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Nicht gut in Form : baulicher Zustand des Instituts für Sportwissenschaften lässt zu wünschen übrig
(2003)
Mit den beiden Herausgebern Klaus Herding und Otfried Schütz versucht Bettina Güdelhöfer, ... die "Geschichte" des Inventars zu rekapitulieren.
Vor wenigen Tagen ist die 50. Poetik-Gastdozentur an der Universität Frankfurt zu Ende gegangen. Wenn Elisabeth Borchers im Hörsaal VI über 'Lichtwelten' sprach, dann verkörperte sie das Prinzip dieser 'Vorlesungen': Seit 44 Jahren sprechen in Frankfurt bekannte deutschsprachige Autorinnen und Autoren über Literatur und über ihre eigenen Vorstellungen davon. Die 'Frankfurter Poetikdozentur' wurde über die Jahre zu einem Markenzeichen, das aus dem literarischen Leben Frankfurts wie Deutschlands nicht mehr wegzudenken ist. Anlass genug für einen kleinen Rückblick darauf, wie alles anfing.
Für viele Drogenprostituierte ist »die Szene« nicht nur Drogenmarkt, Arbeitsmarkt und Stätte des Konsums, sondern Lebensraum überhaupt, ein Lebensraum, in dem es allerdings mehr ums Überleben als ums Miteinanderleben geht. Wie Junkies, die Geld mit Prostitution verdienen, ihr Gewerbe betreiben, hat die Forschergruppe mit ihren 26 Interviews im Frankfurter Bahnhofsviertel ebenso beleuchtet wie Lebenswege, Perspektiven und Lebensträume der drogenabhängigen Prostituierten.
In Amerika wird Crack, eine rauchbare Form von Kokain, seit Mitte der 1980er Jahre konsumiert. In Deutschland wähnte man sich vor dieser »Ghetto-Droge« sicher. Doch seit Mitte der 1990er Jahre gibt es auch in Frankfurt und Hamburg Crack-Szenen. In der Main-Metropole war es zunächst eine kleine, von den Heroin-Süchtigen getrennte Raucherszene, aber schon 2002 hatte Crack das Kokain-Pulver völlig verdrängt und sogar das Heroin als bisher meistgebrauchte Droge auf den zweiten Rang verwiesen. Heute konsumieren 60 Prozent der Frankfurter Szene-Junkies mehrmals in der Woche Heroin, aber über 80 Prozent – oftmals dieselben Drogenabhängigen – auch mehrmals in der Woche Crack. Da bei dieser Droge der Kick zwar stark, aber nicht nachhaltig ist und die Junkies sich deshalb nie gesättigt fühlen, treibt die Abhängigen eine enorme Unruhe. Beobachtungen und Interviews mit Betroffenen zeigen, wie sich der Konsum dieser Droge verschärfend auf das Leben der Junkies und damit auf die gesamte Szene auswirkt.
Von Tops und Flops : wie die Universität Frankfurt beim ersten Forschungsranking abgeschnitten hat
(2003)
Vergangenes wird Gegenwart : Blick in die Arbeit des Theodor W. Adorno Archivs in Frankfurt am Main
(2003)
Ein Mathematiker mit universalem Anspruch : über Max Dehn und sein Wirken am Mathematischen Seminar
(2002)
Für eine erste Blüte der Mathematik in Frankfurt gab Max Dehn (1878 –1952) in den Jahren ab 1921 bis 1935 entscheidende Impulse. Seine völlig neuen Ideen zur Knotentheorie und zur Topologie beeinflussten die Entwicklung der Mathematik weit über Deutschland hinaus. 1935 fand sein Wirken in Frankfurt durch den Terror der Nationalsozialisten ein jähes Ende. Nach einer gefahrvollen Flucht über Norwegen, Finnland, die Sowjetunion und Japan erreichte Dehn schließlich, 62-jährig, die Vereinigten Staaten von Nordamerika. Eine seinen Fähigkeiten entsprechende Stellung konnte er dort nicht mehr erlangen. Sein fünfzigster Todestag in diesem Jahr ist Anlass für diese Rückschau.
Start frei für Start-Ups! : das Frankfurter Innovationszentrum Biotechnologie und sein Konzept
(2002)
Die »Metropolitana«, der »Planungsverband Frankfurt RheinMain«, die Olympiabewerbung, die »Wirtschaftsinitiative Frankfurt Rhein-Main« und der »Regionalpark Rhein-Main« sind Initiativen, die versuchen, das Rhein-Main-Gebiet für künftige Herausforderungen zu stärken. Zwar zählt diese Region zu den wirtschaftsstärksten Deutschlands, aber mit zunehmenden wirtschaftlichen Verflechtungen wird es für Städte und Regionen schwerer, sich im internationalen Wettbewerb um Unternehmensstandorte zu behaupten. Wird Frankfurt künftig im Konzert der »global cities« mitspielen können?
Warum ist die Entwicklung des Hochhausbaus in Deutschland anders verlaufen als in den USA? Warum hat Frankfurt im Gegensatz zu den übrigen deutschen Großstädten eine Skyline ausgebildet? In den USA waren Hochhäuser schon in den 1920er Jahren Symbole für den prosperierenden Kapitalismus. In Deutschland versuchte man einen anderen Weg: Hochhäuser ja, aber keine Zusammenballung in den Innenstädten. Was Städten wie München und Hamburg gelang, Hochhäuser nur ausnahmsweise zu genehmigen, führte in Frankfurt zu einer gegenläufigen Entwicklung – durch eine Politik, die unter dem Druck wirtschaftsstarker Unternehmen und Spekulanten immer wieder die Ausnahme von der Ausnahme genehmigte.
Umzug des Fachbereichs Physik steht bevor : das Stern-Gerlach-Zentrum für experimentelle Physik
(2004)
Spender sollen auch etwas davon haben : Spendierfreude über Identifikation mit Vorhaben steigern
(2002)
Wie lässt sich die finanzielle »Manövriermasse«, die die Vereinigung von Freunden und Förderern der Universität Frankfurt jährlich zur Verfügung stellen kann, erhöhen? Es ist ein schwieriges Geschäft, Menschen zum Spenden zu motivieren, das weiß der neue Vorsitzende der Vereinigung auch aus seinem Engagement im kulturellen Bereich. Doch eines erscheint Kopper dabei besonders wichtig: »Die Unterstützer sollen das Gefühl haben, dass es ein Geben und Nehmen ist.«
Das liberale Programm der Frankfurter Stiftungsuniversität und der Wille der Sponsoren, auch ungewöhnliche Berufungen, Experimente und Projekte zu fördern, zog ab 1914 innovative Gelehrte aller Disziplinen in die Main-Metropole. Pioniere ihres Fachs nutzten die Gunst der Stunde – so auch in der Physik, wo neben Friedrich Dessauer, dem Wegbreiter der Strahlenbiophysik, bedeutende Naturwissenschaftler die junge und in der wissenschaftlichen Welt noch hoch umstrittene Relativitätstheorie offensiv lehrten und in Experimenten fortführten. Erster Lehrstuhlinhaber für Theoretische Physik war der spätere Nobelpreisträger Max von Laue, ihm folgte mit Max Born ein weiterer Relativitätstheoretiker der ersten Stunde – und immerhin scheint auch Albert Einstein einen Wechsel von der Spree an den Main erwogen zu haben, wie ein erst kürzlich gefundenes Schreiben aus dem Jahr 1920 bestätigt.
Bernd Nothofer : 65 Jahre ; [Professor der Südostasienwissenschaften an der Universität Frankfurt]
(2007)
John Andrew Skillen : gestorben ; [ehem. Leiter des International Office der Universität Frankfurt]
(2007)
Irmtraud D. Wolcke-Renk : [Leiterin der Afrika-Abteilung der Universitätsbibliothek] gestorben
(2005)
Bilder der Anderen : die Digitalisierung des ethnographischen Bildarchivs des Frobenius-Instituts
(2006)
Poster presentation: Light is the main phase-adjusting stimulus of the circadian clock located in the suprachiasmatic nucleus (SCN). A candidate pathway transmitting photic information at the postsynaptic site in the SCN is the extracellular signal-regulated kinase (ERK 1/2) which has been previously shown to be an essential element in the photoentrainment of the circadian rhythm. An upstream activator of the ERK signalling route is the small intracellular GTPase Ras. Here we observed that endogenous Ras activity in the SCN was subjected to rhythmic changes, reaching maximum levels at the late subjective day and minimum levels at the late subjective night (CT22). In order to investigate if Ras would modulate the circadian cycle, we used transgenic mice expressing constitutively activated Val-12 Ha-Ras selectively in neurons (synRas mice). In these mice Ras activity was also cycling during the circadian rhythm yet, Ras activities were up-regulated at each time point measured. We investigated if this change in Ras activity translates into a behavioral phenotype by monitoring free-running activity rhythms under conditions of constant darkness. SynRas mice exhibited circadian rhythms in locomotor activities similar to WT mice. However, when challenged by applying a 15 minutes light pulse at CT22 to promote phase advance shifts, synRas mice were completely non-responsive. As a first step towards the possible intracellular mechanism of this behavioral change we analyzed ERK1/2 activities in more details: We found a 1,7-fold increase of circadian peak levels of ERK 1/2 activities at CT10 and CT14 in synRas mice, while at minimum levels (CT18, CT22) no differences were found between ERK1/2 activities of WT and synRas mice. In WT animals the 15 minutes light pulse at CT22 resulted in rapid up regulations of Ras, ERK1/2 and CREB activities as described previously by others. However, in correlation with the lack of a behavioral response, ERK1/2 but not Ras and CREB activities remained unchanged in synRas mice, suggesting that Ras-dependent and Ras-independent pathways may co-exist to regulate ERK1/2 and behavioral phase shifts in response to the acute light treatment. Next we investigated the length "tau" of the locomotor activity rhythm during constant darkness and found a slight shortening by about 10 minutes in synRas mice as compared to the WT littermates. Recently, "tau" has been discussed to be modulated by the interaction between glycogen synthase 3beta (GSK3beta) and a clock gene product (Per 2) that is involved in the determination of circadian phase durations. We describe here a down-regulation of GSK3beta phosphorylation in synRas mice as a possible mechanism of "tau" shortening. Taken together, cycling of Ras activity at elevated levels in the SCN during the circadian rhythm results in a distinct pattern of behavioral phenotype changes correlating with de-regulated ERK1/2 or GSK3beta activities.
Poster presentation: Hyperphosphorylation of tau is a characteristic of Alzheimer's disease (AD). Our group has established a model for tau hyperphosphorylation by mutating 10 residues from Ser/Thr to Glu to simulate the negative charge of phosphorylated residues ("pseudohyperphosphorylated (PHP)-tau"). In order to analyze temporal and spatial effects of hyperphosphorylation of tau in a systemic context, we have established transgenic mouse lines that express human wild-type (wt)- or PHP-tau under the control of the CamKIIalpha-promoter that leads to a forebrain specific moderate expression in neurons, i.e. the region where also tau-pathology in AD is abundant. For the evaluation of tau-induced changes in the transgenic mice, we quantified spine densities in the neocortex and hippocampus of transgenic mice. The spine densitiy was significantly increased in PHP-tau compared to wt-tau expressing mice. It is known that AD is associated with aberrant pre- and postsynaptic sprouting. Axonal sprouting is also observed in transgenic mice expressing mutated amyloid precursor protein (APP), which suggests that Abeta plays a significant role in this process. We deduce from our results, that (pseudo)-hyperphosphorylation of tau is sufficient to induce aberrant sprouting in the absence of Abeta. Analyses whether this sprouting is induced by pre- or postsynaptic changes and if functionally active synapses are formed are in progress. It will be interesting to determine if stabilization of these newly formed synapses slows or – in contrary – accelerates the progression of the disease. Sprouting as observed in our PHP-tau expressing mice is part of neuronal differentiation. One family of enzymes that is involved in cell differentiation are mitogen-acitvated protein kinases (MAPK). Western blot analysis was performed with brain lysates from transgenic mice to check whether PHP-tau induced sprouting is associated with MAPK activation. In fact, we also observed an increased activation of the MAPK ERK1/2 evident by phosphorylation of the residues Thr202 and Tyr204. ERK1/2 is also known to phosphorylate tau at sites characteristic for AD. Our results suggest the presence of a vicious circle by which (pseudo)-hyperphosphorylated tau activates ERK1/2 which in turn phosphorylates tau.
Poster presentation: Here we investigated the role of the amyloid precursor protein (APP) in regulation of Ca2+ store depletion-induced neural cell death. Ca2+ store depletion from the endoplasmic reticulum (ER) was induced by the SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) inhibitor thapsigargin which led to a rapid induction of the unfolded protein response (UPR) and a delayed activation of executioner caspases in the cultures. Overexpression of APP potently enhanced cytosolic Ca2+ levels and cell death after ER Ca2+ store depletion in comparison to vector-transfected controls. GeneChipR and RT-PCR analysis revealed that the expression of classical UPR chaperone genes was not altered by overexpression of APP.Interestingly, the induction of the ER stress-responsive pro-apoptotic transcription factor CHOP was significantly upregulated in APP-overexpressing cells in comparison to vectortransfected controls. Chelation of intracellular Ca2+ with BAPTA-AM revealed that enhanced CHOP expression after store depletion occured in a Ca2+-dependent manner in APPoverexpressing cells. Prevention of CHOP induction by BAPTA-AM and by RNA interference was also able to abrogate the potentiating effect of APP on thapsigargin-induced apoptosis. Application of the store-operated channel (SOC)-inhibitors SK F96365 and 2-APB downmodulated APP-triggered potentiation of cytosolic Ca2+ levels and apoptosis after treatment with thapsigargin. Our data demonstrate that APP-mediated regulation of ER Ca2+ homeostasis significantly modulates Ca2+ store depletion-induced cell death in a SOC- and CHOP-dependent manner, but independent of the UPR.
Poster presentation: The transcription factor NF-kappaB plays a pivotal role in the development and maintenance of the central nervous system and its constitutive activation in neurons has been previously reported. NF-kappaB is post-translationally activated upon phosphorylation of the IkappaBalpha inhibitory protein by the activated IkappaB kinase (IKKalpha/beta) and the subsequent degradation of IkappaBalpha by the proteasome. Recently, we had demonstrated an unexpected accumulation of three components of the NF-kappaB cascade in the axon initial segment (AIS): Activated IKK, phosphorylated IkappaBalpha and phosphorylated-p65(Ser536). These are all associated with detergent-insoluble cytoskeletal components of the AIS. We observed further compartimentalization as pIKKalpha/beta primarily associated with the membrane cytoskeleton, whereas pIkappaBalpha was sequestered to fasciculated microtubules. Colchicine-induced depolymerization of microtubules was associated with reduced sequestration of pIkappaBalpha in the AIS, which could be blocked by use of proteasome inhibitors like Mg-132 or Lactacystin. Concurrently, enhanced nuclear immunoreactivity for the NF-kappaB subunit p65 was noted. Using NF-kappaB-dependent reporter gene assays, a significant increase in NF-kappaB activity was observed after depolymerization of microtubules and this was inhibited by the microtubule-stabilizing drug paclitaxel. The use of transiently transfected, photoactivatable-GFP p65 fusion proteins will allow us to specifically analyse the compartimentalized signal transduction pathways in unique spatial and temporal resolution. Taken together, these observations provide strong evidence for compartmentalized activation of NF-kappaB in the AIS and modulation of neuronal NF-kappaB activity by microtubule dynamics.
Poster presentation: The mammalian pineal organ is a peripheral oscillator, depending on afferent information from the so-called master clock in the suprachiasmatic nuclei of the hypothalamus. One of the best studied outputs of the pineal gland is the small and hydrophobic molecule melatonin. In all vertebrates, melatonin is synthesized rhythmically with high levels at night, signalling the body the duration of the dark period. Changes or disruptions of melatonin rhythms in humans are related to a number of pathophysiological disorders, like Alzheimer's disease, seasonal affective disorder or the Smith-Magenis-Syndrome. To use melatonin in preventive or curative interferences with the human circadian system, a complete understanding of the generation of the rhythmic melatonin signal in the human pineal gland is essential. Melatonin biosynthesis is best studied in the rodent pineal gland, where the activity of the penultimate and rate-limiting enzyme, the arylalkylamine N-acetyltransferase (AA-NAT), is regulated on the transcriptional level, whereas the regulatory role of the ultimate enzymatic step, achieved by the hydroxyindole O-methyltransferase (HIOMT), is still under debate. In rodents, Aa-nat mRNA is about 100-fold elevated during the night in response to adrenergic stimulation of the cAMP-signalling pathway, with AA-NAT protein levels closely following this dynamics. In contrast, in all ungulates studied so far (cow, sheep), a post-transcriptional regulation of the AA-NAT is central to determine rhythmic melatonin synthesis. AA-NAT mRNA levels are constantly elevated, and lead to a constitutive up-regulation of AA-NAT protein, which is, however, rapidly degraded via proteasomal proteolysis during the day. AA-NAT proteolysis is only terminated upon the nocturnal increase in cAMP levels. Similar to ungulates, a post-transcriptional control of this enzyme seems evident in the pineal gland of the primate Macaca mulatta. Studies on the molecular basis of melatonin synthesis in the human being are sparse and almost exclusively based on phenomenological data, derived from non-invasive investigations. Yet the molecular mechanisms underlying the generation of the hormonal message of darkness can currently only be deciphered using autoptic material. We therefore analyzed in human post-mortem pineal tissue Aa-nat and Hiomt mRNA levels, AA-NAT and HIOMT enzyme activity, and melatonin levels for the first time simultaneously within tissue samples of the same specimen. Here presented data show the feasibility of this approach. Our results depict a clear diurnal rhythm in AA-NAT activity and melatonin content, despite constant values for Aa-nat and Hiomt mRNA, and for HIOMT activity. Notably, the here elevated AA-NAT activity during the dusk period does not correspond to a simultaneous elevation in melatonin content. It is currently unclear whether this finding may suggest a more important role of the ultimate enzyme in melatonin synthesis, the HIOMT, for rate-limiting the melatonin rhythm, as reported recently for the rodent pineal gland. Thus, our data support for the first time experimentally that post-transcriptional mechanisms are responsible for the generation of rhythmic melatonin synthesis in the human pineal gland.
Poster presentation: The transcription factor NF-kappaB plays a central role in the development and maintenance of the central nervous system and its constitutive activation in neurons has been repeatedly reported. Previous work from our laboratories (poster presentation: Compartimentalized NF-kappaB activity in the axon initial segment) had revealed an intriguing clustering of activated IKKalpha/beta and other downstream elements of an activated NF-kappaB cascade (phospho-IkappaBalpha, phospho-p65(Ser536)) in the axon initial segment (AIS). Accumulation of certain voltage-gated sodium channels (Na(v)1.2), M-type potassium channels (KCNQ2) as well as cytoskeletal anchoring proteins (AnkyrinG) characterise the AIS. However, it is not yet clear how AIS-localized IKK gets activated and whether this can be connected to the constitutive activation of NF-kappaB. Long-term blockade of sodium channels with tetrodotoxin, potassium-channels with linopirdine or NMDA-receptors with MK-801 did not elicit any change upon the constitutive activation of the pathway. Strikingly, the occurrence of phosphorylated IkappaBalpha was even unaltered by 24 h of incubation with protein synthesis inhibitors. Others have reported that impairment of NF-kappaB inhibits neuritogenesis. In this line we observed that the early initiation of IkappaBalpha phosphorylation was susceptible to inhibition of IKK in DIV1–2 neurons. We therefore aim to identify the interaction partners of the activated IKK complex in the AIS. Proteomic methods such as co-immunoprecipitation analyses and mass-spectrometry will help us to identify the key players in the initiation of constitutive IKK phosphorylation and activation in neurons.
Background Identification and evaluation of surface binding-pockets and occluded cavities are initial steps in protein structure-based drug design. Characterizing the active site's shape as well as the distribution of surrounding residues plays an important role for a variety of applications such as automated ligand docking or in situ modeling. Comparing the shape similarity of binding site geometries of related proteins provides further insights into the mechanisms of ligand binding. Results We present PocketPicker, an automated grid-based technique for the prediction of protein binding pockets that specifies the shape of a potential binding-site with regard to its buriedness. The method was applied to a representative set of protein-ligand complexes and their corresponding apo-protein structures to evaluate the quality of binding-site predictions. The performance of the pocket detection routine was compared to results achieved with the existing methods CAST, LIGSITE, LIGSITEcs, PASS and SURFNET. Success rates PocketPicker were comparable to those of LIGSITEcs and outperformed the other tools. We introduce a descriptor that translates the arrangement of grid points delineating a detected binding-site into a correlation vector. We show that this shape descriptor is suited for comparative analyses of similar binding-site geometry by examining induced-fit phenomena in aldose reductase. This new method uses information derived from calculations of the buriedness of potential binding-sites. Conclusions The pocket prediction routine of PocketPicker is a useful tool for identification of potential protein binding-pockets. It produces a convenient representation of binding-site shapes including an intuitive description of their accessibility. The shape-descriptor for automated classification of binding-site geometries can be used as an additional tool complementing elaborate manual inspections.
Neue Käfer vom Amur
(1879)
Referat gehalten am 5. März 1975 in Stuttgart anläßlich einer von der Deutschen Forschungsemeinschaft veranstalteten Arbeitstagung von Handschriftenbibliothekaren. Das Vortragsmanuskript wurde für den Druck leicht überarbeitet und um einige ausgewählte Literatur- und Abbiidunganachweise erweitert. Der Charakter einer thesenhaften Ubersichtsskizze, die der angestrebten Diskussion lediglich Themen zur näherne Erörterung aufweisen sollte, ist beibehalten.
Hubrilugus und Huwilogus
(1964)