK2 wurden beschrieben. Andererseits handelt meine Arbeit von Nierenfibrose, da beschrieben wurde, dass Sphingolipide einen wichtigen Einfluss auf die Entwicklung chronischer Nierenerkrankungen nehmen. Nierenfibrose stellt das Endstadium chronischer Nierenerkrankungen dar und führt zu einer Akkumulation der Extrazellulärmatrix, Organvernarbung und zum Verlust der Nierenfunktion. Die SK1 spielt dabei eine protektive Rolle bei der Entstehung von Nierenfibrose. Deshalb sollte in dieser Arbeit die Rolle der Sk2 bei der Entstehung von Nierenfibrose untersucht werden.
Im ersten Teil meiner Arbeit wurde das Mausmodell der unilateralen Ureterobstruktion (UUO) verwendet, welches zur Entwicklung einer tubulointerstitiellen Nephritits und nachfolgender Fibrose führt. Es konnte dabei gezeigt werden, dass sowohl die Protein-Expression als auch die Aktivität der SK2 im fibrotischen Nierengewebe gesteigert wurden. Allgemein wiesen die SK2-/--Mäuse eine verminderte Fibrose in Folge des UUO auf im Vergleich zu den Wildtyp-Mäusen. Dies wurde bestätigt durch eine reduzierte Kollagenakkumulation, sowie eine verminderte Protein-Expression von Fibronektin-1, Kollagen-1, α-smooth muscle actin, connective tissue growth factor (CTGF) und Plasminogen-Aktivator-Inhibitor1 (PAI-1). Diese Effekte gingen einher mit einer gesteigerten Protein-Expression des inhibitorischen Smad7 und erhöhten Sphingosin-Spiegeln in SK2-/--UUO-Nieren. Auf mechanistischer Ebene vermindern die erhöhten Sphingosin-Spiegel die durch transforming growth factor-β (TGFβ) induzierte Kollagenakkumulation, die PAI-1- und CTGF-Expression, aber induzieren die Smad7-Expression in primären Nierenfibroblasten. In einem komplementären Versuch mit hSK2 tg-Mäusen wurde eine verstärkte Entstehung von Nierenfibrose mit erhöhter Kollagenakkumulation, sowie erhöhte Protein-Expressionen von Fibronektin-1, Kollagen-1, α-smooth muscle actin, CTGF und PAI-1 festgestellt. Die Smad7-Expression dagegen war vermindert.
Im zweiten Teil meiner Arbeit stand der glomeruläre Teil der Niere im Fokus und es wurde untersucht, ob die Überexpression der SK2 zu einer phänotypischen Veränderung der glomerulären Mesangiumzellen führt. Mesangiumzellen wurden dazu aus den hSK2 tg-Mäuse isoliert und charakterisiert. Es konnte gezeigt werden, dass hSK2 und mSK2 in den transgenen Zellen hauptsächlich in der zytosolischen Fraktion lokalisiert sind, während S1P ausschließlich im Kern akkumulierte. Weiterhin konnte eine verminderte Proliferation unter normalen Wachstumsbedingungen der hSK2 tg-Zellen im Vergleich zu den Kontrollzellen beobachtet werden. Die Zellen reagierten auch sensitiver auf Stress-induzierte Apoptose. Auf molekularer Ebene konnte dies durch eine reduzierte ERK- und Akt/PKB-Aktivierung erklärt werden. Nach Staurosporin-Behandlung wurde Apoptose durch den intrinsischen, mitochondrialen Apoptosesignalweg induziert. Dabei konnte eine reduzierte anti-apoptotische Bcl-xL-Expression und vermehrte Prozessierung von Caspase-9 und Caspase-3 und PARP beobachtet werden.
Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass eine verminderte tubulointerstitielle Fibrose-Entstehung durch die Deletion der SK2, sowie anti-proliferative und Apoptose-induzierende Effekte durch die SK2 in Mesangiumzellen nachgewiesen werden konnten. Somit könnten SK2-Inhibitoren die Entstehung tubulointerstitieller Fibrose und mit Proliferation assoziierte Erkrankungen wie mesangioproliferative Glomerulonephritis positiv beeinflussen.