Refine
Year of publication
Document Type
- Article (31128)
- Part of Periodical (11550)
- Book (8266)
- Doctoral Thesis (5713)
- Part of a Book (3967)
- Working Paper (3385)
- Review (2939)
- Contribution to a Periodical (2368)
- Preprint (2084)
- Report (1560)
Language
- German (42718)
- English (29217)
- French (1060)
- Portuguese (840)
- Spanish (309)
- Croatian (302)
- Multiple languages (258)
- Italian (198)
- mis (174)
- Turkish (168)
Has Fulltext
- yes (75568) (remove)
Keywords
- Deutsch (1076)
- Literatur (868)
- taxonomy (760)
- Deutschland (553)
- Rezension (511)
- new species (449)
- Rezeption (354)
- Frankfurt <Main> / Universität (341)
- Übersetzung (326)
- Geschichte (300)
Institute
- Medizin (7691)
- Präsidium (5170)
- Physik (4464)
- Extern (2738)
- Wirtschaftswissenschaften (2686)
- Gesellschaftswissenschaften (2369)
- Biowissenschaften (2184)
- Biochemie und Chemie (1975)
- Frankfurt Institute for Advanced Studies (FIAS) (1686)
- Center for Financial Studies (CFS) (1628)
Background/Aims: Alcohol (ethanol, EtOH) as significant contributor to traumatic injury is linked to suppressed inflammatory response, thereby influencing clinical outcomes. Alcohol-induced immune-suppression during acute inflammation (trauma) was linked to nuclear factor-kappaB (NF-ĸB). Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells. Methods: A549-cells were stimulated with interleukin (IL)-1β, or sera from trauma patients (TP) or healthy volunteers, with positive/negative blood alcohol concentrations (BAC), and subsequently exposed to EtOH (170 Mm, 1h). IL-6-release and neutrophil adhesion to A549 were analyzed. Specific siRNA-NIK mediated downregulation of non-canonical, and IKK-NBD-inhibition of canonical NF-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-subunits were detected using TransAm ELISA. Results: Both stimuli significantly induced IL-6-release (39.79±4.70 vs. 0.58±0.8 pg/ml) and neutrophil adhesion (132.30±8.80 vs. 100% control, p<0.05) to A549-cells. EtOH significantly decreased IL-6-release (22.90±5.40, p<0.05) and neutrophil adherence vs. controls (105.40±14.5%, p<0.05). IL-1β-induced significant activation of canonical/p50 and non-canonical/p52 pathways. EtOH significantly reduced p50 (34.90±23.70 vs. 197.70±36.43, p<0.05) not p52 activation. Inhibition of canonical pathway was further increased by EtOH (less p50-activation), while p52 remained unaltered. Inhibition of non-canonical pathway was unchanged by EtOH. Conclusion: Here, alcohol`s anti-inflammatory effects are mediated via decreasing nuclear levels of activated p50-subunit and canonical NF-ĸB signaling pathway.
We propose a long-run risk model with stochastic volatility, a time-varying mean reversion level of volatility, and jumps in the state variables. The special feature of our model is that the jump intensity is not affine in the conditional variance but driven by a separate process. We show that this separation of jump risk from volatility risk is needed to match the empirically weak link between the level and the slope of the implied volatility smile for S&P 500 options.
Why do banks issue contingent convertible debt? To answer this question we study comprehensive data covering all issues by publicly traded banks in Europe of contingent convertible bonds (CoCos) that count as additional tier 1 capital (AT1). We find that banks with lower asset volatility are more likely to issue AT1 CoCos than their riskier counterparts, but that CDS spreads do not react following issue announcements. Our estimates therefore suggest that agency costs play a crucial role in banks' ability to successfully issue CoCos. The agency costs may be higher for CoCos than for equity explaining why we observe riskier or lowly capitalized banks to issue equity rather than CoCos.
This thesis is concerned with quantum dynamical propagation methods suitable for high-dimensional systems, and their application to excitation energy transfer (EET), electron transfer (ET), and intra-molecular vibrational redistribution (IVR) in molecular aggregates. The theoretical description of these processes, which are often ultrafast – with time scales in the range of femtoseconds to picoseconds – is challenging, both with regard to quantum dynamical simulations and electronic structure calculations.
The present thesis comprises two parts. The first part concerns the implementation of a novel quantum dynamical method based on Gaussian Wavepackets (GWPs): the 2-Layer Gaussian-MCTDH (2L-GMCTDH) method. This method, which has recently been proposed in [S. Römer, M. Ruckenbauer, I. Burghardt, The Journal of Chemical Physics, 2013, 138, 064106] was implemented in a Fortran90 code and applied to various high-dimensional test systems. The second part of the thesis addresses the combined electronic structure and dynamical study of a novel type of donor-acceptor systems that have been investigated in a joint project with experimental collaboration partners at Strasbourg University. In both parts, numerical applications focus on high-dimensional model Hamiltonians for EET and ET processes.
Regarding the first part, the interest of using GWP-based methods is two-fold: First, GWPs represent spatially localized basis sets that are useful for on-the-fly dynamics in conjunction with electronic structure calculations. Second, they are naturally suited for the explicit representation of quantum mechanical system-bath type problems where a large number of vibrational bath modes are weakly perturbed from equilibrium. In this context, various methods exist that are based upon classically evolving GWP bases. A major improvement results from variational methods which involve optimized, non-classical GWP trajectories. In particular, the variational Gaussian-based Multi-Configuration Time-Dependent Hartree (GMCTDH) and its variational Multi-Configurational Gaussians (vMCG) variant were originally derived as semiclassical variants of the Multi-Configuration Time-Dependent Hartree (MCTDH) method. However, the G-MCTDH and vMCG methods mostly use Frozen Gaussian (FG) basis sets that are far less flexible than the single-particle (SPF) representation of standard MCTDH. As a consequence, a significantly larger number of GWPs are generally required to reach convergence. To remedy the lack of flexibility of the FG basis sets, the abovementioned two-layer (2L-G-MCTDH) approach has been introduced: Here, the first layer is composed of flexible SPFs, while the second layer is composed of low-dimensional FGs. The numerical scaling properties are significantly improved as compared with the conventional G-MCTDH and vMCG schemes. The first implementation of the method in an in-house Fortran90 code is presented, along with applications to (i) a model of site-to-site vibrational energy flow in the presence of intra-site vibrational energy redistribution (IVR) and (ii) a multidimensional donor-acceptor electron transfer system described within a linear vibronic coupling model. The second system relates to a model for ET at an oligothiophene-fullerene interface relevant to organic photovoltaics. Besides the description of the implementation, a detailed assessment of the convergence properties and comparison with multi-layer MCTDH (ML-MCTDH) benchmark calculations is presented. Finally, a perspective is given on the future combination with the existing ML-MCTDH scheme; indeed, such a combination is straightforward since the first layer of the 2L-G-MCTDH approach can be chosen to be orthogonal.
Regarding the second part of the thesis, two generations of a novel donor-acceptor (DA) system for organic photovoltaics applications, involving self-assembled block co-oligomers DA dyads and triads with perylene-diimide (PDI) accepter units, are addressed within a collaborative project with S. Haacke and S. Mery (University of Strasbourg). Based upon detailed excited-state electronic structure investigations along with quantum dynamical and kinetic studies, the relevant ET formation and recombination steps are characterized quantitatively, in view of optimizing the chemical design and reducing recombination losses.
In a first-generation variant of the abovementioned DA systems, which involves liquid-crystalline triads, we were able to show that a highly efficient inter-chain ET process prevails over intra-molecular ET, leading to fast recombination. Due to the latter, this system turns out to be inefficient for photovoltaic applications. To fully understand the elementary steps, high-dimensional quantum dynamics simulations were carried out using the ML-MCTDH method, in collaboration with Matthias Polkehn from our group. In the second-generation variant, which is in the focus of the present thesis, both the nanomorphology and the chemical design were modified. The present work, focuses upon the aspect of chemical design, by characterizing a series of modified DA’s, with donor units of varying length while the PDI accepter units remain unchanged. The intra-molecular ET is observed in these systems, but the processes are comparatively slow, of the order of tens to hundreds of picoseconds. Hence, a kinetic analysis using the Marcus-Levich-Jortner rate theory is employed. Among the main results of the study is that addition of an electron donating amine unit strongly increases the lifetime of the charge-separated state, and therefore reduced recombination losses.
Overall, the present thesis shows how a combination of high-dimensional quantum dynamics, electronic structure calculations, and vibronic coupling model Hamiltonians can be employed to obtain an accurate picture of EET, ET, and IVR in high-dimensional molecular assemblies. Furthermore, the 2L-GMCTDH method paves the way for accurate and efficient on-the-fly calculations; a suitable set-up for such calculations is currently in progress.
Erstmals trägt dieses nationale Assessment den Forschungsstand zum Klimawandel umfassend für alle Themenbereiche und gesellschaftlichen Sektoren zusammen. Womit müssen wir in Deutschland rechnen, welche Auswirkungen werden die Klimaveränderungen auf Wirtschaft und Gesellschaft haben, und wie können wir uns wappnen? 126 Autoren aus ganz Deutschland äußern sich zu Themen wie bereits beobachtete und zukünftige Veränderungen, Wetterkatastrophen und deren Folgen, den Projektionen für die Zukunft, den Risiken sowie möglichen Anpassungsstrategien.
Die Autoren stellen in verständlicher Sprache den aktuellen Forschungsstand dar und veranschaulichen die wichtigsten Gedanken in Grafiken und Tabellen. Alle Texte wurden mehrfach wissenschaftlich begutachtet. Klimawandel in Deutschland ist die erste Gesamtschau zu dem Themenkomplex, benennt offene Fragestellungen und liefert eine Grundlage für Entscheidungen im Zusammenhang mit dem Klimawandel.
Deutschland reiht sich damit ein in die Liste von Ländern wie die Vereinigten Staaten, Österreich und Großbritannien, in denen derartige Berichte bereits vorliegen.
Bestimmung des klinischen Nutzens systemischer adjuvanter Therapien beim frühen Mammakarzinom
(2017)
Die onkologische Therapie befindet sich im Umbruch. Hohe Erwartungen sind mit einer Reihe innovativer zielgerichteter Medikamente verknüpft, die sich derzeit in der klinischen Entwicklung befinden. Vor diesem Hintergrund erfahren Diskussionen um die Begriffe klinischer Nutzen oder klinische Relevanz neue Aktualität. Dies gilt auch für die Weiterentwicklungen der adjuvanten systemischen Therapie des frühen Mammakarzinoms. In Anbetracht der kurativen Zielsetzung erfolgt die Beurteilung des klinischen Nutzens einer adjuvanten Therapie maßgeblich anhand von Wirksamkeitsendpunkten. Der Fokus liegt hierbei auf Verbesserungen des krankheitsfreien Überlebens und des Rezidivrisikos. Eine Aussage zum Gesamtüberleben ist aufgrund der heute erreichten niedrigen Mortalitätsraten erst nach sehr langen Beobachtungszeiten möglich. Folgerichtig sollte neuen Medikamenten für die adjuvante Therapie ein klinischer Nutzen zugesprochen werden, wenn sie eine weitere Reduktion des Rezidivrisikos über den heutigen hohen Standard hinaus ermöglichen. Die Evidenz für etablierte adjuvante Therapiestandards beim frühen Mammakarzinom kann als objektiver Maßstab zum Vergleich herangezogen werden. Am Beispiel der adjuvanten endokrinen Therapie, der adjuvanten Polychemotherapie und der adjuvanten Anti-HER2-Therapie werden in diesem Übersichtsartikel die Anforderungen für den klinischen Nutzen neuer adjuvanter Therapien beim frühen Mammakarzinom abgeleitet.
Oncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as "clinical benefit" and "clinical relevance" are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.
With the Open Conference "Being a Citizen in Europe" in Zagreb (Croatia, 29-30 June 2015) external scholars were invited to connect to the bEUcitizen-project and to explore theoretical foundations and political as well as practical realities of today’s European citizenship. The structuring idea was to highlight potential core barriers towards EU citizenship and to do so by way of conceptual discussions as well as empirical analyses mapping a variety of citizenship practices in the EU. This was reflected in four thematic streams gathering contributions from both external and bEUcitizen researchers. The streams reflected on different kinds of barriers, conceptual and practical ones. They revolve around the normative promise of citizenship, the diversity of practices and possible paths of future development.
While stream 1 reflected on the dynamic of (re)configuring citizenship as a bounded or unbounded concept, stream 2 applied a comparative perspective on the diversity of rights-based citizenship practices. Stream 3 addressed the political dimension of EU-Citizenship and discussed a lack of citizenship participation as a farreaching barrier as well as possible remedies. Finally, stream 4 focused on linguistic diversity and the difficulties it creates regarding the conceptual and practical dimension of EU-citizenship. Taken together the contributions lucidly reflect the variety of disciplines cooperating in the bEUcitizen-project and their different points of view on EU-citizenship.
The crucial lesson from the contributions to the Open Conference for the theoretical task of WP 2 and the bEUcitizen-project more generally is that without conceptual clarity about the meaning of EU-citizenship the task of identifying practical barriers and evaluating the latter’s effects remains ambivalent. A shared understanding of the meaning of a (future) EU citizenship is still missing. What shall EU citizenship be or become: a fully-fledged democratic citizenship or a market-citizenship, bundling certain rights implied by the internal market freedoms? This undecided question is at the core of the debate on EU citizenship. In order to prevent citizens from turning their backs on the EU a public contestation of our understanding of the EU is needed. European democracy à venir requires an ongoing public debate about what European integration is all about and where it should lead us to – even and especially when there is no consensus about it.
An updated inventory of the Bromeliaceae for Costa Rica is presented including citations of representative specimens for each species. The family comprises 18 genera and 198 species in Costa Rica, 32 species being endemic to the country. Additional 36 species are endemic to Costa Rica and Panama. Only 4 of the 8 bromeliad subfamilies occur in Costa Rica, with a strong predominance of Tillandsioideae (7 genera/150 spp.; 75.7% of all bromeliad species in Costa Rica). 124 species (62.6%) grow exclusively epiphytic, additional 59 spp. (29.8%) are facultative epiphytes. The most diverse genus is Werauhia, with 59 species (29.8% of the Costa Rican bromeliad flora), followed by Tillandsia with 40 species (20.2%) and Guzmania with 28 spp. (8.6%).
We report new localities for the lizard Anolis salvini Boulenger, 1885, along the Pacific slopes of the Cordillera Central in Chiriquí province and the Comarca Ngöbe-Buglé of western Panama. These records extend the known geographic distribution of this species about 70 km eastwards. They also extend the known vertical distribution approximately 70 m uphill. Additionally, we provide the first record for the Caribbean slopes, an updated distribution map, photos of specimens from different localities, an analysis of a distress call, and comments on the morphology of this species.
Some anaerobic archaea and bacteria live on substrates that do not allow the synthesis of one mol of ATP per mol of substrate via substrate level phosphorylation (SLP). Energy conservation in these cases is only possible by a chemiosmotic mechanism that involves the generation of an electrochemical ion gradient across the cytoplasmic membrane that then drives ATP synthesis via an ATP synthase. The minimal amount of energy required for ATP synthesis is thus dependent on the magnitude of the electrochemical ion gradient, the phosphorylation potential in the cell and the ion/ATP ratio of the ATP synthase. It was always thought that the minimum biological energy quantum is defined as the amount of energy required to translocate one ion across the cytoplasmic membrane. We will discuss the thermodynamics of the reactions involved in chemiosmosis and describe the limitations for ion transport and ATP synthesis that led to the proposal that at least −20 kJ/mol are required for ATP synthesis. We will challenge this hypothesis by arguing that the enzyme energizing the membrane may translocate net less than one ion: By using a primary pump connected to an antiporter module a stoichiometry below one can be obtained, implying that the minimum biological energy quantum that sustains life is even lower than assumed to date.
Binary nucleation of sulphuric acid-water particles is expected to be an important process in the free troposphere at low temperatures. SAWNUC (Sulphuric Acid Water Nucleation) is a model of binary nucleation that is based on laboratory measurements of the binding energies of sulphuric acid and water in charged and neutral clusters. Predictions of SAWNUC are compared for the first time comprehensively with experimental binary nucleation data from the CLOUD chamber at European Organization for Nuclear Research. The experimental measurements span a temperature range of 208–292 K, sulphuric acid concentrations from 1·106 to 1·109 cm−3, and distinguish between ion-induced and neutral nucleation. Good agreement, within a factor of 5, is found between the experimental and modeled formation rates for ion-induced nucleation at 278 K and below and for neutral nucleation at 208 and 223 K. Differences at warm temperatures are attributed to ammonia contamination which was indicated by the presence of ammonia-sulphuric acid clusters, detected by an Atmospheric Pressure Interface Time of Flight (APi-TOF) mass spectrometer. APi-TOF measurements of the sulphuric acid ion cluster distributions (math formula with i = 0, 1, ..., 10) show qualitative agreement with the SAWNUC ion cluster distributions. Remaining differences between the measured and modeled distributions are most likely due to fragmentation in the APi-TOF. The CLOUD results are in good agreement with previously measured cluster binding energies and show the SAWNUC model to be a good representation of ion-induced and neutral binary nucleation of sulphuric acid-water clusters in the middle and upper troposphere.
In its weak field limit, Scalar-tensor-vector gravity theory introduces a Yukawa-correction to the gravitational potential. Such a correction depends on the two parameters, α which accounts for the modification of the gravitational constant, and μ∗−1 wwhich represents the scale length on which the scalar field propagates. These parameters were found to be universal when the modified gravitational potential was used to fit the galaxy rotation curves and the mass profiles of galaxy clusters, both without Dark Matter. We test the universality of these parameters using the temperature anisotropies due to the thermal Sunyaev–Zeldovich effect. In our model the intra-cluster gas is in hydrostatic equilibrium within the modified gravitational potential well and it is described by a polytropic equation of state. We predict the thermal Sunyaev–Zeldovich temperature anisotropies produced by Coma cluster, and we compare them with those obtained using the Planck 2013 Nominal maps. In our analysis, we find α and the scale length, respectively, to be consistent and to depart from their universal values. Our analysis points out that the assumption of the universality of the Yukawa-correction to the gravitational potential is ruled out at more than 3.5σ at galaxy clusters scale, while demonstrating that such a theory of gravity is capable to fit the cluster profile if the scale dependence of the gravitational potential is restored.
Entre as diversas perspectivas de pesquisa em educação, a Hermenêutica Objetiva se destaca hoje, na Alemanha, como uma das mais difundidas e reconhecidas abordagens da pesquisa sociológica qualitativa. O estágio de pós-doutorado realizado na Faculdade de Ciências da Educação - Instituto de Formação de Professores de Nível Secundário - da Universidade Johann Wolfgang Goethe em Frankfurt am Main foi uma das ações decorrentes do intercâmbio acadêmico firmado entre dois grupos de pesquisa, o "Teoria Crítica e Educação" (UFSCar - Brasil) e o "Reconstrução Pedagógica do Ensinar" (Universidade de Frankfurt - Alemanha). A partir dos conceitos que fundamentam o processo pedagógico (educação, instrução e formação), e da formulação de uma teoria pedagógica com base empírica, operada com o referencial teórico epistemológico da Hermenêutica Objetiva, o artigo aborda a situação atual da formação política nas escolas públicas alemãs. Como resultados, três aspectos gerais se destacam: 1) As análises sobre a metodologia da Hermenêutica Objetiva apontam a pertinência desse tipo de investigação na Educação, se o propósito for evidenciar os aspectos imanentes do processo pedagógico; 2) As reformas recentes na política educacional alemã indicam o processo de instrumentalização do ensino e o empobrecimento da formação em termos sociopolíticos; 3) A reconstrução empírica das aulas de política no ensino público alemão evidencia a superficialidade do conhecimento, o autoritarismo pedagógico, as práticas pedagógicas pseudo-democráticas; além da instrumentalização e judicialização da política, como temática de ensino.
The focus of this contribution is on the mode of capitalism within the industrialized sectors of "emerging markets". Particularly in the context of the rise of the BRIC (Brazil, Russia, India and China) this question has gained considerable importance, also for the development of the world economy as a whole. The core question is whether the type of capitalism within these economies is similar to the capitalist variety of the triad, or diverges in more or less permanent ways. The article gives a preliminary answer to this question, by developing a rough sketch of a "BRIC" model of capitalism and illustrating this model with the case of Brazil. In terms of theory, the article extends the Comparative Capitalism (CC) perspective to the BRICs. On the one side, the focus is on the classical questions of CC, i.e. the determinants of economic development and the differences to other types of capitalism, on the other side the relationship between these varieties and social inequality. It argues that the "state-permeated market economies" of the BRICs rely on clans as a mode of social coordination. As demonstrated by the case of Brazil, this type of capitalism can be quite successful, but is based on a highly unequal distribution of economic and political resources.
The contributions of Korean and Taiwanese authors to the many and varied formulations of interwar pan-Asianism have so far remained a relatively unexplored subject of scholarly research, despite an unbroken interest in the trajectory of state-based Japanese pan-Asianism. Focusing on Korean students and independence activists, this article discusses alternative configurations of regional unity and solidarity that emanated from the interactions among Korean, Taiwanese, and other Asian actors who resided in Tokyo during the 1910s and 1920s. When the ethnic-nationalist interpretations of the Wilsonian principle of self-determination failed to materialize, a portion of anti-colonial activists in Asia began to emphasize the need for solidarity by drawing on what they perceived as traditional and shared “Asian” values. While challenging the Western-dominated international order of nation-states that perpetuated imperialism, such notions of Asian solidarity at the same time served as an ideology of liberation from Japanese imperialism. Examining journals published by Korean students and activists, including The Asia Kunglun, this article adds another layer to the history of pan-Asianism from below, a perspective that has often been neglected within the larger context of scholarship on pan-Asianism and Japanese imperialism in Asia.
Orientation-selective DEER (Double Electron-Electron Resonance) measurements were conducted on a series of rigid and flexible molecules containing Cu(II) ions. A system with two rigidly held Cu(II) ions was afforded by the protein homo-dimer of copper amine oxidase from Arthrobacter globiformis. This system provided experimental DEER data between two Cu(II) ions with a well-defined distance and relative orientation to assess the accuracy of the methodology. Evaluation of orientation-selective DEER (os DEER) on systems with limited flexibility was probed using a series of porphyrin-based Cu(II)–nitroxide and Cu(II)–Cu(II) model systems of well-defined lengths synthesized for this project. Density functional theory was employed to generate molecular models of the conformers for each porphyrin-based Cu(II) dimer studied. Excellent agreement was found between DEER traces simulated using these computed conformers and the experimental data. The performance of different parameterised structural models in simulating the experimental DEER data was also investigated. The results of this analysis demonstrate the degree to which the DEER data define the relative orientation of the two Cu(II) ions and highlight the need to choose a parameterised model that captures the essential features of the flexibility (rotational freedom) of the system being studied.
Background: There is general consensus that the organizational and administrative aspects of academic study programs exert an important influence on teaching and learning. Despite this, no comprehensive framework currently exists to describe the conditions that affect the quality of teaching and learning in medical education. The aim of this paper is to systematically and comprehensively identify these factors to offer academic administrators and decision makers interested in improving teaching a theory-based and, to an extent, empirically founded framework on the basis of which improvements in teaching quality can be identified and implemented.
Method: Primarily, the issue was addressed by combining a theory-driven deductive approach with an experience based, “best evidence” one during the course of two workshops held by the GMA Committee on Personnel and Organizational Development in Academic Teaching (POiL) in Munich (2013) and Frankfurt (2014). Two models describing the conditions relevant to teaching and learning (Euler/Hahn and Rindermann) were critically appraised and synthesized into a new third model. Practical examples of teaching strategies that promote or hinder learning were compiled and added to the categories of this model and, to the extent possible, supported with empirical evidence.
Based on this, a checklist with recommendations for optimizing general academic conditions was formulated.
Results: The Frankfurt Model of conditions to ensure Quality in Teaching and Learning covers six categories: organizational structure/medical school culture, regulatory frameworks, curricular requirements, time constraints, material and personnel resources, and qualification of teaching staff. These categories have been supplemented by the interests, motives and abilities of the actual teachers and students in this particular setting. The categories of this model provide the structure for a checklist in which recommendations for optimizing teaching are given.
Conclusions: The checklist derived from the Frankfurt Model for ensuring quality in teaching and learning can be used for quality assurance and to improve the conditions under which teaching and learning take place in medical schools.
Following up on earlier investigations, the present paper analyzes construct validity of the impostor phenomenon. It examines the question whether the impostor phenomenon is a homogeneous construct or whether different types of persons with impostor self-concept can be distinguished on the basis of related characteristics. The study was conducted with professionals in leadership positions exhibiting a pronounced impostor self-concept (n = 183). Cluster-analytic procedures indicated the existence of two different types: one group which, in line with the literature (e.g., Clance, 1985), possessed traits classified as fairly unfavorable (“true impostors”) and another group which can be described as largely unencumbered (“strategic impostors”). The present study suggests two types of impostorism: “True” impostors characterized by the negative self-views associated with the construct definition, and more “strategic” impostors who seem to be less encumbered by self-doubt. It is assumed that “strategic impostors” are characterized by a form of deliberate self-presentation. Therefore, the impostor self-concept cannot principally be viewed as a dysfunctional personality style. This distinction should be more carefully considered in further research and in therapeutic interventions.
Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77–22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80–32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21–5.85) and full siblings (OR=4.59, 95% CI: 4.39–4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.
Erich Oberdorfer (1905-2002)
(2003)
Am 23. September 2002 verstarb nach einem erfüllten Leben Prof. Dr. Dr. h.c. Erich Oberdorfer im Alter von 97 Jahren. Es war ihm vergönnt, im Kreise seiner Familie ruhig einzuschlafen in seinem Haus in Freiburg-St. Georgen. Er konnte noch bis kurz vor seinem Tode geistig rege die Geschicke der Pflanzensoziologie und der Taxonomie der Pflanzen verfolgen. Mit ihm verließ uns einer der letzten Universal-Pflanzensoziologen, der meisterhaft pflanzensoziologisch-pflanzengeographische und floristisch-taxonomische Erkenntnisse zu verbinden wusste.
Bücherschau
(2002)
Der Harz ist eine alte, eigenartige Kulturlandschaft mit einer sehr vielseitigen Naturausstattung und einer wechselvollen Kulturgeschichte über gut 1000 Jahre. In mehreren Kapiteln werden zunächst die natürlichen Grundlagen (Erdgeschichte, Relief, Gesteine, Böden, Klima, Flora, Landschaftsgliederung) dargestellt. Die Kulturgeschichte insbesondere des Oberharzes ist von Entwicklungen, Rückschlägen und Niedergang des Bergbaus geprägt. Sie hat sich stark auf die Vegetation und das Landschaftsbild ausgewirkt. Eigentliche Haupterwerbs-Landwirtschaft war dagegen dort nie von Bedeutung. Selbst heute, wo Bergbau und Industrie erloschen oder rückläufig sind, gibt es viele Relikte und Nachwirkungen in der Landschaft, die auch die aktuelle Vegetation mit bestimmen. Im Harz bemüht man sich, einen sinnvollen Kompromiß zwischen Naturschutz und Tourismus zu finden. Abschließend wird versucht, eine erste Übersicht der Pflanzengesellschaften des Harzes zu geben.
In einer Ganztagesexkursion wird das floristisch wie faunistisch für Norddeutschland herausragende Bodetal am Nordrand des Harzes besucht. Das Naturschutzgebiet besitzt eine eindrucksvolle Geomorphologie mit einem tief eingeschnittenen Kerbtal und beherbergt eine Vielzahl von Vegetationstypen mit unterschiedlichen Wärme- und Feuchteansprüchen. Kennzeichnend ist das Mosaik an sauren Gesteinen, auf denen Schlucht- und Blockhaldewälder, bachbegleitende Staudengesellschaften und bodensaure Felsrasen und Gebüsche angetroffen werden.
Die Brockenexkursion umfasst die Bergfichtenwälder, Moore und Bergheiden von 850 m ü. NN bis zur Brockenkuppe 1142 m ü. NN. Das Gebiet ist, ausgehend von den Fichtenwäldern und Mooren, relativ artenarm, aber strukturreich. Der Weg zum Brocken führt zunächst zwar durch ausgedehnte Fichtenforsten, dann auch durch die Bergfichtenwälder (Calam agrostio villosae-Piceetum, Sphagno girgensohnii-Piceetum, Betulo carpaticae Piceetum) auf dem Königsberg und am Brocken. Ausgedehnte Moore finden wir zwischen Torfhaus und dem Brocken sowie an den Brockenhängen, mit folgenden Gesellschaften: Eriophoro-Trichophoretum cespitosi, Sphagnetum magellanici, Eriophorum angustifolium-Sphagnum-Gesellschaft, Caricetum nigrae u.a. Von besonderem Interesse, wenn auch nur kleinflächig vorhanden, sind die subalpinen Bergheiden mit der Anemone micrantha-Calluna vulgaris-Gesellschaft auf der Brockenkuppe, die trotz der hohen Besucherzahlen nicht gefährdet ist. Die Kenntnis der Pflanzenarten der Alpen sowie der bedeutendsten Gebirge der übrigen Kontinente kann im 112 Jahre alten Brockengarten vervollständigt werden.
Die Exkursion vermittelt Eindrücke von montanen Grasland-Gesellschaften des Ober- und Unterharzes als Resten einer historischen Kulturlandschaft mit vorwiegend extensiven bis halbintensiven Nutzungseinflüssen. Im Bereich Rotes Bruch - Großer Rappenberg bei Benneckenstein wachsen relativ artenarme Kleinseggensümpfe (Caricion fuscae) und verschiedene Ausprägungen von Sumpfdotterblumen-Wiesen (Calthion palustris). Auf dem Großen Rappenberg gibt es Borstgrasrasen (Violion caninae) und unterschiedlich intensiv bewirtschaftete Goldhafer-Bergwiesen (Polygono-Trisetion). Auf der Jordanshöhe bei St. Andreasberg wachsen verschiedene Ausprägungen der Goldhafer-Bergwiesen mit Übergängen zu Borstgrasrasen. In einem Versuch werden seit 1988 verschiedene Mahdvarianten zur Regeneration und Erhaltung von Bergwiesen auf Dauerflächen verfolgt.
DieNaturschutzgebiete Hainholz und Staufenberg am südwestlichen Harzrand wurden mit den Methoden der Naturwaldforschung untersucht. Beim Hainholz handelt es sich um eines der letzten naturnahen Buchenwaldgebiete in der Gipskarstlandschaft des Zechsteins. Vorherrschend sind trockenheitsertragende bis mäßig frische Kalkbuchenwälder (Carici-Fagetum, Hordelymo-Fagetum ). Der kegelförmige Staufenberg wird durch basenarme Grauwacken- und basenreiche Diabasstandorte geprägt, auf denen von der submontanen bis zur montanen Stufe oligo- bis mesotrophe Buchenwälder (Luzulo-Fagetum, Galio odorati-Fagetum) in allen Expositionen auftreten. Während der Staufenberg seit Ausweisung als Naturwald sich mehr als drei Jahrzehnte weitgehend ungestört entwickeln konnte, wurden im Hainholz 1997 durch einen Sommergewittersturm Buchenbestände z.T. großflächig geworfen. Die Ergebnisse der floristischen und vegetationskundlichen Untersuchungen konzentrieren sich auf drei Aussagen im Zusammenhang mit dem Mosaik-Zyklus-Konzept zur Dynamik von Buchenwäldern: 1. Mit der Einstellung der forstlichen Nutzung gehen die Artenzahlen in Buchenwäldern der Optimalphase zurück. Erst bei großflächigen Störungen wie z.B. Windwurf mit freigelegtem Mineralboden steigen die Artenzahlen wieder an. 2. Fehlende Nutzung begünstigt in der Optimalphase die Buche. Ohne großflächige Störung erfolgt auch die Verjüngung überwiegend durch die schattentolerante Buche. Erst bei großflächiger Störung treten typische Pioniersträucher auf, aber auch dann dominieren auf den basenreichen Böden des Hainholzes die schattentoleranten Baumarten, die bereits vor dem Windwurf in der Verjüngungsschicht des geschlossenen Altbestandes reichlich vorhanden waren. Ein Baumartenwechsel findet nicht statt. 3. Nichtwaldarten verschwinden nach Einstellung der forstlichen Nutzung in Buchenwäldern der Optimalphase. Sie treten nach großflächigen Windwürfen erneut auf, allerdings standörtlich stark unterschiedlich in Raum und Zeit. Insgesamt lassen die Ergebnisse aus dem Hainholz den Schluss zu, dass ohne forstliche Eingriffe auch bei katastrophalen, großflächigen Störungen die Regenerationsprozesse in mitteleuropäischen Buchenwäldern rascher verlaufen als bisher vielfach angenommen wird. Da dies gleichzeitig mit einem Anstieg der Artendiversität verbunden ist, der ohne großflächige Störung ausbleibt, sollte man solchen Katastrophen aus der Sicht des Naturschutzes eher positiv und gelassen gegenüberstehen.
This thesis reports on the results obtained by expression photoactivatable adenylyl cyclase from Beggiatoa spp. (bPAC) in cholinergic neurons from Caenorhabditis elegans (C. elegans) and the characterization of the role of a single neuron, RIS, during locomotion in the adult animal.
Pharmacological activation of adenylyl cyclases through Forskolin is known to induce increased neuronal output in diverse model organisms through a protein kinase A (PKA) dependent mechanism. Nevertheless, pharmacological assays are not spatially restricted, do not allow for precise and acute activation nor to cessation of the signal. Thus, an optogenetic approach for was selected trough the expression of photoactivatable adenylyl cyclase from Beggiatoa spp. (bPAC) in cholinergic neurons of Caenorhabditis elegans (C. elegans). This model organism was chosen due to its transparency, ease of maintenance, fast generation cycles as well as for being an eutelic animal. Further, its genome has been fully sequenced and the connectome of the neuronal network is known, thus allowing for precise analysis of neuronal function. Furthermore, the molecular mechanisms governing neuronal functions are well conserved up to primates. Mainly two optogenetical tools were applied, bPAC and the light gated cation channel channelrhodopsin 2 (ChR2).
Behavioral assays of bPAC photostimulation in cholinergic neurons recapitulated previous work performed with the photoactivatable adenylyl cyclase from Euglena gracilis (EuPACa), in which swimming frequency and speed on solid substrate were increased. Electrophysiological recordings of body wall muscle (BWM) cells by Dr. Jana F. Liewald showed that bPAC photoactivation led to an increase in miniature postsynaptic current (mPSC) rate and, in contrast to ChR2 invoked depolarization, also amplitude. Analysis of mutants deficient in neuropeptidergic signaling (UNC- 31) via electrophysiology performed by Dr. Jana F. Liewald showed that the increase in mPSC amplitude due to bPAC photoactivation requires neuropeptide release. This was confirmed by co-expression of bPAC with the neuropeptide marker NLP-21::Venus and subsequent fluorescence analysis of release, exploiting the fact that released neuropeptides are ultimately degraded by scavenger cells (coelomocytes). These were enriched with NLP-21::Venus after bPAC photostimulation, but no fluorescence could be observed in the UNC-31 mutants.
Additional analysis of the electrophysiological data performed by myself showed no modulation of mPSC kinetics dues to neuropeptidergic release induced by bPAC. Hence, neuropeptide release and action sites were in the cholinergic neurons, the latter including cholinergic motoneurons.
Dr. Szi-chieh Yu provided electron microscopy images of high pressure frozen, bPAC or ChR2 expressing animals. These were tagged by myself for automatic analysis of ultrastructural properties of the cholinergic presynapse, also during photoactivation of both optogenetic tools. Photoactivation of both induced a reduction of synaptic vesicles, with ChR2 showing a more severe effect. In contrast to ChR2, though, bPAC also reduced the amount of dense core vesicles (DCV), the neuropeptide transporters. Additionally, long bPAC photoactivation as well as ChR2 photoactivation led to the appearance of large vesicles (LV), presumably in response to the increased SV fusion rate. bPAC photostimulation also induced an increase in SV size, not observed after ChR2 photostimulation. In UNC-31 mutants, bPAC photostimulation could not lead to the SV size increase, a further argument for the presynaptic effect of the released neuropeptide. Additional analysis of electrophysiology paired with pharmacology, performed by Dr. Jana F. Liewald, showed that mPSC amplitude increase requires the function of the vesicular acetylcholine transporter.
A further effect observed in the ultrastructure of bPAC photostimulated cholinergic presynapses was a shift in the distribution of SV regarding the dense projection. An analysis of cAMP pathway mutants showed that synapsin is required for bPAC induced behavior effects. Synapsin is known to mediate SV tethering to the cytoskeleton. Here, I show evidence for a new role of synapsin in controlling the availability of DCVs for fusion and thus, in neuropeptidergic signaling.
In the second part of my thesis I characterized the function of the GABAergic interneuron RIS in the neuronal network of C. elegans. RIS was shown to induce lethargus, a sleep-like state, during all larval molts, but its function in the adult animal was not yet described. Specific RIS expression of ChR2 achieved by a recombinase based system allowed to acutely depolarize the neuron during locomotion, which led to an acute behavioral stop. Diverse signal transduction pathway mutants were analyzed showing that the phenotype was induced by neuropeptidergic signaling. Through mutagenesis followed by whole genome sequencing data analysis as well as analysis of RIS specific RNA sequencing data further narrowed the signal transduction pathway to mediate the locomotion stop behavior. Since the neuropeptide and, to some extent, the neuron are conserved across nematodes, an argument is outlined in favor of the conservation of this sleep-like state.
In addition, since ChR2 could induce neuropeptidergic signaling from RIS, secretion of vesicles is regulated by variable pathways depending on the neuronal identity. Nevertheless, expression of bPAC in RIS allowed to optogenetically increase the probability of short stops, as observed by expression of a calcium sensor (GCaMP) in RIS and analysis of its intrinsic activity in the adult animal.
In the title compound, C17H18N2O, the central carbon atom with the OH substituent and one of the (E)-benzylideneamino substituents are disordered over two sets of sites with occupancies of 0.851 (4) and 0.149 (4). The relative positions of the two disorder components is equivalent to a rotation of approximately 60° about the C—N single bond. In the crystal, the molecules are held together by O—H...N hydrogen bonds, forming simple C(5) chains along the b-axis direction. In addition, pairs of the chains are further aggregated by weak C—H...π interactions.
Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures—namely the ER surface and the membranous webs—based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.
Der 1994 in Niedersachsen gegründete Nationalpark Harz wird mit seinen Aufgaben, Zielen und Naturschutzmaßnahmen vorgestellt. Die Flora des Nationalparks weist zahlreiche Besonderheiten auf, darunter zwei Gefäßpflanzenarten und drei Flechtenarten, die innerhalb von Niedersachsen ausschließlich hier Vorkommen. Exkursionsziele im Rahmen der Tagung sind hochmontane Borstgrasrasen (Violion caninae) und Bergheiden (Vaccinio-Callunetum) mit Flachbärlapp-Vorkommen am Großen Sonnenberg, das Sonnenberger Moor als typisches Harzmoor, über große Flächen als Rasenbinsen-Hochmoor ausgeprägt, Schluchtwälder im Eckertal (Fraxino-Aceretum) mit Vorkommen von Lunaria rediviva, artenreiche Kleinseggensümpfe (u.a. mit zahlreichen Carex-Arten und Pinguicula vulgaris) entlang von Forstwegen sowie das Luchsgehege an den Rabenklippen.
Der vorliegende Beitrag beschäftigt sich mit der Flora und Vegetation des Hohen Meißners und seines östlichen Vorlandes (Werra-Meißner-Kreis, Nordhessen). Auf dem Meißner selbst sind, neben naturnahen Bereichen mit Basaltblockhalden und Schutthangwäldern (Fraxino-Aceretum) vor allem gut ausgebildete Beispiele montaner Grünlandkomplexe erhalten geblieben. Sie gehören pflanzensoziologisch zu den Bergwiesen (Polygono-Trisetion), Feuchtwiesen (Calthion), Borstgrasrasen (Violion caninae) und Braunseggenrieden (Caricion fuscae). Im östlichen Meißnervorland sind größere Karstgebiete zu finden, die weithin von Kalkmagerrasen (Mesobromion) eingenommen werden. Daneben treten in den Magerrasenkomplexen Glatthaferwiesen (Arrhenatherion) und kleinflächig Pionierrasen (Alysso-Sedion) auf. Die Ackerflächen sind noch heute reich an gefährdeten Ackerwildkrautgesellschaften, insbesondere die an die Magerrasen angrenzenden, klein parzellierten Kalkäcker mit vielen Arten des Caucalidion. Sowohl die Ackerwildkrautvegetation als auch die Magergrünlandkomplexe sind Gegenstand von naturschutzfachlichen Pflege- und Entwicklungsmaßnahmen, die ebenfalls erläutert werden.
Am Beispiel zweier im hessisch-thüringischen Grenzgebiet gelegener Muschelkalk-Felshänge des mittleren Werratales wird dargestellt, welche Vegetationsveränderungen vom Mittelalter bis in die Gegenwart an natürlichen Waldgrenzstandorten sowie in ihrer näheren Umgebung stattgefunden haben und welche Konsequenzen für den Naturschutz sich daraus ergeben. Markante Wendepunkte der Landnutzung sind die mit der deutlich zunehmenden Besiedelung seit dem 6. Jahrhundert vorgenommenen Rodungen, die Aufgabe des Weinbaues seit Anfang des 17. Jahrhunderts sowie der Rückgang der Schafhaltung nach 1850 und nach 1990. Die wichtigsten Vegetationstypen der Felshänge (Wald-, Saum- und Rasengesellschaften) werden vorgestellt. Qualitative und quantitative Veränderungen offener Trockenstandorte infolge sekundärer Sukzessionsprozesse kennzeichnen die gegenwärtige Situation. Rasengesellschaften sind aufgrund geringer oder fehlender Nutzungsintensität vielfach von Flächenverlusten durch Gehölzausbreitung betroffen. Dies gilt in besonderem Maße für ehemals beweidete Bestände. Mit der (Rück-)Einwanderung der Rotbuche in die Baumschicht von Laub- und Nadelwäldern trockener Kalkstandorte sind qualitative Veränderungen der Strauch- und Krautschicht verbunden. Sie äußern sich insbesondere in einem Rückgang lichtliebender, zum Teil thermophiler Arten. Die aktuelle Gefährdung der betrachteten Vegetationstypen hängt stark von deren Natürlichkeitsgrad ab. Naturschutz-Pflegemaßnahmen (v. a. Beweidung) sollten in erster Linie auf halbnatürlichen anthropo-zoogenen Kalk-Halbtrockenrasen durchgeführt werden, da hier die tiefgreifendsten Veränderungen durch Sukzession zu erwarten sind. Naturnahe Blaugras-Rasen und Saumgesellschaften können weitgehend sich selbst überlassen bleiben, da eine Sukzession hier nur langsam verläuft und zu erwarten ist, dass ihre Arten im Bereich natürlicher Waldgrenzen immer geeignete Bedingungen finden werden, wenn auch auf kleinerer Fläche.
Exkursionen
(2002)
Die Exkursionen A-H werden Einblicke in Flora, Vegetation, Ökologie, Landschaften und Naturschutzfragen Südniedersachsens und anliegender Teile von Sachsen-Anhalt, Hessen und Thüringen geben. Die übrigen Exkursionsziele verteilen sich über den Harz, von seinen Randgebieten bis zum Brocken als höchstem Berg Norddeutschlands.
Kurzfassungen der Vorträge: Geobotanik in Göttingen von Albrecht von Haller bis Heinz Ellenberg
(2002)
In den gut 250 Jahren Geschichte der Universität Göttingen sind alle Zweige der Geobotanik hier gepflegt worden. Es begann mit den Florenwerken von Göttingen und der Schweiz, die ALBRECHT VON HALLER (1708-1777, in Göttingen 1736-53) verfasste. Eine Serie von weiteren Floren von Göttingen und Umgebung fand ihren Höhepunkt in der Flora von Südhannover von ALBERT PETER (1901).
Die Floristisch-soziologische Arbeitsgemeinschaft ist eine der größten geobotanischen Gesellschaften im deutschsprachigen Raum mit etwa 1300 Mitgliedern aus Wissenschaft, Praxis und anderen Interessierten an Fragen von Flora, Vegetation, Ökologie und Naturschutz. Sie hat seit 1927 ein weites Stück des Weges der Geobotanik begleitet, insbesondere die Pflanzensoziologie, die sich seit den 1920er Jahren zunächst in Europa, später weltweit entwickelte. Wichtiges Bindeglied war lange Zeit REINHOLD TÜXEN, der Begründer und über viele Jahrzehnte der Vorsitzende unserer Arbeitsgemeinschaft, gleichzeitig einer der prominentesten Vertreter der Vegetationskunde überhaupt (s. auch DIERSCHKE 1980). Unsere Zeitschrift trägt seit 1981 seinen Namen.
Vorwort
(2002)
75 Jahre einer Vereinigung sind eine lange Zeit und können Anlass zu Festlichkeiten, Rückbesinnung und Vorausschau sein. Zum 50. Geburtstag unserer Arbeitsgemeinschaft gab es eine umfangreiche Festschrift mit Beiträgen zahlreicher Mitglieder. Dieses Mal ist es ein erweiterter, bunt ausgeschmückter Tagungsband. Hierdurch werden auch diejenigen Mitglieder beteiligt, die nicht unmittelbar dabei sein können. Ausführliche Darstellungen der Exkursionsziele, teilweise verbunden mit allgemeineren Fragen, mögen auch breiteres Interesse erwecken und vielleicht zu privaten Reisen in unsere interessanten norddeutschen Landschaften anregen.
Die mitochondriale Innenmembran (IM) besteht aus zwei Subkompartimenten. Der
Cristae Membran (CM) und der inneren Grenzmembran (IBM), welche durch die runden und
schlitzartige Strukturen der Christa Junctions (CJs) verbunden werden Der MICOS-Komplex
ist an den CJs lokalisiert und besteht aus mindestens 6 Komponenten, Mic60, Mic27, Mic26,
Mic19, Mic12 und Mic10. Es ist bekannt, dass der MICOS-Komplex essentiell für die Stabilität der CJs ist. Die in dieser Arbeit gezeigten Ergebnisse, geben Aufschluss darüber, wie sich
einzelne MICOS-Komponenten auf die Stabilität von Cristae und CJs im Modellsystem Hefe (S
cerevisiae) auswirken. Zu Beginn dieser Arbeit war zum einen bekannt, dass die MICOSKomponente
Mic60 essentiell für die Bildung von CJs ist. Zum Anderen wurden im Vorfeld
dieser Arbeit Interaktionen von Mic60 mit Proteinen in der mitochondrialen Außenmembran,
vor allem Proteinkomplexe mit ȕ-barrel-Proteinen identifiziert. Diese Interaktionen werden
über den evolutionär, konservierten C-Terminus von Mic60 vermittelt.
ȕ-barrel Proteine besitzen eine charakteristische Peptidsequenz, die ȕ-Sequenz. Diese
dient nach dem Import der ȕ-barrel Proteine in die Mitochondrien als Signalpeptid für den
SAM-/TOB-Komplex, welcher daraufhin die Proteine in die Außenmembran insertiert. In
dieser Arbeit wurde ebenfalls eine ȕ-Sequenz im C-Terminus von Mic60 identifiziert, diese
zeigte einen Einfluss auf die Cristae-Stabilität. Zellen die eine Mic60-Variante mit einer
Deletion oder Punktmutation der ȕ- Domäne exprimieren, zeigten eine reduzierte Anzahl an
CJs. Auch das Verkürzen des C-Terminus von Mic60 hatte diesen Effekt auf die mitochondriale
Ultrastruktur. So konnte gezeigt werden, dass die ȕ-Domäne und die Integrität des C-Terminus
essentiell für die Stabilität von CJs sind.
Der Fokus dieser Arbeit lag in der Charakterisierung der MICOS-Komponenten Mic26
und Mic27. Es konnte bewiesen werden, dass beide Proteine genetisch mit der MICOSKernkomponente
Mic60 interagieren. Die Untersuchung der mitochondrialen Ultrastruktur von
Δmicβ6- und Δmicβ7-Zellen zeigte, dass eine Deletion vom Mic26 keinen Einfluss auf die
Organisation der mitochondrialen Innenmembran hat. Im Gegensatz dazu, ist im Vergleich zum
Wildtyp die Anzahl an CJs in Δmicβ7-Zellen um zwei Drittel reduziert. Auch die
Innenmembranoberfläche ist in diesen Zellen stark vergrößert. Die Untersuchung der
Morphologie der mitochondrialen Innenmembran in Zellen ohne Mic27 durch KryoElektronentomographie
isolierter Mitochondrien, veranschaulichte die Struktur der CJs in
diesen Zellen genauer. Es zeigten sich hier breitere CJs, und der Übergang von der
Cristaemembran in den Bereich der inneren Grenzmembran ist sehr flach und undefiniert. In
Wildtyp-Mitochondrien waren die CJs schmal und schlitzartig und haben einen scharfkantigen
Übergang von der Cristaemembran zur inneren Grenzmembran. Des Weiteren wies die
Cristaemembran in Δmicβ7-Zellen unregelmäßige zackige Strukturelemente auf, was auf eine
Anhäufung an Dimeren der F1FO-ATP Synthase hinweist.
Diese Beobachtungen in den Kryo-Tomogrammen, wurde durch Analysen des sich deutlich weniger höhere Oligomere und vermehrt Dimere. So kann aus diesen Befunden
geschlossen werden, dass Mic27 die Oligomere der F1FO-ATP Synthase stabilisiert.
Um zu untersuchen, wie der MICOS-Komplex mit der F1FO-ATP Synthase in
Verbindung steht, wurde mittels 2D-BNE-Analysen und einem Complexome Profiling die
Komplexierung der nativen Komplexe in Wildtyp- und Δmicβ7-Mitochondrien analysiert. Zum
einen konnte durch diese Untersuchungen gezeigt werden, dass Mic27 neben der F1FO-ATP
Synthase auch stabilisierend auf den MICOS-Komplex wirkt. Die Komplexe im
hochmolekularen Bereich der MICOS-Komponenten zerfielen in Δmicβ7-Zellen, was darauf
hinweist, dass die anderen MICOS-Komponenten hier nicht mehr assemblieren können. Mic10
war die einzige MICOS-Komponente die in Δmicβ7-Zellen noch stabile Komplexe im hohen
Massenbereich ausbildete. Mic10 findet sich zudem nicht nur in Klustern mit anderen MICOSKomponenten
sondern auch mit der F1FO-ATP Synthase.
Die Interaktion von Mic10 und der F1FO-ATP Synthase wurde auch biochemisch,
mittels chemischer Quervernetzern und Ko-Immunpräzipitationsexperimenten bestätigt. Dies
legt nahe, dass Mic10 die CJs mit hoher Wahrscheinlichkeit, durch die Verbindung mit der
F1FO-ATP Synthase, mit der Cristaemembran verbindet und so stabilisiert.
Aufgrund der Erkenntnisse dieser Arbeit konnte ein neuartiges Modell postuliert
werden. Die MICOS-Komponente Mic60 stabilisiert die CJs durch eine Interaktion seines CTerminus
mit Proteinen in der Außenmembran. Mic27 vermittelt über Mic10 die Interaktion
zur F1FO-ATP Synthase. Somit ist diese neu identifizierte Interaktion des MICOS-Komplex zur
F1FO-ATP Synthase essentiell für die Stabilität von CJs ist, indem es den MICOS-Komplex mit
den Oligomeren der F1FO-ATP Synthase verbindet.
Oligomerisierungszustands der F1FO-ATP Synthase in Δmicβ7-Zellen, bestätigt. Hier fanden
sich deutlich weniger höhere Oligomere und vermehrt Dimere. So kann aus diesen Befunden
geschlossen werden, dass Mic27 die Oligomere der F1FO-ATP Synthase stabilisiert.
Um zu untersuchen, wie der MICOS-Komplex mit der F1FO-ATP Synthase in
Verbindung steht, wurde mittels 2D-BNE-Analysen und einem Complexome Profiling die
Komplexierung der nativen Komplexe in Wildtyp- und Δmicβ7-Mitochondrien analysiert. Zum
einen konnte durch diese Untersuchungen gezeigt werden, dass Mic27 neben der F1FO-ATP
Synthase auch stabilisierend auf den MICOS-Komplex wirkt. Die Komplexe im
hochmolekularen Bereich der MICOS-Komponenten zerfielen in Δmicβ7-Zellen, was darauf
hinweist, dass die anderen MICOS-Komponenten hier nicht mehr assemblieren können. Mic10
war die einzige MICOS-Komponente die in Δmicβ7-Zellen noch stabile Komplexe im hohen
Massenbereich ausbildete. Mic10 findet sich zudem nicht nur in Klustern mit anderen MICOSKomponenten
sondern auch mit der F1FO-ATP Synthase.
Die Interaktion von Mic10 und der F1FO-ATP Synthase wurde auch biochemisch,
mittels chemischer Quervernetzern und Ko-Immunpräzipitationsexperimenten bestätigt. Dies
legt nahe, dass Mic10 die CJs mit hoher Wahrscheinlichkeit, durch die Verbindung mit der
F1FO-ATP Synthase, mit der Cristaemembran verbindet und so stabilisiert.
Aufgrund der Erkenntnisse dieser Arbeit konnte ein neuartiges Modell postuliert
werden. Die MICOS-Komponente Mic60 stabilisiert die CJs durch eine Interaktion seines CTerminus
mit Proteinen in der Außenmembran. Mic27 vermittelt über Mic10 die Interaktion
zur F1FO-ATP Synthase. Somit ist diese neu identifizierte Interaktion des MICOS-Komplex zur
F1FO-ATP Synthase essentiell für die Stabilität von CJs ist, indem es den MICOS-Komplex mit
den Oligomeren der F1FO-ATP Synthase verbindet.
Taxonomy, phylogeny and zoogeography of the hexaploid Torini of the Middle East and North Africa
(2017)
Fishes of the tribe Torini Karaman, 1971 (Teleostei: Cyprinidae) are a diverse group of primary freshwater fishes, distributed in Africa, the Middle East, and Indomalaya. They are an important component of the native freshwater-fish fauna of the Middle East and North Africa, and occur in most large river systems of the Levant, Arabia, Mesopotamia, southern Iran, and Morocco. They belong to the subfamily Cyprininae, are characterised by being tetraploid or hexaploid, having large scales, and a smooth and ossified last unbranched ray in the dorsal fin. As primary freshwater fishes they are not able to tolerate marine conditions and depend on direct freshwater connections for their dispersal. This makes them an ideal model for zoogeographic studies.
Prior to this study, the diversity of the Torini species in the Middle East and North Africa was not well understood. The validity of several genera and species was unclear, and the generic assignment of several species changed frequently.
In this PhD project the taxonomy, phylogeny, and zoogeography of the Torini of the Middle East and North Africa were investigated with morphological, as well as molecular methods. More than 1550 fish specimens were examined morphologically. Some of the specimens, including the types of most nominal species, were already available from museum collections. The remaining specimens were collected during expeditions to Ethiopia, Iran, Jordan, Morocco and Syria. Tissue samples were collected for molecular genetic analyses. The mitochondrial genes for cytochrome b, NADH dehydrogenase subunit 4 and the tRNAs for serine and histidine were sequenced from more than 120 specimens, representing 20 species of Torini and two small, diploid African barbs (Cyprinidae, tribe Smiliogastrini). Molecular data were analysed with Bayesian inference and other methods.
The analyses confirmed that the hexaploid Torini of Africa and the Middle East form a monophyletic group. In the Middle East and North Africa the Torini are represented by the genera Arabibarbus, Carasobarbus, Mesopotamichthys, and Pterocapoeta. These genera are each morphologically diagnosable, monophyletic, and genetically distinct. The species 'Labeobarbus' reinii cannot be assigned to any of these genera, because it is morphologically dissimilar and genetically clearly separated from each of them. A generic name for this species is presently not available and until the description of a new genus it is preliminarily assigned to the genus 'Labeobarbus'.
Out of the 28 species-group taxa described from the Middle East and North Africa until now, 15 are valid: Arabibarbus arabicus, A. grypus, A. hadhrami, Carasobarbus apoensis, C. canis, C. chantrei, C. exulatus, C. fritschii, C. harterti, C. kosswigi, C. luteus, C. sublimus, Mesopotamichthys sharpeyi, Pterocapoeta maroccana, and 'Labeobarbus' reinii.
The phylogenetic relationships between the Middle Eastern and North African Torini are well resolved, based on the analysis of mitochondrial DNA sequences from nearly all relevant species.
The interspecific and intraspecific morphological and genetic diversity is shaped by the zoogeographic history. Conclusions can be drawn about the events that shaped the evolution of this group. The Torini originated in the Indomalayan biogeographical realm and colonised the Middle East and Africa during the Miocene via the Gomphotherium landbridge. The Indomalayan Torini are tetraploid, whereas those of the Middle East and Africa are hexaploid. Molecular phylogenetic analyses showed that the hexaploid Torini cluster within the tetraploid Torini. This makes the tetraploid Torini a paraphyletic group with respect to the hexaploid Torini. Morocco was colonised in two independent waves. The first came from sub-Saharan Africa and is represented by Pterocapoeta maroccana. The second originated in the Middle East and gave rise to C. fritschii, C. harterti, and probably 'L.' reinii. The Tigris-Euphrates system is the largest freshwater system in the Middle East. Its central position between the Orontes River and Jordan River in the West, the Iranian tributaries to the Persian Gulf in the East, and the Arabian Peninsula in the South made it an important crossroad for the colonisation of the Middle East by Torini and other freshwater biota. During the Miocene the predecessors of the Jordan and Orontes rivers were connected to the Tigris-Euphrates system. The Jordan River was separated from the Euphrates before the Orontes. Arabia was colonised in two waves. The first (A. arabicus, A. hadhrami, C. exulatus) dates to the Pliocene, whereas the second (C. apoensis) ended as recently as the late Pleistocene or early Holocene.
Dieser Beitrag widmet sich der Hauptthese in Derek Parfits On What Matters, dass kantianische, konsequentialistische und kontraktualistische Theorien in der Moralphilosophie richtig verstanden zu gleichen Ergebnissen bei der Beurteilung moralischer Fragen gelangen. Anhand einer Diskussion von Parfits Reformulierung des kontraktualistischen Arguments wird gezeigt, dass die Akzeptanz dieser These entscheidend von einer Akzeptanz des Parfit’schen Gründebegriffs abhängt. Während es On What Matters nicht gelingen wird, diejenigen zu überzeugen, die Parfits objektiv-wertbasierte Gründetheorie nicht teilen, verweist selbst eine schwache Version der Konvergenzthese auf eine weitere wichtige Funktion des Moraldiskurses. Die von Parfit vorgestellte Objektivität und Einheit können dabei als notwendiges Element eines systematischen Moraldiskurses auftreten, der eine kontinuierliche Auseinandersetzung über universelle Normgehalte zum Inhalt hat.
According to international and national constitutional law, indigenous peoples in most Latin American countries have the right to maintain and strengthen their distinct political, legal, economic, social and cultural institutions. As a consequence of this and of a long and ongoing process of political debate and recognition, ever more indigenous peoples are practicing their own laws, following their own cultural traditions and customs. In doing so, they often draw on history, recreating their identities and reconstructing their distinct legal pasts. At the same time, historical research has increasingly pointed out the intense interaction between indigenous peoples and European invaders during colonial period. It has become clear that it is difficult to draw a clear line between purely ‘indigenous’ and ‘colonial’ legal traditions due to the hybridisation of indigenous and colonial laws and legal practices. The aim of this paper is to introduce this historiography and its relevance to law and to present some methodological challenges in writing the history of indigenous rights in Latin America resulting from this shift in (legal) historiography.
This article addresses concerns that the growth in global governance may be bringing with it a decline in the significance of democratic sources of political legitimacy. One approach in evaluating such concerns is to ask whether the respective patterns of legitimation for private and public authority differ or whether they refer to a similar set of normative standards. Private transnational governance regimes provide useful contexts in which to assess the presumed democratic erosion. They seem, almost of themselves, to make the case for such a decline: in them regulatory authority is exercised by non-state actors who, by their very nature, lack the kind of authorization afforded by the democratic procedures that legitimize state-based regulation; in addition, they are intrinsically linked to the notion of politics as a form of problem-solving rather than as the exercise of power. Given these characteristics, when governance arrangements of this kind are subjected to criticism, one would expect justificatory responses to relate primarily to performance, with normative criteria such as fundamental individual rights and the imperative for democratic procedure playing only a minor role. On the basis of a qualitative content analysis, the study tests three ideal-type patterns of legitimation for plausibility. The case selected for examination is the recent controversy surrounding the hybrid governance regime that operates to prevent the use of performance-enhancing drugs in sport. The debate offers the possibility of a ‘nutshell’ comparison of the respective patterns of legitimation used in criticizing and justifying state and non-state regulatory authority. This comparison yields two findings. The first is that the values used to appraise the state-based components of the sporting world’s hybrid regulatory regime do not differ systematically from those used to appraise the private elements: contestation and justification in both cases are founded on normative criteria relating to fundamental individual rights and democratic procedure and not just on performance-related considerations. The second finding is that justificatory grounds of the first type do not appear to be diminishing in importance vis-à-vis those of the second.
Corporatist regulation has a hybrid structure in that it covers state regulation, regulated self-regulation as well as private-public co-regulation. Notably diverging from the standard mode of state regulation, such arrangements required a higher degree of legitimation. Corporatist concepts flourished in the Weimar Republic. This paper deals with three legal scholars’ considerations regarding how to legitimize corporatist models, namely Edgar Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum. Their institutional touchstone was the Imperial Economic Council, as provided for by article 165 of the Weimar Constitution. This article envisioned a multi-level system of economic councils ranging from regional economic councils up to the Imperial Economic Council and involving representatives of all occupational groups in the performance of state tasks. However, only a Provisional Imperial Economic Council, with a restricted consultative remit, was ever actually established. Based on this model, Tatarin-Tarnheyden, Heinrich Herrfahrdt, and Friedrich Glum conceptualized organizational structures aiming at the comprehensive inclusion of non-state actors. They were legitimized primarily with reference to their output; that is, these organizational forms were supposed to enable a more appropriate and efficient realization of public interests. The input-based argument was basically a question of participation, which implies considerable proximity to typical topoi of democratic legitimation. This similarity is perhaps counter-intuitive, given that corporatist concepts are traditionally associated with anti-democratic ideologies due to their anti-parliamentarian slant. The numerous points of convergence between corporatist and democratic thought simultaneously reflect the heterogeneity of democratic reasoning in the Weimar period and the openness for ideas that were sceptical of—or even hostile to—parliamentary democracy and the party-based state.
This thematic issue brings together research from political science and legal history about legitimacy discourses covering different forms of public–private co-regulation and private self-regulation, domestic and transnational, past and present. These forms of governance highlight the important role of non-state actors in exercising public authority. There has been a growing debate about the legitimacy of non-state actors setting and enforcing norms and providing public goods and services. However, the focus of this thematic issue is not on developing abstract criteria of legitimacy. Rather, the authors analyze legitimacy discourses around different cases of privatized or partly privatized forms of governance from the early 20th century until today. Legitimacy is subject to empirical and not normative analysis. Legitimacy discourses are analyzed in order to shed light on the legitimacy conceptions that actors hold, what they consider as legitimate institutions, and based on what criteria. The particular focus of this thematic issue is to examine whether the significance of democratic legitimacy is decreasing as the importance of regulation exercised by private actors is increasing.
Die Reihe „Papers of Excellence 2.0: Ausgewählte Arbeiten aus den Fachdidaktiken und Bildungswissenschaften der Goethe-Universität Frankfurt a.M.“ ist eine neue, erweiterte und zusätzliche Auflage der bekannten Reihe „Papers of Excellence: Ausgewählte Arbeiten aus den Fachdidaktiken“, welche seit 2010 von Daniela Elsner und Anja Wildemann im Shaker-Verlag herausgegeben wird. In alter Tradition werden auch in der ab sofort zusätzlich zur Printausgabe erscheinenden Online Version dieser Buchreihe herausragende Examens- und Masterarbeiten, die sich durch eine ausgewiesene empirische, fachdidaktische Auseinandersetzung mit einem Thema auszeichnen, zusammenfassend vorgestellt. Neu ist, dass die Online Version nun auch Arbeiten mit einem bildungswissenschaftlichen Fokus aufnimmt und solche, die an der Schnittstelle zwischen Fachdidaktik und Bildungswissenschaften an-gelegt sind. Die Papers of Excellence 2.0, die derzeit nur Studien integriert, die an der Goethe Universität Frankfurt am Main angefertigt wurden, werden von Astrid Jurecka (Bildungswissenschaften) und Daniela Elsner (Fachdidaktik) herausgegeben und sind kostenfrei zugänglich.
Rezension zu Finn Fordham: I Do I Undo I Redo. The textual Genesis of Modernist Selves in Hopkins, Yeats, Conrad, Forster, Joyce, and Woolf. Oxford (Oxford University Press) 2010. 281 S.
"Why are not excrements, children and lice works of art?" fragt sich James Joyce 1903 in seinem Pariser Notizbuch. Im elf Jahre später fertig gestellten 'Portrait of the Artist as a Young Man' schreibt er die Frage Stephen Dedalus als Eintrag in dessen Notizbuch zu. Finn Fordhams Band 'I Do I Undo I Redo' verspricht, den Prozess der Verfertigung von Kunstwerken zu analysieren, der bei Joyce in Frage stehen bleibt.
Rezension zu Helga Thalhofer: 'Sans doute'. Die Ironie Prousts in Bezug auf die deutsche Frühromantik und Sören Kierkegaard. Heidelberg (Winter) 2010. 221 S.
Die zentrale These der Autorin ist, dass sich in Prousts Recherche du temps perdu Ironie auf allen Ebenen finde, wobei eine ideengeschichtliche Verortung diese umso deutlicher hervortreten lasse. Diese soll, wie Thalhofer in den einführenden Überlegungen expliziert, wesentlich über den Vergleich mit der Frühromantik und Sören Kierkegaard gelingen, die ihr als "Kontrastfolie" dienen.
Rezension zu Rüdiger Zymner (Hg.): Handbuch Gattungstheorie. Stuttgart, Weimar (Metzler) 2010. 368 S.
Es gibt Bücher, die man von vorne bis hinten lesen muss. Sammelbände zählen nicht dazu; Lexika noch weniger: sie folgen einer Ordnung, die der Sache ganz äußerlich ist. Und Handbücher? Im Unterschied zu Lexika, die ihren Gegenstand profilieren, indem sie die alphabetisch geordneten Begriffe durch eine Hyperlink-Struktur dicht vernetzen, sind diese nicht nur dazu gedacht, ihren Gegenstand begrifflich zu erschließen, sondern ihn auch systematisch zu präsentieren. Handbücher wollen nicht nur gelegentlich zur Hand genommen werden, sie zielen auch darauf ab, alles, was man wissen und bedacht haben sollte, in handlichem Format darzustellen. Die hier zu besprechende Publikation erfüllt diese Ansprüche auf mustergültige Weise.
Rezension zu Jörn Steigerwald u. Rudolf Behrens (Hg.): Räume des Subjekts um 1800. Zur imaginativen Selbstverortung des Individuums zwischen Spätaufklärung und Romantik. Wiesbaden (Harrassowitz) 2010. 286 S.
Der aus der gleichnamigen Tagung 2007 in Bochum hervorgegangene Sammelband zu Subjektentwürfen und deren Raumbezug respektive dessen Erfahrung und Konzeptionierung versammelt mit romanistischem Schwerpunkt zwölf einander ergänzende Beiträge.
[Rezension zu:] Norbert Bachleitner und Michaela Wolf (Hg.): Streifzüge im translatorischen Feld
(2012)
Rezension zu Norbert Bachleitner und Michaela Wolf (Hg.): Streifzüge im translatorischen Feld. Zur Soziologie der literarischen Ubersetzung im deutschsprachigen Raum. Wien (LIT) 2010 (= Repräsentation - Transformation, Bd. 5), 372 S.
Vorliegender Sammelband stellt eine Aktualisierung und Erweiterung des sechs Aufsätze umfassenden, ebenfalls von den Herausgebern besorgten Themenhefts "Soziologie der literarischen Übersetzung" im Internationalen Archiv für Sozialgeschichte der deutschen Literatur 29, Bd. 2 (2004) dar. Drei Beiträge aus dem Themenheft wurden in überarbeiteter Fassung in die Buchpublikation übernommen, neu hinzugekommen sind elf Aufsätze und drei Interviews mit übersetzenden SchriftstellerInnen.
Tagungsbericht: Playing False : representations of Betrayal
16. bis 17. September 2011, Lincoln College, Oxford University
From antiquity through the present, from the political sphere to the most personal relationships, betrayal is a ubiquitous and multifaceted phenomenon. Because of its many forms, however, betrayal demands an intensive examination within an interdisciplinary forum that transcends the narrower, political or literary spheres of betrayal, and that strives to address the multiplicity of its representations, rather than reducing it to a single definition. It is precisely such a forum that the conference, "Playing False: Representations of Betrayal" created, which Dr. Betiel Wasihun and Kristina Mendicino organized.
Mimesis
(2012)
Tagungsbericht zum Jubiläumssymposium des Promotionsstudiengangs Literaturwissenschaft der Ludwig-Maximilians-Universität München, Kloster Seeon, 29. bis 31. Juli 2011.
Wie stellt die Kunst Wirklichkeit dar? Um welche Auffassung von Kunst (Literatur, bildende Kunst, Musik), um welche von Wirklichkeit (Welt, Natur, Schöpfung) handelt es sich? Um diese Fragen kreist der Begriff der Mimesis. Der 'Promotionsstudiengang Literaturwissenschaft' feierte im Juli 2011 in Kloster Seeon sein zehnjähriges Bestehen mit einem Jubiläumssymposium, das Perspektiven auf diese äußerst vielschichtige, historisch wandelbare Kategorie der Ästhetik und Poetik öffnete.
Background: The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text.
Results: We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities.
Conclusions: The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established vocabularies or ontologies, but rather serve as an overarching framework based on which different application- and domain-specific ontologies, thesauri and vocabularies of phenotypes observed in flowering plants can be integrated.
Katastrophen
(2012)
Tagungsbericht zum 2. Interdisziplinären Symposium des Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-Universität Freiburg, 4. bis 6. Mai 2011.
Katastrophen erscheinen im Lichte der Berichterstattung über das Erdbeben, den Tsunami und den Reaktorunfall in Japan allgegenwärtig zu sein. Tatsächlich wird jede (aufgeklärte) Gesellschaft durch den Zusammenbruch der Ordnung in Form verheerender Unglücke bedroht, die nicht mehr durch eine transzendente Instanz erklärt und aufgefangen werden können. Allerdings können solche Ereignisse gleichzeitig als Motor fur Entwicklung und Fortschritt fungieren. Diese ambivalente Bedeutung des Begriffs sowie der akuten "Katastrophe" war Thema des 2. Interdisziplinären Symposiums des 'Freiburg Institute for Advanced Studies' (FRIAS) im Mai 2011.
The Escherichia coli sensor kinase EnvZ modulates porin expression in response to various stimuli, including extracellular osmolarity, the presence of procaine and interaction with an accessory protein, MzrA. Two major outer membrane porins, OmpF and OmpC, act as passive diffusion-limited pores that allow compounds, including certain classes of antibiotics such as β-lactams and fluoroquinolones, to enter the bacterial cell. Even though the mechanisms by which EnvZ detects and processes the presence of various stimuli are a fundamental component of microbial physiology, they are not yet fully understood. Here, we assess the role of TM1 during signal transduction in response to the presence of extracellular osmolarity. Various mechanisms of transmembrane communication have been proposed including rotation of individual helices within the transmembrane domain, dynamic movement of the membrane-distal portion of the cytoplasmic domain and regulated intra-protein unfolding. To assess these possibilities, we have created a library of single-Cys-containing EnvZ proteins in order to facilitate sulfhydryl-reactivity experimentation. Our results demonstrate that the major TM1-TM1' interface falls along a single surface consisting of residue positions 19, 23, 26, 30 and 34. In addition, we show that Cys substitutions within the N- and C-terminal regions of TM1 result in drastic changes to EnvZ signal output. Finally, we demonstrate that core residues within TM1 are responsible for both TM1 dimerisation and maintenance of steady-state signal output. Overall, our results suggest that no major rearrangement of the TM1-TM1' interface occurs during transmembrane communication in response to extracellular osmolarity. We conclude by discussing these results within the frameworks of several proposed models for transmembrane communication.
Objective: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.
Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.
Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks.
Conclusion: The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts.
The Gram-negative bacteria Photorhabdus and Xenorhabdus are known to produce a variety of different natural products (NP). These compounds play different roles since the bacteria live in symbiosis with nematodes and are pathogenic to insect larvae in the soil. Thus, a fine tuned regulatory system controlling NP biosynthesis is indispensable. Global regulators such as Hfq, Lrp, LeuO and HexA have been shown to influence NP production of Photorhabdus and Xenorhabdus. Additionally, photopyrones as quorum sensing (QS) signals were demonstrated to be involved in the regulation of NP production in Photorhabdus. In this study, we investigated the role of another possible QS signal, autoinducer-2 (AI-2), in regulation of NP production. The AI-2 synthase (LuxS) is widely distributed within the bacterial kingdom and has a dual role as a part of the activated methyl cycle pathway, as well as being responsible for AI-2 precursor production. We deleted luxS in three different entomopathogenic bacteria and compared NP levels in the mutant strains to the wild type (WT) but observed no difference to the WT strains. Furthermore, the absence of the small regulatory RNA micA, which is encoded directly upstream of luxS, did not influence NP levels. Phenotypic differences between the P. luminescens luxS deletion mutant and an earlier described luxS deficient strain of P. luminescens suggested that two phenotypically different strains have evolved in different laboratories.
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
Bücherschau
(2001)
Am 25. April verstarb im 75. Lebensjahr nach langer schwerer Krankheit Gisbert Große-Brauckmann. In Göttingen am 12. Mai 1926 geboren, wuchs er in einem durch die Altphilologie geprägten Elternhaus auf. Vater und Großvater waren Altphilologen; dennoch zeigte sich schon früh das besondere Interesse von Gisbert Große-Brauckmann für die Biologie und insbesondere die Botanik.
Biodiversität und nachhaltige Entwicklung sind Leitziele zukünftigen Handelns in der Landschaft. Auf der Ebene der Vegetation heißt dies: Wie kann die größtmögliche Vielfalt von Pflanzengesellschaften in einer Region erhalten und entwickelt werden? Wie können diese Gesellschaften in eine nachhaltige Landbewirtschaftung integriert werden? Wie kann die Vegetation überhaupt wieder stärker in die Kulturtätigkeit des Menschen eingebunden werden? Das Konzept der Potentiellen Kulturlandschafts-Vegetation ist der Versuch einer Antwort auf diese Fragen. Es wird dem Konzept der potentiellen natürlichen Vegetation gegenübergestellt, indem es bewußt den Menschen in den Mittelpunkt der Betrachtung rückt. Die Potentielle Kulturlandschafts-Vegetation (PKV) ist demnach diejenige Vegetation, die sich in einem Landschaftsraum gerade durch die qualitativ unterschiedlichen Tätigkeiten des Menschen entwickelt. Dabei werden vor allem diejenigen Tätigkeiten ins Auge gefaßt, die die Vielfalt von Vegetationstypen erhöhen. Bei der Ordnung der Vegetation nach Hemerobiegraden ist ebenfalls der Mensch der Bezugspunkt. Dieses Verfahren hat jedoch den Nachteil, daß das mehrdimensionale Nutzungsmuster der Tätigkeiten des Menschen auf eine eindimensionale Skala reduziert wird. Das Konzept der Potentiellen Kulturlandschafts-Vegetation versucht dagegen, die mehrdimensionale Ordnung menschlichen Wirkens abzubilden. Dazu wird die historische Einheit von Dorf und Dorfgemarkung zugrundegelegt. An Beispielen von Grünland-Vegetationskomplexen aus den nordwestdeutschen Geest- und Lößlandschaften wird die PKV des dörflichen Kulturgradienten sigmasoziologisch dargestellt und damit das anthropogene Vegetationspotential der verschiedenen, nutzungsbedingten Zonen herausgearbeitet. Die Begrenztheit dieses Verfahrens unter den Bedingungen der heutigen ausgeräumten Landschaften wird diskutiert und auf die Notwendigkeit der zusätzlichen Auswertung historischer Quellen hingewiesen. Die Bedeutung der Magerrasen innerhalb der PKV wird herausgestellt. Abschließend wird die Anwendungsmöglichkeit des Konzeptes der PKV für die Landschaftsentwicklung aufgezeigt.
Woher rührt das besondere Interesse der Argentinier an dem Stoff über die Geschwister Elektra und Orest, die den Mord am rechtmäßigen König Agamemnon, ihrem Vater, nicht dulden wollen, zu Muttermördern werden und sich am Ende einem Gericht stellen müssen? Im folgenden Beitrag wird argumentiert, dass dem politischen Theater in zwei sehr verschiedenen Zeiträumen eine vergleichbar wichtige, politikrelevante Bedeutung zukommt: in der politischen und gesellschaftlichen Umbruchsituation zur Entstehungszeit der Orestie, während des Wandels von der Aristokratie zur Demokratie, und zur Entstehungszeit moderner argentinischer Elektra-Adaptionen, in der Aufbereitung diktatorischer Vergangenheit. Der Elektra-Stoff erweist sich als zentraler Verhandlungsort politischer Legitimation und diskutiert in der Gegenüberstellung zweier widerstreitender Ordnungen Möglichkeitsbedingungen der Konfliktbeilegung.
Plantago coronopus subsp. commutata (GUSS.) PILGER, eine im zentral- bis ostmediterranen Küstenraum beheimatete Unterart des halophilen Schlitzblatt-Wegerichs, konnte erstmalig als eingebürgerter Straßenrandhalophyt im südlichen Bayern bei Mittenwald (Deutschland) und im nördlichen Teil Tirols (Österreich) nachgewiesen werden. Die ermittelten Vorkommen, die Ökologie der Art und ihr möglicher Ausbreitungsweg werden diskutiert. Die diagnostischen Merkmale zur Unterscheidung dieser Unterart von der Nominatsippe P. coronopus subsp. coronopus werden erläutert.
Auf der Ebene von Formationen und Vegetationsklassen wird eine Übersicht über die pflanzensoziologische Verbreitung der rund 565 einheimischen und eingebürgerten Annuellen basierend auf ROTHMALER et al. (1996) gegeben. Annuelle kommen in 12 der 13 Formationen (sensu WILMANNS 1998) vor. Die Untersuchung gibt ferner einen Überblick, welche der insgesamt zwanzig Wuchsformen Annueller in den einzelnen Gesellschaftsklassen in welchem Umfang vertreten sind. Es werden Bezüge zwischen der Vergesellschaftung der einzelnen Art und ihrer Wuchsform in Hinblick auf den Anpassungswert morphologischer Merkmale herausgestellt. Während phänotypisch plastische (aktive) Anpassungserscheinungen sehr selten sind, kommen familientypische, d.h. systematische, genotypische Merkmale, die als (passive) Vorteile für die Art betrachtet werden können, weit häufiger vor. Die Hypothese, daß morphologisch bzw. physiologisch spezialisierte Arten (Klettern, Sukkulenz, Parasitismus) eine geringe soziologische Amplitude besitzen, d.h. in nur wenigen Verbänden/Klassen vergesellschaftet sind, bzw. daß morphologisch unspezifischere Arten eine weite Amplitude besitzen, konnte nur zum Teil bestätigt werden. Mit einigen Ausnahmen sind die Arten der unterschiedlichen Wuchsformgruppen in durchschnittlich 1,5-1,8 Vegetationsklassen vergesellschaftet. Etwa 43% der Annuellen sind indigen, 31% gehören zu den Archäophyten und 26% zu den Neophyten. Als agriophytisch sind 57 Arten einzustufen, was ca. der Hälfte aller Agriophyten in Mitteleuropa entspricht.
Im atlantischen und in zentralen Teil Mitteleuropas erweisen sich Plantago major, Poa annua, Polygonum arenastrum und Matricaria discoidea als der Kern der Gruppe der Trittpflanzengesellschaften. Die Zusammenfassung aller Gesellschaften, in denen eine oder mehrere dieser Arten gemeinsam dominieren, zu einer Klasse, nämlich den Plantaginetea majoris, ist unter den zahlreichen momentan in der Literatur verwirklichten Wegen der Syntaxonomie der Trittpflanzengesellschaften derjenige, der am besten sowohl mit der Lehre der Charakterarten nach BRAUN-BLANQUET als auch mit den Gegebenheiten im Gelände übereinstimmt und zudem keinerlei logische Widersprüche in sich aufweist. Die Tatsache, daß Plantago major im kontinentalen Bereich Mitteleuropas und im übrigen Gebiet lokal an Trockenstandorten gegenüber den einjährigen Arten zurücktritt, spricht nicht gegen eine solche Lösung. Das Zentrum der Klasse der Trittpflanzengesellschaften muß nämlich dort liegen, wo Tritt der entscheidende, möglichst sogar der alleinige Auslesefaktor ist, und nicht dort, wo länger andauernde Phasen von Trockenheit als weiterer Auslesefaktor hinzukommen.
Messungen morphologischer Parameter an Potamogetón perfoliatus führten zu zahlreichen positiven Korrelationen wie bereits frühere Untersuchungen an Isoëtes lacustris. Es ergaben sich Übereinstimmungen trotz unterschiedlicher Lebensgeschichte. Abweichungen spiegeln die unterschiedlichen Wachstumsstrategien wider, die die beiden Arten verfolgen. Weitere Korrelationen zeigen die Abhängigkeit der Blattentwicklung bei P. perfoliatus bzw. der Rosettenausbildung bei I. lacustris von Standortbedingungen. Ergänzende Messungen erwiesen, dass eine Reihe von Regressionsgleichungen für weitere 6 Laichkrautarten bzw. 9 Isoëtes-Taxa gültig ist. Ihre besondere Bedeutung haben die erhaltenen Regressionsgleichungen für die zerstörungsfreie Gewinnung von Daten für gefährdete Pflanzenarten und ihre Bestände, beispielsweise den Blattflächenindex; dafür werden Beispiele gegeben.
Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤1:10 before and ≥1:40 after or ≥1:10 before and ≥4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.
Background: High-dimensional biomedical data are frequently clustered to identify subgroup structures pointing at distinct disease subtypes. It is crucial that the used cluster algorithm works correctly. However, by imposing a predefined shape on the clusters, classical algorithms occasionally suggest a cluster structure in homogenously distributed data or assign data points to incorrect clusters. We analyzed whether this can be avoided by using emergent self-organizing feature maps (ESOM).
Methods: Data sets with different degrees of complexity were submitted to ESOM analysis with large numbers of neurons, using an interactive R-based bioinformatics tool. On top of the trained ESOM the distance structure in the high dimensional feature space was visualized in the form of a so-called U-matrix. Clustering results were compared with those provided by classical common cluster algorithms including single linkage, Ward and k-means.
Results: Ward clustering imposed cluster structures on cluster-less "golf ball", "cuboid" and "S-shaped" data sets that contained no structure at all (random data). Ward clustering also imposed structures on permuted real world data sets. By contrast, the ESOM/U-matrix approach correctly found that these data contain no cluster structure. However, ESOM/U-matrix was correct in identifying clusters in biomedical data truly containing subgroups. It was always correct in cluster structure identification in further canonical artificial data. Using intentionally simple data sets, it is shown that popular clustering algorithms typically used for biomedical data sets may fail to cluster data correctly, suggesting that they are also likely to perform erroneously on high dimensional biomedical data.
Conclusions: The present analyses emphasized that generally established classical hierarchical clustering algorithms carry a considerable tendency to produce erroneous results. By contrast, unsupervised machine-learned analysis of cluster structures, applied using the ESOM/U-matrix method, is a viable, unbiased method to identify true clusters in the high-dimensional space of complex data.
Graphical abstract: 3-D representation of high dimensional data following ESOM projection and visualization of group (cluster) structures using the U-matrix, which employs a geographical map analogy of valleys where members of the same cluster are located, separated by mountain ranges marking cluster borders.
Correlation of lumbar lateral recess stenosis in magnetic resonance imaging and clinical symptoms
(2017)
Aim: To assess the correlation of lateral recess stenosis (LRS) of lumbar segments L4/5 and L5/S1 and the Oswestry Disability Index (ODI).
Methods: Nine hundred and twenty-seven patients with history of low back pain were included in this uncontrolled study. On magnetic resonance images (MRI) the lateral recesses (LR) at lumbar levels L4/5 and L5/S1 were evaluated and each nerve root was classified into a 4-point grading scale (Grade 0-3) as normal, not deviated, deviated or compressed. Patient symptoms and disability were assessed using ODI. The Spearman’s rank correlation coefficient was used for statistical analysis (P < 0.05).
Results: Approximately half of the LR revealed stenosis (grade 1-3; 52% at level L4/5 and 42% at level L5/S1) with 2.2% and 1.9% respectively reveal a nerve root compression. The ODI score ranged from 0%-91.11% with an arithmetic mean of 34.06% ± 16.89%. We observed a very weak statistically significant positive correlation between ODI and LRS at lumbar levels L4/5 and L5/S1, each bilaterally (L4/5 left: rho < 0.105, P < 0.01; L4/5 right: rho < 0.111, P < 0.01; L5/S1 left: rho 0.128, P < 0.01; L5/S1 right: rho < 0.157, P < 0.001).
Conclusion: Although MRI is the standard imaging tool for diagnosing lumbar spinal stenosis, this study showed only a weak correlation of LRS on MRI and clinical findings. This can be attributed to a number of reasons outlined in this study, underlining that imaging findings alone are not sufficient to establish a reliable diagnosis for patients with LRS.
Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins. The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown. By combining an in vitro mitochondrial fusion assay with electron cryo-tomography (cryo-ET), we visualize the junction between attached mitochondria isolated from Saccharomyces cerevisiae and observe complexes that mediate this attachment. We find that cycles of GTP hydrolysis induce progressive formation of a docking ring structure around extended areas of contact. Further GTP hydrolysis triggers local outer membrane fusion at the periphery of the contact region. These findings unravel key features of mitofusin-dependent fusion of outer membranes and constitute an important advance in our understanding of how mitochondria connect and merge.
Microtubule-targeting agents (MTAs) are the most widely used chemotherapeutic drugs. Pretubulysin (PT), a biosynthetic precursor of the myxobacterial tubulysins, was recently identified as a novel MTA. Besides its strong anti-tumoral activities, PT attenuates tumor angiogenesis, exerts anti-vascular actions on tumor vessels and decreases cancer metastasis formation in vivo. The aim of the present study was to analyze the impact of PT on the interaction of endothelial and tumor cells in vitro to gain insights into the mechanism underlying its anti-metastatic effect. The influence of PT on tumor cell adhesion and transmigration onto/through the endothelium as well as its influence on cell adhesion molecules and the chemokine system CXCL12/CXCR4 was investigated. Treatment of human endothelial cells with PT increased the adhesion of breast cancer cells to the endothelial monolayer, whereas their transmigration through the endothelium was strongly reduced. Interestingly, the PT-induced upregulation of ICAM-1, VCAM-1 and CXCL12 were dispensable for the PT-evoked tumor cell adhesion. Tumor cells preferred to adhere to collagen exposed within PT-triggered endothelial gaps via β1-integrins on the tumor cell surface. Taken together, our study provides, at least in part, an explanation for the anti-metastatic potential of PT.
The effects of acute physical exercise on memory, peripheral BDNF, and cortisol in young adults
(2016)
In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans.
Background: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF.
Methods: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1–2 h infusion of 500–2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed.
Results: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized.
Conclusions: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses.
Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476)
Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complex membrane protein complexes. The enzyme contributes substantially to oxidative energy-conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. Here, we report the X-ray structure of mitochondrial complex I at 3.6- 3.9 Å resolution describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the ‘deactive’ form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site rendering support for a two-state stabilization-change mechanism of protonpumping.
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome‐guided pre‐clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.