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Scheckhuber, Christian Quintus ; Grief, Jürgen ; Boilan, Emmanuelle ; Luce, Karin ; Debacq-Chainiaux, Florence ; Rittmeyer, Claudia ; Gredilla, Ricardo ; Kolbesen, Bernd O. ; Toussaint, Olivier ; Osiewacz, Heinz D.
In previous investigations an impact of cellular copper homeostasis on ageing of the ascomycete Podospora anserina has been demonstrated. Here we provide new data indicating that mitochondria play a major role in this process. Determination of copper in the cytosolic fraction using total reflection X-ray fluorescence spectroscopy analysis and eGfp reporter gene studies indicate an age-related increase of cytosolic copper levels. We show that components of the mitochondrial matrix (i.e. eGFP targeted to mitochondria) become released from the organelle during ageing. Decreasing the accessibility of mitochondrial copper in P. anserina via targeting a copper metallothionein to the mitochondrial matrix was found to result in a switch from a copper-dependent cytochrome-c oxidase to a copper-independent alternative oxidase type of respiration and results in lifespan extension. In addition, we demonstrate that increased copper concentrations in the culture medium lead to the appearance of senescence biomarkers in human diploid fibroblasts (HDFs). Significantly, expression of copper-regulated genes is induced during in vitro ageing in medium devoid of excess copper suggesting that cytosolic copper levels also increase during senescence of HDFs. These data suggest that the identified molecular pathway of age-dependent copper dynamics may not be restricted to P. anserina but may be conserved from lower eukaryotes to humans.
Plasticity resembling spike-timing dependent synaptic plasticity: the evidence in human cortex
(2010)
Spike-timing dependent plasticity (STDP) has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behavior such as learning and memory. Keywords: spike-timing dependent plasticity, long-term potentiation, long-term depression, paired associative stimulation, transcranial magnetic stimulation, human, cortex, translational neuroscience
Ivanova, Elena V. ; Volk, C.-Michael ; Riediger, Oliver ; Klein, Holger ; Sitnikov, Nikolay ; Ulanovskii, Alexey ; Yushkov, Vladimir ; Ravegnani, Fabrizio ; Möbius, Tanja ; Schmidt, Ulrich
In order to quantitatively analyse the chemical and dynamical evolution of the polar vortex it has proven extremely useful to work with coordinate systems that follow the vortex flow. We propose here a two-dimensional quasi-Lagrangian coordinate system {X i, delta X i}, based on the mixing ratio of a long-lived stratospheric trace gas i, and its systematic use with i = N2O, in order to describe the structure of a well-developed Antarctic polar vortex. In the coordinate system {X i, delta X i} the mixing ratio X i is the vertical coordinate and delta X i = X i(theta) - X i vort(theta) is the meridional coordinate (X i vort(theta) being a vertical reference profile in the vortex core). The quasi-Lagrangian coordinates {X i, delta X i} persist for much longer time than standard isentropic coordinates, potential temperature theta and equivalent latitude Phi e, do not require explicit reference to geographic space, and can be derived directly from high-resolution in situ measurements. They are therefore well-suited for studying the evolution of the Antarctic polar vortex throughout the polar winter with respect to the relevant chemical and microphysical processes. By using the introduced coordinate system {X N2O, delta X N2O} we analyze the well-developed Antarctic vortex investigated during the APE-GAIA (Airborne Polar Experiment – Geophysica Aircraft in Antarctica – 1999) campaign (Carli et al., 2000). A criterion, which uses the local in-situ measurements of X i=X i(theta) and attributes the inner vortex edge to a rapid change (delta-step) in the meridional profile of the mixing ratio X i, is developed to determine the (Antarctic) inner vortex edge. In turn, we suggest that the outer vortex edge of a well-developed Antarctic vortex can be attributed to the position of a local minimum of the X H2O gradient in the polar vortex area. For a well-developed Antarctic vortex, the delta X N2O-parametrization of tracer-tracer relationships allows to distinguish the tracer inter-relationships in the vortex core, vortex boundary region and surf zone and to examine their meridional variation throughout these regions. This is illustrated by analyzing the tracer-tracer relationships X i : X N2O obtained from the in-situ data of the APE-GAIA campaign for i = CFC-11, CFC-12, H-1211 and SF6. A number of solitary anomalous points in the CFC-11 : N2O correlation, observed in the Antarctic vortex core, are interpreted in terms of small-scale cross-isentropic dispersion.
Potentiation of glycine-gated NR1/NR3A NMDA receptors relieves Ca2+-dependent outward rectification
(2010)
Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs) and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA) receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named “excitatory glycine receptors”. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I–V) dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I–V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM) present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I–V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors. Keywords: NMDA receptor, excitatory glycine receptor, voltage block, NR3 subunit, supralinear potentiation, Zn2+, NR1 antagonist, ligand-binding domain
Although models based on independent component analysis (ICA) have been successful in explaining various properties of sensory coding in the cortex, it remains unclear how networks of spiking neurons using realistic plasticity rules can realize such computation. Here, we propose a biologically plausible mechanism for ICA-like learning with spiking neurons. Our model combines spike-timing dependent plasticity and synaptic scaling with an intrinsic plasticity rule that regulates neuronal excitability to maximize information transmission. We show that a stochastically spiking neuron learns one independent component for inputs encoded either as rates or using spike-spike correlations. Furthermore, different independent components can be recovered, when the activity of different neurons is decorrelated by adaptive lateral inhibition.
Understanding the dynamics of recurrent neural networks is crucial for explaining how the brain processes information. In the neocortex, a range of different plasticity mechanisms are shaping recurrent networks into effective information processing circuits that learn appropriate representations for time-varying sensory stimuli. However, it has been difficult to mimic these abilities in artificial neural network models. Here we introduce SORN, a self-organizing recurrent network. It combines three distinct forms of local plasticity to learn spatio-temporal patterns in its input while maintaining its dynamics in a healthy regime suitable for learning. The SORN learns to encode information in the form of trajectories through its high-dimensional state space reminiscent of recent biological findings on cortical coding. All three forms of plasticity are shown to be essential for the network's success. Keywords: synaptic plasticity, intrinsic plasticity, recurrent neural networks, reservoir computing, time series prediction
We examined whether positive transfer of cognitive training, which so far has been observed for individual tests only, also generalizes to cognitive abilities, thereby carrying greater promise for improving everyday intellectual competence in adulthood and old age. In the COGITO Study, 101 younger and 103 older adults practiced six tests of perceptual speed (PS), three tests of working memory (WM), and three tests of episodic memory (EM) for over 100 daily 1-h sessions. Transfer assessment included multiple tests of PS, WM, EM, and reasoning. In both age groups, reliable positive transfer was found not only for individual tests but also for cognitive abilities, represented as latent factors. Furthermore, the pattern of correlations between latent change factors of practiced and latent change factors of transfer tasks indicates systematic relations at the level of broad abilities, making the interpretation of effects as resulting from unspecific increases in motivation or self-concept less likely. Keywords: cognitive training, cognitive abilities, transfer, latent factors, working memory
Disruptive behaviour disorders are reflected by a great variety of symptoms ranging from impulsive-hot tempered quarrels to purposeful and goal directed acts of cruelty. A growing body of data indicates that there are neurobiological factors that increase the risk for developing disruptive behaviour disorders. In this review, we give a broad overview of recent studies investigating physiological, neural, genetic factors, and specific neurotransmitter systems. We also discuss the impact of psychosocial risk and consider the effects of gene-environment interactions. Due to the heterogeneity of disruptive behaviour disorders, it is concluded that specific subtypes of disruptive behaviour should be considered both in terms their biological basis and in regard to specific treatment needs.
Schootbrugge, Bas van de ; Harazim, Dario ; Sorichter, Katrin ; Oschmann, Wolfgang ; Fiebig, Jens ; Püttmann, Wilhelm ; Peinl, Mark ; Zanella, Friedhelm ; Teichert, Barbara M. A. ; Hoffmann, J. ; Stadnitskaia, Alina ; Rosenthal, Yair
Tubular carbonate concretions of up to 1 m in length and perpendicular to bedding, occur abundantly in the Upper Pliensbachian (upper Amaltheus margaritatus Zone, Gibbosus Subzone) in outcrops (Fontaneilles section) in the vicinity of Rivière-sûr-Tarn, southern France. Stable isotope analyses of these concretions show negative delta 13C values that decrease from the rim to the center from - 18.8‰ to - 25.7‰ (V-PDB), but normal marine delta 18 O values (- 1.8‰). Carbon isotope analyses of Late Pliensbachian bulk carbonate (matrix) samples from the Fontaneilles section show clearly decreasing C-isotope values across the A. margaritatus Zone, from +1‰ to - 3‰ (V-PDB). Isotope analyses of coeval belemnite rostra do not document such a negative C-isotope trend with values remaining stable around +2‰ (V-PDB). Computer tomographic (CT) scanning of the tubular concretions show multiple canals that are lined or filled entirely with pyrite. Previously, the formation of these concretions with one, two, or more central tubes, has been ascribed to the activity of an enigmatic organism, possibly with annelid or arthropod affinities, known asTisoa siphonalis. Our results suggest tisoan structures are abiogenic. Based on our geochemical analyses and sedimentological observations we suggest that these concretions formed as a combination of the anaerobic oxidation of methane (AOM) and sulfate reduction within the sediment. Fluids rich in methane and/or hydrocarbons likely altered local bulk rock carbon isotope records, but did not affect the global carbon cycle. Interestingly, Tisoa siphonalis has been described from many locations in the Grands Causses Basin in southern France, and from northern France and Luxemburg, always occurring at the same stratigraphic level. Upper Pliensbachian authigenic carbonates thus possibly cover an area of many thousand square kilometers. Greatly reduced sedimentation rates are needed to explain the stabilization of the sulfate-methane transition zone in the sedimentary column in order for the tubular concretions to form. Late Pliensbachian cooling, reducing run-off, and/or the influx of colder water and more vigorous circulation could be responsible for a halt in sedimentation. At the same time (thermogenic) methane may have destabilized during a major phase of Late Pliensbachian sea level fall. As such Tisoa siphonalis is more than a geological curiosity, and its further study could prove pivotal in understanding Early Jurassic paleoenvironmental change.
Cerveira, Nuno ; Meyer, Claus ; Santos, Joana ; Torres, Lurdes ; Lisboa, Susana ; Pinheiro, Manuela ; Bizarro, Susana ; Correia, Cecilia ; Norton, Lucilia ; Marschalek, Rolf ; Teixeira, Manuel R.
Background: Abnormalities of 11q23 involving the MLL gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia. Methods: Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the CT45A2 gene as novel MLL fusion partner in pediatric acute leukemia. Results: Fluorescence in situ hybridization of the patient G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the MLL gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing MLL exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the CT45A2 gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the DDX26B gene (exons 9-16) and the entire CT45A1 gene was identified. RNA analysis revealed the presence of a novel MLL-CT45A2 fusion transcript in which the first 9 exons of the MLL gene were fused in-frame to exon 2 of the CT45A2 gene, resulting in a spliced MLL fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE/L1 and SINE/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences. Conclusion: We have identified CT45A2 as a novel spliced MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since CT45A2 is the first Cancer/Testis antigen family gene found fused with MLL in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted.
Wagener, Nina ; Macher-Göppinger, Stephan ; Pritsch, Maria ; Hüsing, Johannes ; Hoppe-Seyler, Karin ; Schirmacher, Peter ; Pfitzenmaier, Jesco ; Haferkamp, Axel ; Hoppe-Seyler, Felix ; Hohenfellner, Markus
Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.
Blagosklonny, Mikhail V. ; Campisi, Judy ; Sinclair, David A. ; Bartke, Andrzej ; Blasco, Maria A. ; Bonner, William M. ; Bohr, Vilhelm A. ; Brosh, Robert M. ; Brunet, Anne ; DePinho, Ronald A. ; Donehower, Lawrence A. ; Finch, Caleb E. ; Finkel, Toren ; Gorospe, Myriam ; Gudkov, Andrei V. ; Hall, Michael N. ; Hekimi, Siegfried ; Helfand, Stephen L. ; Karlseder, Jan ; Kenyon, Cynthia ; Kroemer, Guido ; Longo, Valter ; Nussenzweig, Andre ; Osiewacz, Heinz D. ; Peeper, Daniel S. ; Rando, Thomas A. ; Rudolph, K. Lenhard ; Sassone-Corsi, Paolo ; Serrano, Manuel ; Sharpless, Norman E. ; Skulachev, Vladimir P. ; Tilly, Jonathan L. ; Tower, John ; Verdin, Eric ; Vijg, Jan
The editorial board of Aging reviews research papers published in 2009,which they believe have or will have a significant impact on aging research.Among many others, the topics include genes that accelerate aging or incontrast promote longevity in model organisms, DNA damage responsesand telomeres, molecular mechanisms of life span extension by calorierestriction and pharmacologic interventions into aging. The emergingmessage in 2009 is that aging is not random but determined by agenetically-regulated longevity network and can be decelerated bothgenetically and pharmacologically.
Germany’s educational system has undergone a series of transformations during the last 40 years. In recent years, marked increases in enrolment have occurred. In response, admission requirements have been relaxed and new universities have been established. Academic distance education in the former Federal Republic of Germany (West Germany) was ushered in by the educational radio broadcasts around the end of the 1960s. Aside from the formation of the FernUniversität (Open University) in West Germany in 1975, there were significant developments in distance education occurring at the major universities in the German Democratic Republic (East Germany). After German reunification in 1990, the new unitary state launched programs to advance the development of distance education programs at conventional universities. Germany’s campus-based universities (Präsenzuniversitäten) created various entities, including central units and consortia of universities to design and market distance education programs. Hybridisation provides the necessary prerequisites for dual mode delivery, such as basic and continuing education programs, as well as for the combination of distance and campus-based education (Präsenzstudium). Hybridisation also has also opened the door for the creation of new programs. Following an initial phase in which distance education research is expected to centralize a trend towards decentralisation is likely to follow. The German Association for Distance Education (AG-F) offers a viable research network in distance education. Two dual mode case studies are also be surveyed: The Master of Arts degree, offered by the University of Koblenz-Landau, with Library Science as the second major, and the University of Kaiserslautern, where basic education will continue to be captured within the domain of the Präsenzstudium or campus-based education. The area in which distance education is flourishing most is within the field of academic continuing education, where external experts and authors are broadening the horizon of the campus. Multimedia networks will comprise the third generation of distance education.
Nowrousian, Minou ; Stajich, Jason E. ; Chu, Meiling ; Engh, Ines ; Espagne, Eric ; Halliday, Karen ; Kamerewerd, Jens ; Kempken, Frank ; Knab, Birgit ; Kuo, Hsiao-Che ; Osiewacz, Heinz D. ; Pöggeler, Stefanie ; Read, Nick D. ; Seiler, Stephan ; Smith, Kristina M. ; Zickler, Denise ; Kück, Ulrich ; Freitag, Michael
Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30–90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in ~4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for comparative studies to address basic questions of fungal biology.
Bachmann, Malte ; Horn, Katharina ; Rudloff, Ina ; Goren, Itamar ; Holdener, Martin ; Christen, Urs ; Darsow, Nicole ; Hunfeld, Klaus-Peter ; Köhl, Ulrike ; Kind, Peter ; Pfeilschifter, Josef ; Kraiczy, Peter ; Mühl, Heiko
If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-gamma but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1beta as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection.
Nold-Petry, Claudia A. ; Lehrnbecher, Thomas ; Jarisch, Andrea ; Schwabe, Dirk ; Pfeilschifter, Josef ; Mühl, Heiko ; Nold, Marcel Friedrich
Background: Familial hemophagocytosis (FHL) is a rare disease associated with defects in proteins involved in CD8+ T-cell cytotoxicity. Hyperactivation of immune cells results in a perilous, Th1-driven cytokine storm. We set out to explore the regulation of cytokines in an FHL patient who was clinically stable on low-dose immunosuppressive therapy after bone marrow transplantation over a six-month period. During this period, chimerism analyses showed that the fraction of host cells was between 1 and 10%. Both parents of the patient as well as healthy volunteers were studied for comparison. Methods/Principal Findings: Using ELISA, quantitative real-time PCR, and clinical laboratory methods, we investigated constitutive and inducible cytokines, polymorphisms, and clinical parameters in whole blood and whole blood cultures. Although routine laboratory tests were within the normal range, the chemokines IP-10 and IL-8 as well as the cytokine IL-27p28 were increased up to 10-fold under constitutive and stimulated conditions compared to healthy controls. Moreover, high levels of IFNgamma and TNFalpha were produced upon stimulation. Unexpectedly, IFNgamma induction of IL-18 binding protein (IL-18BP) was markedly reduced (1.6-fold vs 5-fold in controls). The patient's mother featured intermediately increased cytokine levels, whereas levels in the father were similar to those in the controls. Conclusions/Significance: Since IL-18 plays a major role in perpetuating hemophagocytosis, the failure of IFNgamma to induce IL-18BP may constitute a fundamental pathogenetic mechanism. Furthermore, increased production of IL-8 and IL-27 appears to be associated with this disease. Such dysregulation of cytokines was also found in the heterozygous parents, providing a novel insight into genotype-phenotype correlation of FHL which may encourage future research of this rare disease.
We solved the crystal structure of a novel type of c-ring isolated from Bacillus pseudofirmus OF4 at 2.5 Å, revealing a cylinder with a tridecameric stoichiometry, a central pore, and an overall shape that is distinct from those reported thus far. Within the groove of two neighboring c-subunits, the conserved glutamate of the outer helix shares the proton with a bound water molecule which itself is coordinated by three other amino acids of outer helices. Although none of the inner helices contributes to ion binding and the glutamate has no other hydrogen bonding partner than the water oxygen, the site remains in a stable, ion-locked conformation that represents the functional state present at the c-ring/membrane interface during rotation. This structure reveals a new, third type of ion coordination in ATP synthases. It appears in the ion binding site of an alkaliphile in which it represents a finely tuned adaptation of the proton affinity during the reaction cycle. Formal Correction: This article has been formally corrected to address the following errors. 1. The images for Figures S2 and S3 were incorrectly switched. The image that appears as Figure S2 should be Figure S3, and the image that appears as Figure S3 should be Figure S2. The figure legends appear in the correct order. Please view the correct... (read formal correction) 2. The images for Figures S2 and S3 were incorrectly switched. The image that appears as Figure S2 should be Figure S3, and the image that appears as Figure S3 should be Figure S2. The figure legends appear in the correct order. Please view the correct... (read formal correction)
Fendel, Rolf ; Brandts, Christian Hubertus ; Rudat, Annika ; Kreidenweiss, Andrea ; Steur, Claudia ; Appelmann, Iris ; Ruehe, Bettina ; Schröder, Paul ; Berdel, Wolfgang E. ; Kremsner, Peter G. ; Mordmüller, Benjamin Gottlieb
Background: Falciparum Malaria, an infectious disease caused by the apicomplexan parasite Plasmodium falciparum, is among the leading causes of death and morbidity attributable to infectious diseases worldwide. In Gabon, Central Africa, one out of four inpatients have severe malarial anemia (SMA), a life-threatening complication if left untreated. Emerging drug resistant parasites might aggravate the situation. This case control study investigates biomarkers of enhanced hemolysis in hospitalized children with either SMA or mild malaria (MM). Methods and Findings: Ninety-one children were included, thereof 39 SMA patients. Strict inclusion criteria were chosen to exclude other causes of anemia. At diagnosis, erythrophagocytosis (a direct marker for extravascular hemolysis, EVH) was enhanced in SMA compared to MM patients (5.0 arbitrary units (AU) (interquartile range (IR): 2.2–9.6) vs. 2.1 AU (IR: 1.3–3.9), p<0.01). Furthermore, indirect markers for EVH, (i.e. serum neopterin levels, spleen size enlargement and monocyte pigment) were significantly increased in SMA patients. Markers for erythrocyte ageing, such as CD35 (complement receptor 1), CD55 (decay acceleration factor) and phosphatidylserine exposure (annexin-V-binding) were investigated by flow cytometry. In SMA patients, levels of CD35 and CD55 on the red blood cell surface were decreased and erythrocyte removal markers were increased when compared to MM or reconvalescent patients. Additionally, intravascular hemolysis (IVH) was quantified using several indirect markers (LDH, alpha-HBDH, haptoglobin and hemopexin), which all showed elevated IVH in SMA. The presence of both IVH and EVH predicted the need for blood transfusion during antimalarial treatment (odds ratio 61.5, 95% confidence interval (CI): 8.9–427). Interestingly, this subpopulation is characterized by a significantly lowered reticulocyte production index (RPI, p<0.05). Conclusions: Our results show the multifactorial pathophysiology of SMA, whereby EVH and IVH play a particularly important role. We propose a model where removal of infected and non-infected erythrocytes of all ages (including reticulocytes) by EVH and IVH is a main mechanism of SMA. Further studies are underway to investigate the mechanism and extent of reticulocyte removal to identify possible interventions to reduce the risk of SMA development.
Proteins can be acetylated at the alpha-amino group of the N-terminal amino acid (methionine or the penultimate amino acid after methionine removal) or at the epsilon-amino group of internal lysines. In eukaryotes the majority of proteins are N-terminally acetylated, while this is extremely rare in bacteria. A variety of studies about N-terminal acetylation in archaea have been reported recently, and it was revealed that a considerable fraction of proteins is N-terminally acetylated in haloarchaea and Sulfolobus, while this does not seem to apply for methanogenic archaea. Many eukaryotic proteins are modified by differential internal acetylation, which is important for a variety of processes. Until very recently, only two bacterial proteins were known to be acetylation targets, but now 125 acetylation sites are known for E. coli. Knowledge about internal acetylation in archaea is extremely limited; only two target proteins are known, only one of which--Alba--was used to study differential acetylation. However, indications accumulate that the degree of internal acetylation of archaeal proteins might be underestimated, and differential acetylation has been shown to be essential for the viability of haloarchaea. Focused proteomic approaches are needed to get an overview of the extent of internal protein acetylation in archaea.
In this paper we discuss experimental evidence related to the structure and origin of the bosonic spectral function alpha 2F (omega) in high-temperature superconducting (HTSC) cuprates at and near optimal doping. Global properties of alpha 2F (omega), such as number and positions of peaks, are extracted by combining optics, neutron scattering, ARPES and tunnelling measurements. These methods give evidence for strong electron-phonon interaction (EPI) with 1<lambda ep <~ 3.5 in cuprates near optimal doping. We clarify how these results are in favor of the modified Migdal-Eliashberg (ME) theory for HTSC cuprates near optimal doping. In Section 2 we discuss theoretical ingredients—such as strong EPI, strong correlations—which are necessary to explain the mechanism of d-wave pairing in optimally doped cuprates. These comprise the ME theory for EPI in strongly correlated systems which give rise to the forward scattering peak. The latter is supported by the long-range part of EPI due to the weakly screened Madelung interaction in the ionic-metallic structure of layered HTSC cuprates. In this approach EPI is responsible for the strength of pairing while the residual Coulomb interaction and spin fluctuations trigger the d-wave pairing.
Combadière, Behazine ; Vogt, Annika ; Mahé, Brice ; Costagliola, Dominique ; Hadam, Sabrina ; Bonduelle, Olivia ; Sterry, Wolfram ; Staszewski, Shlomo ; Schaefer, Hans ; van der Werf, Sylvie ; Katlama, Christine ; Autran, Brigitte ; Blume-Peytav, Ulrike
Background: Current conventional vaccination approaches do not induce potent CD8 T-cell responses for fighting mostly variable viral diseases such as influenza, avian influenza viruses or HIV. Following our recent study on vaccine penetration by targeting of vaccine to human hair follicular ducts surrounded by Langerhans cells, we tested in the first randomized Phase-Ia trial based on hair follicle penetration (namely transcutaneous route) the induction of virus-specific CD8 T cell responses. Methods and Findings: We chose the inactivated influenza vaccine – a conventional licensed tetanus/influenza (TETAGRIP®) vaccine – to compare the safety and immunogenicity of transcutaneous (TC) versus IM immunization in two randomized controlled, multi-center Phase I trials including 24 healthy-volunteers and 12 HIV-infected patients. Vaccination was performed by application of inactivated influenza vaccine according to a standard protocol allowing the opening of the hair duct for the TC route or needle-injection for the IM route. We demonstrated that the safety of the two routes was similar. We showed the superiority of TC application, but not the IM route, to induce a significant increase in influenza-specific CD8 cytokine-producing cells in healthy-volunteers and in HIV-infected patients. However, these routes did not differ significantly for the induction of influenza-specific CD4 responses, and neutralizing antibodies were induced only by the IM route. The CD8 cell response is thus the major immune response observed after TC vaccination. Conclusions: This Phase Ia clinical trial (Manon05) testing an anti-influenza vaccine demonstrated that vaccines designed for antibody induction by the IM route, generate vaccine-specific CD8 T cells when administered transcutaneously. These results underline the necessity of adapting vaccination strategies to control complex infectious diseases when CD8 cellular responses are crucial. Our work opens up a key area for the development of preventive and therapeutic vaccines for diseases in which CD8 cells play a crucial role.
Purpose. The aim of this prospective longitudinal clinical pilot study was the evaluation of the effect on the Oral Health Impact Profile (OHIP) and patient-centered results of the envelope technique for Connective Tissue Graft (CTG). Methods. Sixteen patients (11 females) 24 to 71 years of age (42.6±11.1) received CTG that had been harvested from the palate and grafted using the envelope technique. Prior to and 3 months after surgery, all patients were examined clinically, completed the OHIP-G49 questionnaire, and were asked to judge the results of surgery. Results. Mean baseline recession depth of 2.5±0.8 mm was reduced by 1.2±0.9 mm (P<.001). Root coverage amounted to 48±39%. In 5 of 16 defects complete root coverage was achieved. Pain at the donor site was more pronounced than at recipient site regarding prevalence (8/6; P=.007), intensity (2.1±2.3/1.1±1.9 [visual analogue scale]; P=.016), and duration (1.4±2.3/0.8±1.4 days; P=.042). Baseline OHIP (15.7±12.1) was decreased by 3.6±8.5 three months after surgery (P=.139). Thirteen patients (81%) would undergo CTG surgery for similar reasons again. Conclusions. Root coverage using CTG according to the envelope technique provided improvement of OHIP as early as 3 months after surgery. Over all, patients were reasonably satisfied with the surgical technique and its results.
Nineteen-channel EEGs were recorded from the scalp surface of 30 healthy subjects (16 males and 14 females, mean age: 34 years, SD: 11.7 years) at rest and under trains of intermittent photic stimulation (IPS) at rates of 5, 10 and 20 Hz. Digitalized data were submitted to spectral analysis with fast fourier transformation providing the basis for the computation of global field power (GFP). For quantification, GFP values in the frequency ranges of 5, 10 and 20 Hz at rest were divided by the corresponding data obtained under IPS. All subjects showed a photic driving effect at each rate of stimulation. GFP data were normally distributed, whereas ratios from photic driving effect data showed no uniform behavior due to high interindividual variability. Suppression of alpha-power after IPS with 10 Hz was observed in about 70% of the volunteers. In contrast, ratios of alpha-power were unequivocal in all subjects: IPS at 20 Hz always led to a suppression of alpha-power. Dividing alpha-GFP with 20-Hz IPS by alpha-GFP at rest (R = a-GFPIPS/a-GFPrest) thus resulted in ratios lower than 1. We conclude that ratios from GFP data with 20-Hz IPS may provide a suitable paradigm for further investigations. Key words: EEG, Brain mapping, Intermittent photic stimulation, IPS, Global field power ratios
In this proceeding the emergence of a composite, adjoint-scalar field as an average over (trivial holonomy) calorons and anti-calorons is reviewed. This composite field acts as a background field to the dynamics of perturbative gluons, to which it is coupled via an effective, gauge invariant Lagrangian valid for temperatures above the deconfinement phase transition. Moreover a Higgs mechanism is induced by the composite field: two gluons acquire a quasi-particle thermal mass. On the phenomenological side the composite field acts as a bag pressure which shows a linear dependence on the temperature. As a result the linear rise with temperature of the trace anomaly is obtained and is compared to recent lattice studies.
Background: Pathogenic bacteria infecting both animals as well as plants use various mechanisms to transport virulence factors across their cell membranes and channel these proteins into the infected host cell. The type III secretion system represents such a mechanism. Proteins transported via this pathway (‘‘effector proteins’’) have to be distinguished from all other proteins that are not exported from the bacterial cell. Although a special targeting signal at the N-terminal end of effector proteins has been proposed in literature its exact characteristics remain unknown. Methodology/Principal Findings: In this study, we demonstrate that the signals encoded in the sequences of type III secretion system effectors can be consistently recognized and predicted by machine learning techniques. Known protein effectors were compiled from the literature and sequence databases, and served as training data for artificial neural networks and support vector machine classifiers. Common sequence features were most pronounced in the first 30 amino acids of the effector sequences. Classification accuracy yielded a cross-validated Matthews correlation of 0.63 and allowed for genome-wide prediction of potential type III secretion system effectors in 705 proteobacterial genomes (12% predicted candidates protein), their chromosomes (11%) and plasmids (13%), as well as 213 Firmicute genomes (7%). Conclusions/Significance: We present a signal prediction method together with comprehensive survey of potential type III secretion system effectors extracted from 918 published bacterial genomes. Our study demonstrates that the analyzed signal features are common across a wide range of species, and provides a substantial basis for the identification of exported pathogenic proteins as targets for future therapeutic intervention. The prediction software is publicly accessible from our web server ( www.modlab.org ).
Bacterial autotransporters represent a diverse family of proteins that autonomously translocate across the inner membrane of Gram-negative bacteria via the Sec complex and across the outer bacterial membrane. They often possess exceptionally long N-terminal signal sequences. We analyzed 90 long signal sequences of bacterial autotransporters and members of the two-partner secretion pathway in silico and describe common domain organization found in 79 of these sequences. The domains are in agreement with previously published experimental data. Our algorithmic approach allows for the systematic identification of functionally different domains in long signal sequences. Keywords: bacterial autotransporter, sequence analysis, pattern, protein targeting, signal peptide, protein trafficking
We propose a theory characterizing information systems (IS) as language communities which use and develop domain-specific languages for communication. Our theory is anchored in Language Critique, a branch of philosophy of language. In developing our theory, we draw on Systems Theory and Cybernetics as a theoretical framework. "Organization" of a system is directly related to communication of its sub-systems. "Big systems" are self-organizing and the control of this ability is disseminated throughout the system itself. Therefore, the influence on changes of the system from its outside is limited. Operations intended to change an organization are restricted to indirect approaches. The creation of domain-specific languages by the system itself leads to advantageous communication costs compared to colloquial communication at the price of set-up costs for language communities. Furthermore, we demonstrate how our theoretical constructs help to describe and predict the behavior of IS. Finally, we discuss implications of our theory for further research and IS in general. Keywords: Language Critique, language communities, communication, self-organization, IS research
Lipid rafts are specialized plasma membrane micro-domains highly enriched in cholesterol, sphingolipids and glycosylphosphatidylinositol (GPI) anchored proteins. Lipid rafts are thought to be located in the exofacial leaflet of plasma membranes. Functionally, lipid rafts are involved in intracellular trafficking of proteins and lipids, secretory and endocytotic pathways, signal transduction, inflammation and in cell-surface proteolysis. There has been substantial interest in lipid rafts in brain, both with respect to normal functioning and with certain neurodegenerative diseases. Based on the impact of lipid rafts on multitude biochemical pathways, modulation of lipid rafts is used to study related disease pathways and probably offers a target for pharmacological intervention. Lipid rafts can be targeted by modulation of its main components, namely cholesterol and sphingolipids. Other approaches include the modulation of membrane dynamics and it has been reported that protein-lipid interactions can vary the occurrence and composition of these membrane micro-domains. The present review summarizes the possibilities to modulate lipid rafts with focus on neuronal cells. Keywords: Lipid raft, cholesterol, membrane fluidity, statin, cyclodextrine, docosahexaenoic acid.
Since the world today is so significantly shaped by media technologies, it has become crucial for organizations, institutions and political parties to embrace this phenomenon in order for them to be able to communicate their message and programmes effectively. If they fail to do so, they in effect fail to exist in the public consciousness. Mass media hugely influence how culture is created: intelligence, artistic talent and technological innovation become visible through the media. The Roman Catholic Church, the world’s largest religious organization has, for the longest time, on the one hand denied the influence of the media, while on the other hand calling it ‘the work of evil’. When the Church eventually came to acknowledge the media as a powerful force, it proceeded to use this power as a mouthpiece for its authorities. The Catholic Church is still not wholly at ease with the media. The question is whether the Catholic Church has sufficiently familiarized itself with how the media function, in order to utilise the media to communicate the Church’s message to a large public audience. Against the background of ecclesial documents this article investigates the attitude of the Catholic Church towards the media as it has developed over the past 50 years.
Senft, Christian ; Polacin, Margareth ; Priester, Maike ; Seifert, Volker ; Kögel, Donat ; Weissenberger, Jakob
Background: New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. Methods: We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Results: Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Conclusions: Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas.
Background: The faunal and floral relationship of northward-drifting India with its neighboring continents is of general biogeographic interest as an important driver of regional biodiversity. However, direct biogeographic connectivity of India and Southeast Asia during the Cenozoic remains largely unexplored. We investigate timing, direction and mechanisms of faunal exchange between India and Southeast Asia, based on a molecular phylogeny, molecular clock-derived time estimates and biogeographic reconstructions of the Asian freshwater crab family Gecarcinucidae. Results: Although the Gecarcinucidae are not an element of an ancient Gondwana fauna, their subfamily Gecarcinucinae, and probably also the Liotelphusinae, evolved on the Indian Subcontinent and subsequently dispersed to Southeast Asia. Estimated by a model testing approach, this dispersal event took place during the Middle Eocene, and thus before the final collision of India and the Tibet-part of Eurasia. Conclusions: We postulate that the India and Southeast Asia were close enough for exchange of freshwater organisms during the Middle Eocene, before the final Indian--Eurasian collision. Our data support geological models that assume the Indian plate having tracked along Southeast Asia during its move northwards.
Freund, Tobias ; Wensing, Michel ; Mahler, Cornelia ; Gensichen, Jochen ; Erler, Antje ; Beyer, Martin ; Gerlach, Ferdinand M. ; Szecsenyi, Joachim ; Peters-Klimm, Frank
Background: Complex care management is seen as an approach to face the challenges of an ageing society with increasing numbers of patients with complex care needs. The Medical Research Council in the United Kingdom has proposed a framework for the development and evaluation of complex interventions that will be used to develop and evaluate a primary care-based complex care management program for chronically ill patients at high risk for future hospitalization in Germany. Methods and design: We present a multi-method procedure to develop a complex care management program to implement interventions aimed at reducing potentially avoidable hospitalizations for primary care patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, or chronic heart failure and a high likelihood of hospitalization. The procedure will start with reflection about underlying precipitating factors of hospitalizations and how they may be targeted by the planned intervention (pre-clinical phase). An intervention model will then be developed (phase I) based on theory, literature, and exploratory studies (phase II). Exploratory studies are planned that entail the recruitment of 200 patients from 10 general practices. Eligible patients will be identified using two ways of 'case finding': software based predictive modelling and physicians' proposal of patients based on clinical experience. The resulting subpopulations will be compared regarding healthcare utilization, care needs and resources using insurance claims data, a patient survey, and chart review. Qualitative studies with healthcare professionals and patients will be undertaken to identify potential barriers and enablers for optimal performance of the complex care management program. Discussion: This multi-method procedure will support the development of a primary care-based care management program enabling the implementation of interventions that will potentially reduce avoidable hospitalizations.
Background: Prospective, observational studies that enroll large numbers of patients with few exclusion criteria may better reflect actual ongoing clinical experience than randomized clinical trials. Our purpose was to obtain efficacy and safety information from a cohort of subjects exposed to latanoprost/timolol fixed combination (FC) for [greater than or equal to]18 months using a prospective, observational design. Methods: In all, 577 office-based ophthalmologists in Germany switched 2339 patients with glaucoma or ocular hypertension to latanoprost/timolol FC for medical reasons. Follow-up visits were scheduled for every 6 months over 24 months; physicians followed usual care routines. Intraocular pressure (IOP), visual field status, optic nerve head findings, and adverse events were recorded. Efficacy parameters were evaluated for the per protocol (PP) population; the safety population included subjects receiving [greater than or equal to]1 drop of FC. Physicians rated efficacy, tolerability, and subject compliance at month 24. Results: Of the 2339 subjects switched to latanoprost/timolol FC (safety population), the primary reasons for switching were inadequate IOP reduction (78.2%) and desire to simplify treatment with once-daily dosing (29.4%; multiple reasons possible). In all, 1317 (56.3%) subjects completed the study, and 1028 (44.0%) were included in the PP population. Most discontinuations were due to loss to follow-up. Change in mean IOP from baseline to month 6 was -4.0 +/- 4.31 mmHg, a reduction that was maintained throughout (P<0.05 for change at all time points). By investigator assessments, optic disc parameters and visual field were stable over 24 months, and there was no relationship between IOP reduction over 24 months and development of a visual field defect. More than 90% of physicians rated latanoprost/timolol FC as "very good" or "good" for efficacy (PP population), tolerability, and compliance. The FC was safe and well tolerated. No change in iris color was reported by most subjects (83.1%) at month 24. Conclusions: Over 24 months, latanoprost/timolol FC effectively lowers IOP levels and is well tolerated in patients with glaucoma or ocular hypertension who change from their previous ocular hypotensive therapy for medical reasons. Investigator assessments found optic disc parameters and visual field to be stable throughout 24 months of follow-up.
Friedrich-Rust, Mireen ; Rosenberg, William ; Parkes, Julie ; Herrmann, Eva ; Zeuzem, Stefan ; Sarrazin, Christoph
Background: FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers. Methods: In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively. Results: Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC. The accuracy (AUROC) for the diagnosis of significant fibrosis (F[greater than or equal to]2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.). For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.). Conclusion: FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.
Wetzel, Gerald ; Oelhaf, Hermann ; Kirner, Oliver ; Ruhnke, Roland ; Friedl-Vallon, Felix ; Kleinert, Anne ; Maucher, Guido ; Fischer, Herbert ; Birk, Manfred ; Wagner, Georg ; Engel, Andreas
Active chlorine species play a dominant role in the catalytic destruction of stratospheric ozone in the polar vortices during the late winter and early spring seasons. Recently, the correct understanding of the ClO dimer cycle was challenged by the release of new laboratory absorption cross sections (Pope et al., 2007) yielding significant model underestimates of observed ClO and ozone loss (von Hobe et al., 2007). Under this aspect, nocturnal Arctic stratospheric limb emission measurements carried out by the balloon version of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS-B) from Kiruna (Sweden) on 11 January 2001 and 20/21 March 2003 have been reanalyzed with regard to the chlorine reservoir species ClONO2 and the active species, ClO and ClOOCl (Cl2O2). New laboratory measurements of IR absorption cross sections of ClOOCl for various temperatures and pressures allowed for the first time the retrieval of ClOOCl mixing ratios from remote sensing measurements. High values of active chlorine (ClOx) of roughly 2.3 ppbv at 20 km were observed by MIPAS-B in the cold mid-winter Arctic vortex on 11 January 2001. While nighttime ClOOCl shows enhanced values of nearly 1.1 ppbv at 20 km, ClONO2 mixing ratios are less than 0.1 ppbv at this altitude. In contrast, high ClONO2 mixing ratios of nearly 2.4 ppbv at 20 km have been observed in the late winter Arctic vortex on 20 March 2003. No significant ClOx amounts are detectable on this date since most of the active chlorine has already recovered to its main reservoir species ClONO2. The observed values of ClOx and ClONO2 are in line with the established polar chlorine chemistry. The thermal equilibrium constants between the dimer formation and its dissociation, as derived from the balloon measurements, are on the lower side of reported data and in good agreement with values recommended by von Hobe et al. (2007). Calculations with the ECHAM/MESSy Atmospheric Chemistry model (EMAC) using established kinetics show similar chlorine activation and deactivation, compared to the measurements in January 2001 and March 2003, respectively.
Atmospheric observation-based global SF6 emissions - comparison of top-down and bottom-up estimates
(2009)
Levin, Ingeborg ; Naegler, Tobias ; Heinz, Renate ; Osusko, Daniel ; Cuevas, Emilio ; Engel, Andreas ; Ilmberger, Johann ; Langenfelds, Ray L. ; Neininger, Bruno ; Rohden, Christoph von ; Steele, L. Paul ; Weller, Rolf ; Worthy, Douglas E. ; Zimov, Sergej A.
Emissions of sulphur hexafluoride (SF6), one of the strongest greenhouse gases on a per molecule basis, are targeted to be collectively reduced under the Kyoto Protocol. Because of its long atmospheric lifetime (≈3000 years), the accumulation of SF6 in the atmosphere is a direct measure of its global emissions. Examination of our extended data set of globally distributed high-precision SF6 observations shows an increase in SF6 abundance from near zero in the 1970s to a global mean of 6.7 ppt by the end of 2008. In-depth evaluation of our long-term data records shows that the global source of SF6 decreased after 1995, most likely due to SF6 emission reductions in industrialised countries, but increased again after 1998. By subtracting those emissions reported by Annex I countries to the United Nations Framework Convention of Climatic Change (UNFCCC) from our observation-inferred SF6 source leaves a surprisingly large gap of more than 70–80% of non-reported SF6 emissions in the last decade.
Levin, Ingeborg ; Naegler, Tobias ; Heinz, Renate ; Osusko, Daniel ; Cuevas, Emilio ; Engel, Andreas ; Ilmberger, Johann ; Langenfelds, Ray L. ; Neininger, Bruno ; Rohden, Christoph von ; Steele, L. Paul ; Weller, Rolf ; Worthy, Douglas E. ; Zimov, Sergej A.
Emissions of sulphur hexafluoride (SF6), one of the strongest greenhouse gases on a per molecule basis, are targeted to be collectively reduced under the Kyoto Protocol. Because of its long atmospheric lifetime (estimated as 800 to 3200 years), the accumulation of SF6 in the atmosphere is a direct measure of its global emissions. Examination of our extended data set of globally distributed high-precision SF6 observations shows an increase in SF6 abundance from near zero in the 1970s to a global mean of 6.7 ppt by the end of 2008. In-depth evaluation of our long-term data records shows that the global source of SF6 decreased after 1995, most likely due to SF6 emission reductions in industrialised countries, but increased again after 1998. By subtracting those emissions reported by Annex I countries to the United Nations Framework Convention of Climatic Change (UNFCCC) from our observation-inferred SF6 source leaves a surprisingly large gap of more than 70–80% of non-reported SF6 emissions in the last decade. This suggests a strong under-estimation of emissions in Annex I countries and underlines the urgent need for independent atmospheric verification of greenhouse gases emissions accounting.
Wägele, Heike ; Deusch, Oliver ; Händeler, Katharina ; Martin, Rainer ; Schmitt, Valerie ; Christa, Gregor ; Pinzger, Britta ; Gould, Sven B. ; Dagan, Tal ; Klussmann-Kolb, Annette ; Martin, William
Sacoglossan sea slugs are unique in the animal kingdom in that they sequester and maintain active plastids that they acquire from the siphonaceous algae upon which they feed, making the animals photosynthetic. While most sacoglossan species digest their freshly ingested plastids within hours, four species from the family Plakobranchidae retain their stolen plastids (kleptoplasts) in a photosynthetically active state on time scales of weeks to months. The molecular basis of plastid maintenance within the cytosol of digestive gland cells in these photosynthetic metazoans is yet unknown, but is widely thought to involve gene transfer from the algal food source to the slugs based upon previous investigations of single genes. Indeed, normal plastid development requires hundreds of nuclear-encoded proteins, with protein turnover in photosystem II in particular known to be rapid under various conditions. Moreover, only algal plastids, not the algal nuclei, are sequestered by the animals during feeding. If algal nuclear genes are transferred to the animal either during feeding or in the germ line, and if they are expressed, then they should be readily detectable with deep-sequencing methods. We have sequenced expressed mRNAs from actively photosynthesizing, starved individuals of two photosynthetic sea slug species, Plakobranchus ocellatus Van Hasselt, 1824 and Elysia timida Risso, 1818. We find that nuclear-encoded, algal-derived genes specific to photosynthetic function are expressed neither in P. ocellatus nor in E. timida. Despite their dramatic plastid longevity, these photosynthetic sacoglossan slugs do not express genes acquired from algal nuclei in order to maintain plastid function.
New conditions of solvability based on a general theorem on the calculation of the index at infinity for vector fields that have degenerate principal linear part as well as degenerate ... next order ... terms are obtained for the 2 Pi-periodic problem for the scalar equation x'' +n2x=g(|x|)+f(t,x)+b(t) with bounded g(u) and f(t,x) -> 0 as |x| -> 0. The result is also applied to the solvability of a two-point boundary value problem and to resonant problems for equations arising in control theory.
AMS subject classifications: 47Hll, 47H30.
Methanogenic archaea are a group of strictly anaerobic microorganisms characterized by their strict dependence on the process of methanogenesis for energy conservation. Among the archaea, they are also the only known group synthesizing proteins containing selenocysteine or pyrrolysine. All but one of the known archaeal pyrrolysine-containing and all but two of the confirmed archaeal selenocysteine-containing protein are involved in methanogenesis. Synthesis of these proteins proceeds through suppression of translational stop codons but otherwise the two systems are fundamentally different. This paper highlights these differences and summarizes the recent developments in selenocysteine- and pyrrolysine-related research on archaea and aims to put this knowledge into the context of their unique energy metabolism.
A new artificial regulatory system for essential genes in yeast is described. It prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers introduced into their 5'UTRs. Exploiting direct RNA–ligand interaction renders auxiliary protein factors unnecessary. Therefore, our approach is strain independent and not susceptible to interferences by heterologous expressed regulatory proteins. We use a simple PCR-based strategy, which allows easy tagging of any target gene and the level of gene expression can be adjusted due to various tc aptamer-regulated promoters. As proof of concept, five differently expressed genes were targeted, two of which could not be regulated previously. In all cases, adding tc completely prevented growth and, as shown for Nop14p, rapidly abolished de novo protein synthesis providing a powerful tool for conditional regulation of yeast gene expression.
Falkenberg, Gerald ; Fleissner, Gerta ; Schuchardt, Kirsten ; Kühbacher, Markus ; Thalau, Peter ; Mouritsen, Henrik ; Heyers, Dominik ; Wellenreuther, Gerd ; Fleissner, Günther
The magnetic field sensors enabling birds to extract orientational information from the Earth’s magnetic field have remained enigmatic. Our previously published results from homing pigeons have made us suggest that the iron containing sensory dendrites in the inner dermal lining of the upper beak are a candidate structure for such an avian magnetometer system. Here we show that similar structures occur in two species of migratory birds (garden warbler, Sylvia borin and European robin, Erithacus rubecula) and a non-migratory bird, the domestic chicken (Gallus gallus). In all these bird species, histological data have revealed dendrites of similar shape and size, all containing iron minerals within distinct subcellular compartments of nervous terminals of the median branch of the Nervus ophthalmicus. We also used microscopic X-ray absorption spectroscopy analyses to identify the involved iron minerals to be almost completely Fe III-oxides. Magnetite (Fe II/III) may also occur in these structures, but not as a major Fe constituent. Our data suggest that this complex dendritic system in the beak is a common feature of birds, and that it may form an essential sensory basis for the evolution of at least certain types of magnetic field guided behavior.
Wisniewska, Joanna Marta ; Jäger, Natalie ; Freier, Anja ; Losch, Florian O. ; Wiesmüller, Karl-Heinz ; Walden, Peter ; Wrede, Paul ; Schneider, Gisbert ; Hiß, Jan Alexander
Experimental results are presented for 180 in silico designed octapeptide sequences and their stabilizing effects on the major histocompatibility class I molecule H-2Kb. Peptide sequence design was accomplished by a combination of an ant colony optimization algorithm with artificial neural network classifiers. Experimental tests yielded nine H-2Kb stabilizing and 171 nonstabilizing peptides. 28 among the nonstabilizing octapeptides contain canonical motif residues known to be favorable for MHC I stabilization. For characterization of the area covered by stabilizing and non-stabilizing octapeptides in sequence space, we visualized the distribution of 100,603 octapeptides using a self-organizing map. The experimental results present evidence that the canonical sequence motives of the SYFPEITHI database on their own are insufficient for predicting MHC I protein stabilization.
Linear-implicit versions of strong Taylor numerical schemes for finite dimensional Itô stochastic differential equations (SDEs) are shown to have the same order as the original scheme. The combined truncation and global discretization error of an gamma strong linear-implicit Taylor scheme with time-step delta applied to the N dimensional Itô-Galerkin SDE for a class of parabolic stochastic partial differential equation (SPDE) with a strongly monotone linear operator with eigenvalues lambda 1 <= lambda 2 <= ... in its drift term is then estimated by K(lambda N -½ + 1 + delta gamma) where the constant K depends on the initial value, bounds on the other coefficients in the SPDE and the length of the time interval under consideration.
AMS subject classifications: 35R60, 60H15, 65M15, 65U05.
Alternative education or teaching radicalism? New literature on Islamic education in Southeast Asia
(2009)
This review article focuses on three recent publications on Islamic education in Southeast Asia. While two are monographs on South Thailand and Myanmar/ Burma, one is a collection of essays on Indonesia, Malaysia, South Thailand, Cambodia, and the Southern Philippines. All works highlight local, regional and international educational networks, as well as their connections to the Indian subcontinent and the Middle East. Based chiefly on first-hand fieldwork, the works deliver an up-to-date and detailed picture of current discussions and developments regarding Islamic education in Southeast Asia. Key words Education ; Islam ; Southeast Asia ; Indonesia ; Malaysia ; Thailand ; Myanmar
Samples of freshly fallen snow were collected at the high alpine research station Jungfraujoch, Switzerland, during the Cloud and Aerosol Characterization Experiments (CLACE) 5 in February and March 2006. Sampling was carried out on the Sphinx platform. Headspace-solid-phase-dynamic extraction (HS-SPDE) combined with gas chromatography/mass spectrometry (GC/MS) was used to quantify C6–C10 n-aldehydes in the snow samples. The most abundant n-aldehyde was n-hexanal (median concentration 1.324 micro g L -1) followed by n-nonanal, n-decanal, n-octanal and n-heptanal (median concentrations 1.239, 0.863, 0.460, and 0.304 micro g L -1, respectively). A wide range of concentrations was found among individual snow samples, even for samples taken at the same time. Higher median concentrations of all n-aldehydes were observed when air masses reached Jungfraujoch from the north-northwest in comparison to air masses arriving from the southeast-southwest. Results suggest that the n-aldehydes detected most likely are of direct and indirect biogenic origin, and that they entered the snow through the particle phase.
Fries, Elke ; Haunold, Werner ; Starokozhev, Elena ; Palitzsch, Katrin ; Sitals, Robert ; Jaeschke, Wolfgang ; Püttmann, Wilhelm
Both, gas and particle scavenging contribute to the transport of organic compounds by ice crystals in the troposphere. To simulate these processes an experimental setup was developed to form airborne ice crystals under atmospheric conditions. Experiments were performed in a wall independent reactor (WIR) installed in a walk-in cold chamber maintained constantly at -20°C. Aerosol particles were added to the carrier gas of ambient air by an aerosol generator to allow heterogeneous ice formation. Temperature variations and hydrodynamic conditions of the WIR were investigated to determine the conditions for ice crystal formation and crystal growth by vapour deposition. In detail, the dependence of temperature variations from flow rate and temperature of the physical wall as well as temperature variations with an increasing reactor depth were studied. The conditions to provide a stable aerosol concentration in the carrier gas flow were also studied. The temperature distribution inside the reactor was strongly dependent on flow rate and physical wall temperature. At an inlet temperature of -20°C, a flow rate of 30 L•min exp -1 and a physical wall temperature of +5°C turned out to provide ideal conditions for ice formation. At these conditions a sharp and stable laminar down draft "jet stream" of cold air in the centre of the reactor was produced. Temperatures measured at the chamber outlet were kept well below the freezing point in the whole reactor depth of 1.0 m. Thus, melting did not affect ice formation and crystal growth. The maximum residence time for airborne ice crystals was calculated to at 40 s. Ice crystal growth rates increased also with increasing reactor depth. The maximum ice crystal growth rate was calculated at 2.82 mg• exp -1. Further, the removal efficiency of the cleaning device for aerosol particles was 99.8% after 10 min. A reliable particle supply was attained after a preliminary lead time of 15 min. Thus, the minimum lead time was determined at 25 min. Several test runs revealed that the WIR is suitable to perform experiments with airborne ice crystals.
Der Mediziner Prof. Charles Dinarello, 66, von der University of Colorado erhielt den mit 100 000 Euro dotierten Paul Ehrlich- und Ludwig Darmstaedter-Preis 2010. Der mit 60 000 Euro dotierte Paul Ehrlich-Nachwuchspreis ging an die Frankfurter Biologin Prof. Amparo Acker-Palmer, 41, vom Exzellenzcluster »Makromolekulare Komplexe« Frankfurt.
Blut-Untersuchungen ziehen sich wie ein roter Faden durch die verschiedenen Abteilungen des Frankfurter Instituts für Rechtsmedizin. Ob mit dem Skalpell, durch scharfsinnige Beobachtung oder Hightech-Laboranalytik: Spezialisierte Rechtsmediziner können einen Tathergang anhand von Blutspurenverteilungsmustern rekonstruieren, Toxikologen messen im Blut betäubende oder giftige Substanzen, Molekularbiologen ordnen Blutspuren über DNA-Profi le Personen zu und versuchen, mit molekulardiagnostischen Methoden unklare Todesursachen aufzuklären. Zwei konstruierte Todesfälle gewähren einen forensischen Blick auf das Blut.
Mit Blut unterzeichnete Dr. Faust seinen zweifelhaften Pakt mit dem Teufel. In der Kulturgeschichte des Menschen hat Blut von jeher eine mystisch aufgeladene Rolle gehabt, die sich in religiösen Ritualen, Heilpraktiken, Liebes- und Freundschaftsbünden niederschlug. Roland Prinzinger beginnt mit einigen Schlaglichtern auf die vielfältigen Bedeutungen des Blutes, die heute noch mitschwingen, wenn wir uns dem Thema nähern. Als Biologe erklärt er dann am Beispiel der Diagnostik bei Vögeln, warum Blut auch aus naturwissenschaftlicher Sicht ein »ganz besonderer Saft« ist.
Hundert Jahre nach seiner Premiere im Oktober 1910 findet der Kongress der Deutschen Gesellschaft für Soziologie wieder in Frankfurt am Main statt. Damit unterstreicht die Fachgesellschaft die Bedeutung, die dem Wissenschaftsstandort Frankfurt für die zeitgenössischen Sozialwissenschaften zukommt. Neben dem 1971 gegründeten Frankfurter Fachbereich Gesellschaftswissenschaften haben das traditionsreiche Institut für Sozialforschung, das Sigmund-Freud-Institut, das Cornelia-Goethe-Centrum sowie der Exzellenzcluster »Die Herausbildung normativer Ordnungen« das gegenwärtige Erscheinungsbild der Frankfurter Soziologie nachhaltig geprägt. ...
In welcher Welt leben wir? : Soziologiekongress zum Thema "Transnationale Vergesellschaftungen"
(2010)
Frankfurt wird vom 11. bis 15. Oktober zum fünften Mal Austragungsort des Kongresses der Deutschen Gesellschaft für Soziologie (DGS) sein. Zu diesem mittlerweile 35. DGS-Kongress – der erste fand vor 100 Jahren ebenfalls in Frankfurt statt – werden rund 3000 Wissenschaftlerinnen und Wissenschaftler aus aller Welt erwartet. ...
Das Bild unter der Schneedecke : visuelle Soziologie: Erforschung des Sozialen mit anderen Mitteln
(2010)
"Unter der Fotografie eines Menschen ist seine Geschichte wie unter einer Schneedecke vergraben", schrieb Siegfried Kracauer 1927 in seinem Essay "Das Ornament der Masse". Visuelle Soziologie nennt sich heute eine relativ junge Fachrichtung, die versucht, diese Schneedecke mit soziologischen Methoden beiseite zu räumen. Dann wird der Hintergrund sichtbar, auf dem die Geschichte des Bildes sich abspielt, das soziale Beziehungsgeflecht, dem die Fotografie ihre Existenz verdankt. Ist doch dieses Bild die Manifestation verschiedener Beziehungen, die sich etwa zwischen Fotograf und Fotografiertem, zwischen Betrachter und Betrachtetem, zwischen Auftraggeber und Nutzer entwickeln und in die ideologische Weltsichten ebenso eingehen wie die sozialen Lagen der Akteure. Visuelle Soziologie fragt also nach der Produktion, Distribution und Konsumtion von Bildern und stellt sie in Beziehung zur Sozialstruktur der Gesellschaft. ...
Welche Rolle spielt Religion – abseits von radikalem Extremismus – im politischen Geschehen der modernen westlichen Gesellschaften? Diese Frage motivierte unser Forschungsprojekt; wir untersuchen dabei einen ganz spezifischen Sachverhalt: Welchen Einfluss hat Religion darauf, ob Bürger staatliche Umverteilungspolitik unterstützen? ...
Argentinien gedenkt 2010 der zweihundertjährigen Unabhängigkeit, und es ist nach Mexiko 1992 und Brasilien 1994 das dritte lateinamerikanische Gastland der Frankfurter Buchmesse. Auf beiden Seiten des Atlantiks steigen die Zahlen der Buchpublikationen und der Übersetzungen. Grund genug, um im jährlich wiederkehrenden Termingeschäft des Markts Ausschau zu halten nach der die Jubelfeiern und Bestsellerlisten überdauernden Literatur. Auch in einer Phase der beschleunigten globalen Kommerzialisierung existiert sie noch.
Brustkrebs ist die häufigste Krebserkrankung und Todesursache bei Frauen. Die Forschung der letzten Jahrzehnte hat gezeigt, dass es sich dabei nicht um eine einzelne, immer gleich verlaufende Erkrankung handelt. Vielmehr geht man heute davon aus, dass Brustkrebs eine heterogene Erkrankung mit verschiedenen Subtypen darstellt. Sie lassen sich klinisch und molekular deutlich von einander unterscheiden. Wichtiges Ziel der modernen Forschung und ihrer Methoden ist daher die Entwicklung einer individuellen Therapie für jede einzelne Patientin.
In vielen Familien der Mittelschicht sind mittlerweile beide Ehepartner berufstätig. Das männliche Alleinverdiener-Modell verschwindet zwar nicht, aber nimmt ab. Die Arbeit zu Hause ist trotzdem noch ungleich verteilt und überwiegend Frauensache geblieben – wenn auch häufig unter neuen Vorzeichen: Oft übernehmen Migrantinnen, insbesondere aus Osteuropa, einen Teil der Care-Arbeit. Welche Konsequenzen hat dies für deren Familien?
Um Dynamiken und Netzwerke in den untersuchten Clubszenen und urbanen Räumen Berlins wissenschaftlich erfassen zu können, bedarf es einer multidimensionalen Herangehensweise. Ethnografi sche Methoden sind dabei von größter Bedeutung: teilnehmende Beobachtung im Alltag sowie auf Veranstaltungen vor Ort, fokussierte Gespräche mit Szenegängern und reflektierende Berichte über die eigene Positionierung als Forscherin. Das gesammelte Datenmaterial ist vielfältig: detaillierte Feldnotizen nach jedem Club- oder Barbesuch, aber auch nach relevanten Gesprächen, sei es »face-to-face«, über E-Mail- oder Chatverkehr nehmen den größten Part ein. Bildmaterial wie Plakate, Flyer und selbst gemachte Fotos in Clubs ergänzen das Schriftmaterial auch visuell. Das Verfolgen stadt- und kulturpolitischer Entwicklungen, Beobachtungen sozioökonomischer Gegebenheiten in den jeweiligen Szenen und der Einfl uss urbaner Infrastruktur auf das Ausgehverhalten sind weitere Mosaiksteine, die dazu beitragen, ein möglichst ganzheitliches Bild entstehen zu lassen. Nach der Feldforschungs- und Datenerhebungsphase wird das gesamte Datenmaterial ab Januar 2011 einer qualitativen Analyse unterzogen.
Migranten werden in politischen Debatten oft als festgefügte Gemeinschaft betrachtet, die in ihrer eigenen nach außen abgeschotteten Welt leben – in einer Parallelgesellschaft. Doch ist das wirklich so? Wie gestalten insbesondere junge Leute mit Migrationshintergrund ihre sozialen Bindungen, wenn sie sich in der urbanen Clubszene europäischer Großstädte bewegen? Das Team um die Soziologin und Kulturanthropologin Kira Kosnick untersucht die Dynamiken dieser Prozesse.
Blut steht für Leben - und für den Tod. Das ist in der Medizin nicht anders als in der Mythologie. Vor wenigen Jahrzehnten war die Diagnose Blutkrebs noch ein sicheres Todesurteil. Heute werden viele Leukämiekranke geheilt. An der Goethe-Universität setzt ein Schwerpunkt für Lymphom- und Leukämieforschung deutschlandweit Akzente bei Forschung und Diagnostik.
Wer sind unsere Leser? Was gefällt ihnen an »Forschung Frankfurt«? Welche Themen interessieren sie? Wie verständlich finden sie die Beiträge? Dies sind Fragen, auf die unsere Leserumfrage aus Heft 3/2009 aufschlussreiche Antworten ergeben hat. Die treuesten Leser sind Mitglieder der Freunde und Förderer der Goethe-Universität (29 Prozent), ein Fünftel sind Alumni, 18 Prozent Professoren.
Heparine sind die am häufigsten verwendeten Medikamente zur Kontrolle der Blutgerinnung. In hoher Dosierung werden sie in der Herzchirurgie eingesetzt, um Blutgerinnseln während einer Operation vorzubeugen. Ein am Institut für Biophysik entwickeltes Messverfahren erlaubt eine direkte und schnelle Messung des Heparinspiegels während des Eingriffs.
Wissenschaftler vom Exzellenzcluster »Makromolekulare Komplexe« der Goethe-Universität haben in Zusammenarbeit mit der Universität Freiburg die Architektur des größten Proteinkomplexes der zellulären Atmungskette aufgeklärt. Sie entdeckten einen bisher unbekannten Mechanismus der nergieumwandlung in diesem molekularen Komplex. Der Mechanismus ist notwendig, damit die Zelle die in der Nahrung gespeicherte Energie nutzen kann.
Ein Mikrokosmos sozialer Kontraste : mit soziologischem Blick durch das Frankfurter Bahnhofsviertel
(2010)
Das Frankfurter Bahnhofsviertel genießt einen überregionalen Ruf. Es ist sowohl als Vergnügungsmeile und Rotlichtbezirk, als auch wegen der öffentlichen Sichtbarkeit abweichenden Verhaltens bekannt – oder vielmehr berüchtigt. Bei Tag ist von dem pulsierenden Leben, das sich abends zwischen Hauptbahnhof und Schauspielhaus, zwischen Gründerzeit vil len und Bankhochhäusern abspielt, kaum etwas zu erahnen. Soziale Tatsachen wie die Unterbevölkerung des Stadtteils, die gezielte Ansiedlung von andernorts unerwünschten Branchen und Dienstleistungen, die Koexistenz verschiedener Kulturen stehen auf den ersten Blick erst recht außerhalb der Wahrnehmung. Dagegen fallen diejenigen Phänomene, die augenscheinlich den Bruch zwischen der »Normalität« und der Abweichung kennzeichnen, umso stärker ins Auge. Das gilt besonders für das Prostitutionsmilieu und die lokale Drogenszene.
Der Sport verlässt seine traditionellen Räume. Fest um- und begrenzte Territorien der Turnhalle, des Fußballplatzes oder des Leichtathletikstadions werden in vielen Trendsportarten ersetzt durch die Grenzenlosigkeit sowohl des Naturraums als auch des städtischen Raums. Jüngstes und vielleicht spektakulärstes Beispiel für die Urbanisierung des Sports ist eine aus Frankreich stammende Bewegungskunst mit dem Namen »Le Parkour«.
Drei Projekte der Goethe-Universität wurden in der dritten Ausschreibung der Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) zur Förderung bewilligt: Die LOEWE-Schwerpunkte »Neuronale Koordination« und »Digital Humanities« (Digitalisierung und Verfügbarmachung geisteswissenschaftlicher Forschungsinhalte) sowie die Gründung des LOEWE-Zentrums »Gen- und Zelltherapie«. Damit stehen den Wissenschaftlern der Goethe-Universität und ihren Kooperationspartnern in den kommenden drei Jahren 24,3 Millionen Euro für ihre Forschung zur Verfügung.
Die Autoren der Frankfurter Schule haben kilometerweise Gedrucktes hinterlassen, vieles davon ist inzwischen in Buchform erschienen und bestens dokumentiert. Aber Max Horkheimer, Theodor W. Adorno, Alexander Mitscherlich und die übrigen Mitstreiter nutzten auch die Chance, mit ihren Vorstellungen zur Philosophie und zur Gestaltung der jungen Demokratie in Deutschland im öffentlichen Diskurs präsent zu sein. Sie waren Meister des gesprochenen Wortes, oft im Radio vernehmbar, in Zeiten, als die lange Form im Hörfunk gepflegt wurde und noch keine belanglosen Talkshows die Medienwelt regierten. Adornos eigenwillige Diktion, allzu gern von den Adorniten in den 1970er und 1980er Jahren imitiert, Horkheimers schwäbischer Tonfall – all das lässt sich wiederfinden in den historischen Tondokumenten der Frankfurter Schule.
Wenn am 30. April 2011 der beschränkte Arbeitsmarkt für Personen aus den neuen EU-Beitrittsländern aufgehoben wird, wird dies auch neue Freiheiten für die etwa 100 000 illegal beschäftigten Haushaltshilfen aus Osteuropa bedeuten, die zurzeit alte Menschen in Deutschland betreuen. Vermutlich werden Privathaushalte als Arbeitsplatz deutlich unattraktiver gegenüber Tätigkeiten in der Gastronomie und im Einzelhandel. Frankreich bekommt diese Situation besser in den Griff, wie die ersten Ergebnisse eines EU-Projekts zeigen, das von Wissenschaftlern des Instituts für Wirtschaft, Arbeit und Kultur (IWAK) koordiniert wird.
Martin Möller, Professor für Algebra und Geometrie an der Goethe-Universität, erhält in der dritten Ausschreibungsrunde des European Research Council (ERC) einen »Starting Independent Researcher Grant«. Mit dem 2007 erstmals ausgeschriebenen Programm der ERC-Grants will die Europäische Union (EU) europaweit kreative Wissenschaftler und zukunftsweisende Projekte fördern. Für den Bereich »Physical Sciences and Engineering « waren 1205 Bewerbungen aus der ganzen Welt eingegangen, 2873 für die Ausschreibung insgesamt. Alleiniges Kriterium bei der Begutachtung der Anträge ist wissenschaftliche Exzellenz. Mit den vom ERC bewilligten Mitteln in Höhe von einer Million Euro für die nächsten fünf Jahre will Möller seine Forschergruppe um vier Mitarbeiter erweitern.
Drei Jahre lang hat die Deutsche Forschungsgemeinschaft die Erschließung und Digitalisierung des ethnografischen Bildarchivs und des Felsbildarchivs des Frobenius-Instituts an der Goethe-Universität mit über 500 000 Euro gefördert. Seit März ist das Ergebnis zu besichtigen. Die Bilddatenbank des Frobenius-Instituts ist online frei zugänglich unter der URL: http://bildarchiv.frobenius-katalog.de/
Immer auf den ersten Rängen : Leibniz-Preis für den Frankfurter Volkswirtschaftler Roman Inderst
(2010)
Wenn es um Superlative geht, dann steht der 40-jährige Prof. Roman Inderst immer ganz oben auf dem Treppchen: jung und schon auf den ersten Rängen unter den Top Ten der europäischen Wirtschaftswissenschaftler. Und am 15. März wurde er auch noch als jüngster unter den zehn Preisträgern mit dem wichtigsten deutschen Forschungspreis, dem mit 2,5 Millionen Euro dotierten Gottfried Wilhelm Leibniz-Preis 2010, ausgezeichnet.
Eisenhaltige kurze Nervenäste im Oberschnabel dienen offensichtlich ganz unterschiedlichen Vogelarten dazu, die Stärke des Erdmagnetfeldes zu messen und nicht nur seine Richtung wie ein Kompass zu bestimmen. Was die Frankfurter Neurobiologen Dr. Gerta Fleissner und ihr Mann Prof. Günther Fleissner bereits vor einigen Jahren bei Brieftauben entdeckten, können sie jetzt auch für andere Vogelarten belegen.
Plattformen für Social Communities im Internet, wie Facebook, StudiVZ und XING, haben in den vergangenen Jahren rasant an Popularität gewonnen. Auf ihnen versammeln sich bereits heute Millionen von Nutzern weltweit. Sie verbinden sich über virtuelle Freundeslisten und tauschen sich über gemeinsame Interessen und Aktivitäten aus. Immer häufger werden dazu auch mobile Endgeräte wie Handys verwendet, erlauben diese doch ständig in Kontakt mit der Community zu bleiben. Allerdings wollen viele Nutzer längst nicht jedem Mitglied einer Community alles preisgeben. Doch wie lässt sich die Privatsphäre in solchen Communities besser schützen? Dieser Frage geht das Forschungsprojekt PICOS nach.
Mit Kuppel und Minarett? Häufig wird die Frage nach der Form einer Moschee als Stellvertreterfrage nach der Akzeptanz des Islam wahrgenommen. Doch könnten offene Diskussionen über die Gestaltung neuer Moscheen auch einen Weg zur funktionierenden Zivilgesellschaft darstellen, ohne dass Muslime und Nichtmuslime ihr eigenes Profil aufgeben müssen.
Schlangengifte enthalten einen ganzen Arzneischrank voller hochwirksamer Stoffe, die binnen kurzer Zeit zu Schock, Lähmung oder unstillbaren Blutungen führen können. Forscher interessieren sich vor allem für Verbindungen, welche die Blutgerinnung hemmen, denn sie könnten pharmakologisch interessante Leitstrukturen für neue Wirkstoffe sein, die das Risiko eines Herzinfarkts, Gehirnschlags und anderer Thrombosen mindern.
Veldman, Alex ; Fischer, Doris ; Wong, Flora Y. ; Kreuz, Wolfhart ; Sasse, Michael ; Eberspächer, Bruno ; Mansmann, Ulrich ; Schosser, Rudolf
Introduction: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods: In Germany, patients receiving protein C concentrate (Ceprotin(R), Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this National, retrospective, multi-centered study. Results: Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions: This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.
Wurm, Jan Philip ; Meyer, Britta ; Bahr, Ute ; Held, Martin ; Frolow, Olga ; Kötter, Peter ; Engels, Joachim W. ; Heckel, Alexander ; Karas, Michael ; Entian, Karl-Dieter ; Wöhnert, Jens
Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen–Conradi syndrome—a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910–921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi in eukaryotic 18S rRNAs.