Universitätspublikationen
Refine
Year of publication
- 2021 (1819)
- 2020 (1464)
- 2019 (1192)
- 2018 (1060)
- 2022 (992)
- 2017 (897)
- 2016 (754)
- 2015 (606)
- 2014 (601)
- 2012 (590)
- 2013 (584)
- 2011 (444)
- 2010 (395)
- 2023 (393)
- 2024 (195)
- 2009 (180)
- 2008 (145)
- 2003 (111)
- 2007 (97)
- 2005 (88)
- 2004 (85)
- 2006 (81)
- 2002 (54)
- 2001 (38)
- 1999 (35)
- 1998 (34)
- 1969 (28)
- 2000 (27)
- 1976 (25)
- 1994 (25)
- 1987 (24)
- 1988 (24)
- 1966 (23)
- 1967 (23)
- 1996 (23)
- 1971 (22)
- 1997 (22)
- 1975 (21)
- 1968 (20)
- 1981 (20)
- 1995 (20)
- 1947 (18)
- 1962 (18)
- 1965 (18)
- 1970 (18)
- 1972 (18)
- 1974 (18)
- 1977 (18)
- 1991 (18)
- 1992 (18)
- 1993 (18)
- 1978 (17)
- 1913 (16)
- 1982 (16)
- 1989 (16)
- 1973 (15)
- 1990 (15)
- 1963 (14)
- 1964 (14)
- 1984 (14)
- 1960 (12)
- 1980 (12)
- 1985 (12)
- 1986 (11)
- 1983 (10)
- 1959 (9)
- 1950 (8)
- 1954 (8)
- 1957 (8)
- 1979 (8)
- 1953 (7)
- 1958 (7)
- 1952 (6)
- 1956 (6)
- 1961 (5)
- 1948 (4)
- 1951 (4)
- 1885 (3)
- 1897 (3)
- 1949 (3)
- 1910 (2)
- 1914 (2)
- 1939 (2)
- 1946 (2)
- 1955 (2)
- 1880 (1)
- 1881 (1)
- 1883 (1)
- 1896 (1)
- 1901 (1)
- 1903 (1)
- 1904 (1)
- 1906 (1)
- 1907 (1)
- 1908 (1)
- 1911 (1)
- 1916 (1)
- 1917 (1)
- 1918 (1)
- 1919 (1)
- 1921 (1)
- 1922 (1)
- 1923 (1)
- 1928 (1)
- 1929 (1)
- 1930 (1)
Document Type
- Article (13775) (remove)
Language
- English (11041)
- German (2282)
- Portuguese (222)
- Spanish (97)
- Italian (53)
- French (36)
- Multiple languages (9)
- Ukrainian (9)
- slo (7)
- Turkish (4)
Has Fulltext
- yes (13775)
Keywords
- inflammation (93)
- COVID-19 (84)
- SARS-CoV-2 (61)
- Adorno (56)
- cancer (43)
- apoptosis (42)
- crystal structure (41)
- Inflammation (39)
- aging (39)
- Ausstellung (38)
Institute
- Medizin (5131)
- Physik (1657)
- Biowissenschaften (1055)
- Biochemie und Chemie (990)
- Frankfurt Institute for Advanced Studies (FIAS) (737)
- Gesellschaftswissenschaften (726)
- Geowissenschaften (512)
- Präsidium (445)
- Philosophie (431)
- Informatik (397)
Dynamics of relativistic heavy-ion collisions is investigated on the basis of a simple (1+1)-dimensional hydrodynamical model in light-cone coordinates. The main emphasis is put on studying sensitivity of the dynamics and observables to the equation of state and initial conditions. Low sensitivity of pion rapidity spectra to the presence of the phase transition is demonstrated, and some inconsistencies of the equilibrium scenario are pointed out. Possible non-equilibrium effects are discussed, in particular, a possibility of an explosive disintegration of the deconfined phase into quark-gluon droplets. Simple estimates show that the characteristic droplet size should decrease with increasing the collective expansion rate. These droplets will hadronize individually by emitting hadrons from the surface. This scenario should reveal itself by strong non-statistical fluctuations of observables. Critical Point and Onset of Deconfinement 4th International Workshop July 9-13 2007 GSI Darmstadt,Germany
Event-by-event multiplicity fluctuations in nucleus-nucleus collisions from low SPS up to RHIC energies have been studied within the HSD transport approach. Fluctuations of baryonic number and electric charge also have been explored for Pb+Pb collisions at SPS energies in comparison to the experimental data from NA49. We find a dominant role of the fluctuations in the nucleon participant number for the final hadron multiplicity fluctuations and a strong influence of the experimental acceptance on the final results. Critical Point and Onset of Deconfinement - 4th International Workshop July 9 - 13, 2007 Darmstadt, Germany
Giftige Zwerge in der Umwelt? : Über Wirkungen von Nanomaterialien in aquatischen Ökosystemen
(2011)
In Deutschland hängen Bildungschancen wie in kaum einem anderen Land vom Bildungsstatus der Herkunftsfamilie ab. Vom Ideal einer Chancengleichheit sind wir weit entfernt. So verlässt beispielsweise jedes vierte Kind mit Migrationshintergrund die Schule ohne Abschluss. Viele Kinder aus sozial schwierigen Verhältnissen enden wie meist schon ihre Eltern in der Arbeitslosigkeit und in einem Leben am Rande der Gesellschaft.
Stammzellen aus dem Knochenmark werden seit Jahrzehnten gegen Blutkrebs eingesetzt. In der Zukunft sollen auch andere Krankheiten mit Stammzellen und therapeutischen Genen behandelt werden. Die an der Goethe-Universität geleisteten Vorarbeiten zeigen, dass der Standort wie kaum ein anderer geeignet ist, diese neuen und maßgeschneiderten Verfahren voran zubringen.
Während Bildungspolitiker heftig über die Abschaffung der Hauptschule streiten und Hamburger Bürger sich per Volksentscheid für den Erhalt des Gymnasiums ab Klasse 5 einsetzen, sind sich die meisten Bildungsforscher einig: Entscheidend ist nicht, wo, sondern wie Kinder unterrichtet und betreut werden. Wie kann es gelingen, pädagogische Interventionen den unterschiedlichen Lernvoraussetzungen so anzupassen, dass möglichst alle Schülerinnen und Schüler optimal gefördert werden? Um das herauszufi nden, bedarf es intensiver Anstrengungen in der Lehr-Lernforschung, wie sie in Frankfurt im Forschungszentrum IDeA unternommen werden.
Seit einigen Jahrzehnten wollen Biochemiker, Mediziner, Biologen und Pharmazeuten weltweit nicht mehr auf eine bioanalytische Methode verzichten, an deren Entwicklung der Frankfurter Wissenschaftler Prof. Dr. Michael Karas vom Institut für Pharmazeutische Chemie der Goethe-Universität maßgeblich beteiligt war. Die Rede ist von der Matrix-unterstützten Laser-Desorptions- / Ionisations-Massenspektrometrie – kurz MALDI-MS.
Sie sind nicht weniger intelligent als ihre gleichaltrigen Mitschüler, und doch sind ihre schulischen Leistungen meist schlechter: Kinder, die unter einer Störung mit Aufmerksamkeitsdefi zit und Hyperaktivität (ADHS) leiden, haben es schwer im Schulsystem. Wie können sie lernen, ihre Gefühle, Gedanken und Handlungen bewusst zu beeinfl ussen und sich nicht ständig ablenken zu lassen? Frankfurter Studien zeigen zum Beispiel, dass konkrete "Wenn-Dann-Pläne" ihre Konzentrationsfähigkeit deutlich verbessern können.
Yuniyanti Chuzaifah is one of the founders of "Voice of Concerned Mothers" (Suara Ibu Peduli or SIP) and later joined the "Coalition of Indonesian Women" (Koalisi Perempuan Indonesia or KPI). She studied at the Universities of Leiden and Amsterdam in the Netherlands, and later returned to Indonesia. Since March 2010 she has been the Director of the "Indonesian National Commission on Violence against Women" (Komnas Perempuan). This interview was conducted on 15 March 2010 at the organisation’s premises in Jakarta.
Wie entsteht Schmerz? Und wie kann man ihn lindern? Um diese Fragen beantworten zu können, untersuchen Forscher eine Gruppe von Schlüsselmolekülen, die Eicosanoide, und ihre Abbauprodukte. Dabei machen sie immer wieder überraschende Entdeckungen: Blockiert man etwa durch Schmerzmittel wie Acetylsalicylsäure gezielt die Entstehung des Abbauprodukts Prostaglandin, schützt dies auch vor Krebs. Verhindert man die Entstehung von Leukotrienen, lassen sich allergische Reaktionen wie Asthma, aber auch Krebs, Osteoporose und Herz-Kreislauf-Erkrankungen beeinflussen.
Introduction: Systemic inflammation (e.g. following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum. Methods: 338 patients admitted for elective cardiac surgery were included in this prospective observational clinical cohort study. Genomic DNA of patients was screened for TLR2 and TLR4 SNPs. Serum concentrations of ACTH, cortisol, interferon (IFN)-, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)- and granulocyte macro-phage-colony stimulating factor (GM-CSF) were determined before surgery, immediately post surgery and on the first postoperative day. Results: 13 patients were identified as TLR2 SNP carrier, 51 as TLR4 SNP carrier and 274 pa-tients as non-carrier. Basal levels of ACTH, cortisol and cytokines did not differ between groups. In all three groups a significant, transient perioperative rise of cortisol could be ob-served. However, only in the non-carrier group this was accompanied by a significant ACTH rise, TLR4 SNP carriers had significant lower ACTH levels compared to non-carriers ((mean[95% confidence intervals]) non-carriers: 201.9[187.7 to 216.1]pg/ml; TLR4 SNP car-riers: 149.9[118.4 to 181.5]pg/ml; TLR2 SNP carriers: 176.4[110.5 to 242.3]pg/ml). Compared to non-carriers, TLR4 SNP carriers showed significant lower serum IL-8, IL-10 and GM-CSF peaks ((mean[95% confidence intervals]): IL-8: non-carriers: 42.6[36.7 to 48.5]pg/ml, TLR4 SNP carriers: 23.7[10.7 to 36.8]pg/ml; IL-10: non-carriers: 83.8[70.3 to 97.4]pg/ml, TLR4 SNP carriers: 54.2[24.1 to 84.2]pg/ml; GM-CSF: non-carriers: 33.0[27.8 to 38.3]pg/ml, TLR4 SNP carriers: 20.2[8.6 to 31.8]pg/ml). No significant changes over time or between the groups were found for the other cytokines. Conclusions: Regulation of the immunoendocrine stress response during systemic inflamma-tion is influenced by the presence of a TLR4 SNP. Cardiac surgical patients carrying this ge-notype showed decreased serum concentrations of ACTH, IL-8, IL-10 and GM-CSF. This finding might have impact on interpreting previous and designing future trials on diagnosing and modulating immunoendocrine dysregulation (e.g. adrenal insufficiency) during systemic inflammation and sepsis.
Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae
(2011)
Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail.
PERIOD proteins are central components of the Drosophila and mammalian circadian clocks. The crystal structure of a Drosophila PERIOD (dPER) fragment comprising two PER-ARNT-SIM (PAS) domains (PAS-A and PAS-B) and two additional C-terminal alpha-helices (alphaE and alphaF) has revealed a homodimer mediated by intermolecular interactions of PAS-A with tryptophane 482 in PAS-B and helix alphaF. Here we present the crystal structure of a monomeric PAS domain fragment of dPER lacking the alphaF helix. Moreover, we have solved the crystal structure of a PAS domain fragment of the mouse PERIOD homologue mPER2. The mPER2 structure shows a different dimer interface than dPER, which is stabilized by interactions of the PAS-B beta-sheet surface including tryptophane 419 (equivalent to Trp482dPER). We have validated and quantitatively analysed the homodimer interactions of dPER and mPER2 by site-directed mutagenesis using analytical gel filtration, analytical ultracentrifugation, and co-immunoprecipitation experiments. Furthermore we show, by yeast-two-hybrid experiments, that the PAS-B beta-sheet surface of dPER mediates interactions with TIMELESS (dTIM). Our study reveals quantitative and qualitative differences between the homodimeric PAS domain interactions of dPER and its mammalian homologue mPER2. In addition, we identify the PAS-B beta-sheet surface as a versatile interaction site mediating mPER2 homodimerization in the mammalian system and dPER-dTIM heterodimer formation in the Drosophila system.
In the next years the Facility for Antiproton and Ion Research FAIR will be constructed at the GSI Helmholtzzentrum fur Schwerionenforschung in Darmstadt, Germany. This new accelerator complex will allow for unprecedented and pathbreaking research in hadronic, nuclear, and atomic physics as well as in applied sciences. This manuscript will discuss some of these research opportunities, with a focus on few-body physics.
The energy dependence of the local and violation in Au+Au and Cu+Cu collisions in a large energy range is estimated within a simple phenomenological model. It is expected that at LHC the chiral magnetic effect will be about 20 times weaker than at RHIC. At lower energy range, covered by the low-energy scan at RHIC and future NICA/FAIR facilities, the created magnetic field strength and energy density of deconfined matter are rather high providing necessary conditions for the chiral magnetic effect. However, the particular model for the chiral magnetic effect predicts that this effect should vanish sharply at energy somewhere above the top SPS one. To elucidate CME background effects the Hadron-String-Dynamics (HSD) transport model including electromagnetic fields is put forward. Importance of new planning experiments at LHC and for the low-energy RHIC scan program is emphasized.
Effects of nuclear orientation on fusion and fission in the reaction using 238U target nucleus
(2010)
Fission fragment mass distributions in the reaction of 30Si+238U were measured around the Coulomb barrier. At the above-barrier energies, the mass distribution showed a Gaussian shape. At the subbarrier energies, triple-humped distribution was observed, which consists of symmetric fission and asymmetric fission peaked at AL/AH ~ 90/178. The asymmetric fission should be attributed to quasifission from the results of the measured evaporation residue (ER) cross-sections for 30Si+238U. The cross-section for 263Sg at the abovebarrier energy agree with the statistical model calculation which assumes that the measured fission cross-section originates from fusion-fission, whereas the one for 264 Sg measured at the sub-barrier energy is smaller than the calculation, which suggests the presence of quasifission.
We examine the scaling trends in particle multiplicity and flow observables between SPS, RHIC and LHC, and discuss their compatibility with popular theoretical models. We examine the way scaling trends between SPS and RHIC are broken at LHC energies, and suggest experimental measurements which can further clarify the situation.
The mass-dependent structure of the composite nucleus is shown based on three-dimensional timedependent Hartree-Fock calculations with Skyrme interactions (SLy4d and SkM*). One remarkable result is that the isovector monopole excitation dominantly appears for collisions of heavy nuclei, and the isovector dipole excitation for those of light ones. Such a difference found in the dynamical structure of composite nucleus plays a role in the equilibration of charge.
We derive the equations of second order dissipative fluid dynamics from the relativistic Boltzmann equation following the method of W. Israel and J. M. Stewart [1]. We present a frame independent calculation of all first- and second-order terms and their coefficients using a linearised collision integral. Therefore, we restore all terms that were previously neglected in the original papers of W. Israel and J. M. Stewart.
We present results on Hanbury Brown-Twiss (HBT) radii extracted from the Ultra-relativistic Molecular Dynamics (UrQMD) approach to relativistic heavy ion collisions. The present investigation provides a comparison of results from pure hadronic transport calculations to a Boltzmann + Hydrodynamic hybrid approach with an intermediate hydrodynamic phase. For the hydrodynamic phase different Equations of State (EoS) have been employed, i.e. bag model, hadron resonance gas and a chiral EoS. The influence of various freeze-out scenarios has been investigated and shown to be negligible if hadronic rescatterings after the hydrodynamic evolution are included. Furthermore, first results of the source tilt from azimuthal sensitive HBT and the direct extraction from the transport model are presented and exhibit a very good agreement with E895 data at AGS.
A mechanism for locally density-dependent dynamic parton rearrangement and fusion has been implemented into the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) approach. The same mechanism has been previously built in the Quark Gluon String Model (QGSM). This rearrangement and fusion approach based on parton coalescence ideas enables the description of multi-particle interactions, namely 3 -> 3 and 3 -> 2, between (pre)hadronic states in addition to standard binary interactions. The UrQMD model (v2.3) extended by these additional processes allows to investigate implications of multi-particle interactions on the reaction dynamics of ultrarelativistic heavy ion collisions. The mechanism, its implementation and first results of this investigation are presented and discussed.
We present the current status of hybrid approaches to describe heavy ion collisions and their future challenges and perspectives. First we present a hybrid model combining a Boltzmann transport model of hadronic degrees of freedom in the initial and final state with an optional hydrodynamic evolution during the dense and hot phase. Second, we present a recent extension of the hydrodynamical model to include fluctuations near the phase transition by coupling a chiral field to the hydrodynamic evolution.
Fast thermalization and a strong build up of elliptic flow of QCD matter were investigated within the pQCD based 3+1 dimensional parton transport model BAMPS including bremsstrahlung 2 <-> 3 processes. Within the same framework quenching of gluonic jets in Au+Au collisions at RHIC can be understood. The development of conical structure by gluonic jets is investigated in a static box for the regimes of small and large dissipation. Furthermore we demonstrate two different approaches to extract the shear viscosity coefficient n from a microscopical picture.
We study the kinetic and chemical equilibration in 'infinite' parton-hadron matter within the Parton-Hadron-String Dynamics transport approach, which is based on a dynamical quasiparticle model for partons matched to reproduce lattice-QCD results – including the partonic equation of state – in thermodynamic equilibrium. The 'infinite' matter is simulated within a cubic box with periodic boundary conditions initialized at different baryon density (or chemical potential) and energy density. The transition from initially pure partonic matter to hadronic degrees of freedom (or vice versa) occurs dynamically by interactions. Different thermody-namical distributions of the strongly-interacting quark-gluon plasma (sQGP) are addressed and discussed.
Heavy quark and charmonium production as well as their space-time evolution are studied in transport simulations of heavy-ion collisions at RHIC and LHC. In the partonic transport model Boltzmann Approach of MultiParton Scatterings (BAMPS) heavy quarks can be produced in initial hard parton scatterings or during the evolution of the quark-gluon plasma. Subsequently, they interact with the medium via binary scatterings with a running coupling and a more precise Debye screening which is derived from hard thermal loop calculations, participate in the flow and lose energy. We present results of the elliptic flow and nuclear modification factor of heavy quarks and compare them to available data. Furthermore, preliminary results on J/psi suppression at forward and mid-rapidity are reported for central and non-central collisions at RHIC. For this, we study cold nuclear matter effects and the dissociation as well as regeneration of J/psi in the quark-gluon plasma. XLIX International Winter Meeting on Nuclear Physics 24-28 January 2011 BORMIO, Italy
The eukaryotic glyoxalase system consists of two enzymatic components, glyoxalase I (lactoylglutathionelyase) and glyoxalase II (hydroxyacylglutathione hydrolase). These enzymes are dedicated to the removal of toxic alpha-oxoaldehydes like methylglyoxal (MG). MG is formed as a by-product of glycolysis and MG toxicity results from its damaging capability leading to modifications of proteins, lipids and nucleic acids. An efficient removal of MG appears to be essential to ensure cellular functionality and viability. Here we study the effects of the genetic modulation of genes encoding the components of the glyoxalase system in the filamentous ascomycete and aging model Podospora anserina. Overexpression of PaGlo1 leads to a lifespan reduction on glucose rich medium, probably due to depletion of reduced glutathione. Deletion of PaGlo1 leads to hypersensitivity against MG added to the growth medium. A beneficial effect on lifespan is observed when both PaGlo1 and PaGlo2 are overexpressed and the corresponding strains are grown on media containing increased glucose concentrations. Notably, the double mutant has a ‘healthy’ phenotype without physiological impairments. Moreover, PaGlo1/PaGlo2_OEx strains are not long-lived on media containing standard glucose concentrations suggesting a tight correlation between the efficiency and capacity to remove MG within the cell, the level of available glucose and lifespan. Overall, our results identify the up-regulation of both components of the glyoxalase system as an effective intervention to increase lifespan in P. anserina. Key words: Podospora anserina, aging, lifespan, glycation, glucose, methylglyoxal, advanced glycation end products
TIM23-mediated insertion of transmembrane alpha-helices into the mitochondrial inner membrane
(2011)
While overall hydrophobicity is generally recognized as the main characteristic of transmembrane (TM) alpha-helices, the only membrane system for which there are detailed quantitative data on how different amino acids contribute to the overall efficiency of membrane insertion is the endoplasmic reticulum (ER) of eukaryotic cells. Here, we provide comparable data for TIM23-mediated membrane protein insertion into the inner mitochondrial membrane of yeast cells. We find that hydrophobicity and the location of polar and aromatic residues are strong determinants of membrane insertion. These results parallel what has been found previously for the ER. However, we see striking differences between the effects elicited by charged residues flanking the TM segments when comparing the mitochondrial inner membrane and the ER, pointing to an unanticipated difference between the two insertion systems. Keywords: CoxVa , membrane protein , Mgm1p , mitochondria , TIM23
G-quadruplex topologies of telomeric repeat sequences from vertebrates were investigated in the presence of molecular crowding (MC) mimetics, namely polyethylene glycol 200 (PEG), Ficoll 70 as well as Xenopus laevis egg extract by CD and NMR spectroscopy and native PAGE. Here, we show that the conformational behavior of the telomeric repeats in X. laevis egg extract or in Ficoll is notably different from that observed in the presence of PEG. While the behavior of the telomeric repeat in X. laevis egg extract or in Ficoll resembles results obtained under dilute conditions, PEG promotes the formation of high-order parallel topologies. Our data suggest that PEG should not be used as a MC mimetic.
Background: FTY720, an immunomodulator derived from a fungal metabolite which reduces circulating lymphocyte counts by increasing the homing of lymphocytes to the lymph nodes has recently gained interest in stroke research. The aim of this study was to evaluate the protective efficacy of FTY720 in cerebral ischemia in two different application paradigms and to gather first data on the effect of FTY720 on the rate of spontaneous bacterial infections in experimental stroke. Methods: Middle cerebral artery occlusion (MCAO) in C57BL/6 mice (strain J, groups of 10 animals) was performed with two different durations of ischemia (90 min and 3 h) and FTY720 was applied 2 h after vessel occlusion to study the impact of reperfusion on the protective potency of FTY720. Lesion size was determined by TTC staining. Mice treated with FTY720 or vehicle were sacrificed 48 h after 90 min MCAO to determine the bacterial burden in lung and blood. Results: FTY720 1 mg/kg significantly reduced ischemic lesion size when administered 2 h after the onset of MCAO for 3 h (45.4 +/- 22.7 mm3 vs. 84.7 +/- 23.6 mm3 in control mice, p = 0.001) and also when administered after reperfusion, 2 h after the onset of MCAO for 90 min (31.1 +/- 28.49 mm3 vs. 69.6 +/- 27.2 mm3 in control mice, p = 0.013). Bacterial burden of lung homogenates 48 h after stroke did not increase in the group treated with the immunomodulator FTY720 while there was no spontaneous bacteremia 48 h after MCAO in treated and untreated animals. Conclusions: Our results corroborate the experimental evidence of the protective effect of FTY720 seen in different rodent stroke models. Interestingly, we found no increase in bacterial lung infections even though FTY720 strongly reduces the number of circulating leukocytes.
Background: Studies on allele length polymorphism designate several glacial refugia for Norway spruce (Picea abies) in the South Carpathian Mountains, but infer only limited expansion from these refugia after the last glaciation. To better understand the genetic dynamics of a South Carpathian spruce lineage, we compared ancient DNA from 10,700 and 11,000-year-old spruce pollen and macrofossils retrieved from Holocene lake sediment in the Retezat Mountains with DNA extracted from extant material from the same site. We used eight primer pairs that amplified short and variable regions of the spruce cpDNA. In addition, from the same lake sediment we obtained a 15,000-years-long pollen accumulation rate (PAR) record for spruce that helped us to infer changes in population size at this site. Results: We obtained successful amplifications for Norway spruce from 17 out of 462 pollen grains tested, while the macrofossil material provided 22 DNA sequences. Two fossil sequences were found to be unique to the ancient material. Population genetic statistics showed higher genetic diversity in the ancient individuals compared to the extant ones. Similarly, statistically significant Ks and Kst values showed a considerable level of differentiation between extant and ancient populations at the same loci. Lateglacial and Holocene PAR values suggested that population size of the ancient population was small, in the range of 1/10 or 1/5 of the extant population. PAR analysis also detected two periods of rapid population growths (from ca. 11,100 and 3900 calibrated years before present (cal yr BP)) and three bottlenecks (around 9180, 7200 and 2200 cal yr BP), likely triggered by climatic change and human impact. Conclusion: Our results suggest that the paternal lineages observed today in the Retezat Mountains persisted at this site at least since the early Holocene. Combination of the results from the genetic and the PAR analyses furthermore suggests that the higher level of genetic variation found in the ancient populations and the loss of ancient allele types detected in the extant individuals were likely due to the repeated bottlenecks during the Holocene. This study demonstrates how past population size changes inferred from PAR records can be efficiently used in combination with ancient DNA studies. The joint application of palaeoecological and population genetic analyses proved to be a powerful tool to understand the influence of past population demographic changes on the haplotype diversity and genetic composition of forest tree species.
Anfang des 20. Jahrhunderts regierte Europa über ca. 85% des globalen Territoriums in Form von Kolonien, Protektoraten und Dependancen. Die koloniale Expansion war ein exorbitanter und gewalttätiger Prozess, der durch Ausbeutung, Versklavung und Diebstahl charakterisiert war. Es stellt sich deswegen die Frage, warum sich innerhalb der westlichen wissenschaftlichen Disziplinen lange Zeit nur eine kleine Minderheit diesem Ereignis analytisch angenommen hat. Keine große intellektuelle Anstrengung ist vonnöten, um zu verstehen, dass eine solch massive territoriale Expansion, die zum Teil über Jahrhunderte gewaltvoll erhalten wurde, erstens nicht nur durch militärische Präsenz möglich war, zweitens nicht mit der bloßen formalen Unabhängigkeit der kolonisierten Staaten zu einem Ende kommen konnte und schließlich kaum nur Spuren in den kolonisierten Ländern hinterlassen haben kann, sondern auch den globalen Norden prägten. Postkoloniale Studien nähern sich dieser Komplexität und irritieren dabei die Vorstellung einer zwangsläufigen, geradezu naturwüchsigen, kolonialen Beherrschung durch Europa. Sie werfen einen Blick auf die Mannigfaltigkeit kolonialer Interventionen und deren Wirkmächtigkeit bis in die heutigen Tage (etwa Randeria/Eckert 2009).
In ihrem Buch "Cultivating Humanity" formuliert Martha Nussbaum folgenden Appell: "(…) die Welt um uns herum ist unausweichlich international. Themen vom Handel bis zur Landwirtschaft – über die Menschenrechte bis hin zu der Linderung von Hungersnöten – fordern uns dazu heraus, den Blick über eng gefasste Gruppenloyalitäten hinaus zu wagen und weit entfernte Lebenswirklichkeiten zu berücksichtigen. (…) Die Kultivierung unserer Menschlichkeit in einer komplexen und ineinander verflochtenen Welt, bedarf eines Verständnisses über die Art und Weise in der gemeinsame Bedürfnisse und Ziele in unterschiedlichen Lebensverhältnissen je verschieden identifiziert und verfolgt werden" (1997, 10). Diese Forderung, die das liberale westliche Individuum dazu aufruft, sich angesichts zunehmender globaler Interdependenzen für Belange verantwortlich zu zeigen, die über das jeweilige Eigeninteresse hinausgehen, erscheint auf den ersten Blick als ein überaus lobenswertes Unternehmen.
Background: Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children. Methods: Forty four Caucasian children (ages 8-14) meeting diagnostic criteria of social phobia according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; APA, 1994) were randomly allocated to either a newly developed CBT program focusing on cognition according to the model of Clark and Wells (n = 21) or a wait-list control group (n = 23). The primary outcome measure was clinical improvement. Secondary outcomes included improvements in anxiety coping, dysfunctional cognitions, interaction frequency and comorbid symptoms. Outcome measures included child report and clinican completed measures as well as a diagnostic interview. Results: Significant differences between treatment participants (4 dropouts) and controls (2 dropouts) were observed at post test on the German version of the Social Phobia and Anxiety Inventory for Children. Furthermore, in the treatment group, significantly more children were free of diagnosis than in wait-list group at post-test. Additional child completed and clinician completed measures support the results. Discussion: The study is a first step towards investigating whether CBT focusing on cognition is efficacious in treating children with social phobia. Future research will need to compare this treatment to an active treatment group. There remain the questions of whether the effect of the treatment is specific to the disorder and whether the underlying theoretical model is adequate. Conclusion: Preliminary support is provided for the efficacy of the cognitive behavioral treatment focusing on cognition in socially phobic children. Active comparators should be established with other evidence-based CBT programs for anxiety disorders, which differ significantly in their dosage and type of cognitive interventions from those of the manual under evaluation (e.g. Coping Cat).
Background: The interferon-inducible immunity-related GTPases (IRG proteins/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite, Toxoplasma gondii, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane. Results: Irga6 forms GTP-dependent oligomers in vitro and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SRalpha). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for trans-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of T. gondii, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism. Conclusions: The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.
Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.
Background: The combination of high-throughput transcript profiling and next-generation sequencing technologies is a prerequisite for genome-wide comprehensive transcriptome analysis. Our recent innovation of deepSuperSAGE is based on an advanced SuperSAGE protocol and its combination with massively parallel pyrosequencing on Roche's 454 sequencing platform. As a demonstration of the power of this combination, we have chosen the salt stress transcriptomes of roots and nodules of the third most important legume crop chickpea (Cicer arietinum L.). While our report is more technology-oriented, it nevertheless addresses a major world-wide problem for crops generally: high salinity. Together with low temperatures and water stress, high salinity is responsible for crop losses of millions of tons of various legume (and other) crops. Continuously deteriorating environmental conditions will combine with salinity stress to further compromise crop yields. As a good example for such stress-exposed crop plants, we started to characterize salt stress responses of chickpeas on the transcriptome level. Results: We used deepSuperSAGE to detect early global transcriptome changes in salt-stressed chickpea. The salt stress responses of 86,919 transcripts representing 17,918 unique 26bp deepSuperSAGE tags (UniTags) from roots of the salt-tolerant variety INRAT-93 two hours after treatment with 25 mM NaCl were characterized. Additionally, the expression of 57,281 transcripts representing 13,115 UniTags was monitored in nodules of the same plants. From a total of 144,200 analyzed 26bp tags in roots and nodules together, 21,401 unique transcripts were identified. Of these, only 363 and 106 specific transcripts, respectively, were commonly up- or down-regulated (>3.0-fold) under salt stress in both organs, witnessing a differential organ-specific response to stress. Profiting from recent pioneer works on massive cDNA sequencing in chickpea, more than 9,400 UniTags were able to be linked to UniProt entries. Additionally, gene ontology (GO) categories over-representation analysis enabled to filter out enriched biological processes among the differentially expressed UniTags. Subsequently, the gathered information was further cross-checked with stress-related pathways. From several filtered pathways, here we focus exemplarily on transcripts associated with the generation and scavenging of reactive oxygen species (ROS), as well as on transcripts involved in Na+ homeostasis. Although both processes are already very well characterized in other plants, the information generated in the present work is of high value. Information on expression profiles and sequence similarity for several hundreds of transcripts of potential interest is now available. Conclusions: This report demonstrates, that the combination of the high-throughput transcriptome profiling technology SuperSAGE with one of the next-generation sequencing platforms allows deep insights into the first molecular reactions of a plant exposed to salinity. Cross validation with recent reports enriched the information about the salt stress dynamics of more than 9,000 chickpea ESTs, and enlarged their pool of alternative transcripts isoforms. As an example for the high resolution of the employed technology that we coin deepSuperSAGE, we demonstrate that ROS-scavenging and -generating pathways undergo strong global transcriptome changes in chickpea roots and nodules already 2 hours after onset of moderate salt stress (25mM NaCl). Additionally, a set of more than 15 candidate transcripts are proposed to be potential components of the salt overly sensitive (SOS) pathway in chickpea. Newly identified transcript isoforms are potential targets for breeding novel cultivars with high salinity tolerance. We demonstrate that these targets can be integrated into breeding schemes by micro-arrays and RT-PCR assays downstream of the generation of 26bp tags by SuperSAGE.
Vacuum-assisted closure (VAC) of complex infected wounds has recently gained popularity among various surgical specialties. The system is based on the application of negative pressure by controlled suction to the wound surface. The effectiveness of the VAC System on microcirculation and the promotion of granulation tissue proliferation are proved. In our case report we illustrate a scenario were a patient developed severe bleeding from the ascending aorta by penetration of wire fragments in the vessel. We conclude that all free particles in the sternum have to be removed completely before negative pressure is used.