bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML
Authors: Meyer Lüder H. , Queudeville Manon , Eckhoff Sarah M. , Creutzig Ursula , Reinhardt Dirk , Karawajew Leonid , Ludwig Wolf-Dieter , Stahnke Karsten , Debatin Klaus-Michael
Published: December 2007

Recently we reported that intact apoptosis signaling is indicative of favorable outcome in childhood acute lymphoblastic leukemia. Here we addressed this issue in 45 pediatric acute myeloid leukemia patients analyzing 2 core apoptogenic events: cytochrome c release and caspase-3 activation. In patients with good prognosis cytochrome c release was clearly found to be caspasedependent and correlated with activated caspase-3, indicating that activation of initiator or amplifier caspases such as caspase-8 together with an intact apoptosome function are elementary for favorable outcome. The functional integrity of this apoptogenic checkpoint is reflected by the parameter caspase-dependent cytochrome c-related activation of caspase-3 (CRACdep). Patients with positive CRACdep values (intact signaling) exhibited superior survival compared with CRACdep negative patients (deficient signaling). Thus, the propensity to undergo apoptosis of leukemia cells is an important feature for favorable treatment outcome and may serve as an additional stratification tool for pediatric AML patients. This trial was registered at www.ClinicalTrials.gov as #NCT00111345.
Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells
Authors: Ghiaur Gabriel , Ferkowicz Michael J. , Milsom Michael D. , Bailey Jeff , Witte David , Cancelas Jose A. , Yoder Mervin C. , Williams David A.
Published: December 2007

Definitive hematopoietic stem and progenitor cells (HSCs/Ps) originating from the yolk sac and/or para-aorta-splanchno-pleura/aorta-gonad-mesonephros are hypothesized to colonize the fetal liver, but mechanisms involved are poorly defined. The Rac subfamily of Rho GTPases has been shown to play essential roles in HSC/P localization to the bone marrow following transplantation. Here, we study the role of Rac1 in HSC/P migration during ontogeny and seeding of fetal liver. Using a triple-transgenic approach, we have deleted Rac1 in HSCs/Ps during very early embryonic development. Without Rac1, there was a decrease in circulating HSCs/Ps in the blood of embryonic day (E) 10.5 embryos, while yolk sac definitive hematopoiesis was quantitatively normal. Intraembryonic hematopoiesis was significantly impaired in Rac1-deficient embryos, culminating with absence of intra-aortic clusters and fetal liver hematopoiesis. At E10.5, Rac1-deficient HSCs/Ps displayed decreased transwell migration and impaired inter-action with the microenvironment in migration-dependent assays. These data suggest that Rac1 plays an important role in HSC/P migration during embryonic development and is essential for the emergence of intraembryonic hematopoiesis.
Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-κB–dependent DNA methyltransferase activity in acute myeloid leukemia
Authors: Liu Shujun , Liu Zhongfa , Xie Zhiliang , Pang Jiuxia , Yu Jianhua , Lehmann Esther , Huynh Lenguyen , Vukosavljevic Tamara , Takeki Mitsui , Klisovic Rebecca B. , Baiocchi Robert A. , Blum William , Porcu Pierluigi , Garzon Ramiro , Byrd John C. , Perrotti Danilo , Caligiuri Michael A. , Chan Kenneth K. , Wu Lai-Chu , Marcucci Guido
Published: December 2007

Bortezomib reversibly inhibits 26S proteasomal degradation, interferes with NF-κB, and exhibits antitumor activity in human malignancies. Zinc finger protein Sp1 transactivates DNMT1 gene in mice and is functionally regulated through protein abundance, posttranslational modifications (ie, ubiquitination), or interaction with other transcription factors (ie, NF-κB). We hypothesize that inhibition of proteasomal degradation and Sp1/NF-κB–mediated transactivation may impair aberrant DNA methyltransferase activity. We show here that, in addition to inducing accumulation of polyubiquitinated proteins and abolishment of NF-κB activities, bortezomib decreases Sp1 protein levels, disrupts the physical interaction of Sp1/NF-κB, and prevents binding of the Sp1/NF-κB complex to the DNMT1 gene promoter. Abrogation of Sp1/NF-κB complex by bortezomib causes transcriptional repression of DNMT1 gene and down-regulation of DNMT1 protein, which in turn induces global DNA hypomethylation in vitro and in vivo and re-expression of epigenetically silenced genes in human cancer cells. The involvement of Sp1/NF-κB in DNMT1 regulation is further demonstrated by the observation that Sp1 knockdown using mithramycin A or shRNA decreases DNMT1 protein levels, which instead are increased by Sp1 or NF-κB overexpression. Our results unveil the Sp1/NF-κB pathway as a modulator of DNA methyltransferase activity in human cancer and identify bortezomib as a novel epigenetic-targeting drug.
Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export
Authors: Gatza Michael L , Dayaram Tajhal , Marriott Susan J
Published: December 2007

Background

The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS). We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins.

Results

We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284) within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35.

Conclusion

This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284. Ubiquitination of these residues facilitates the dissociation of Tax from sc35-containing nuclear foci, and stimulates nuclear export of Tax through the CRM1 pathway.
Osteoblasts Cultured on Three‐Dimensional Synthetic Hydroxyapatite Implanted on a Chick Allantochorial Membrane Induce Ectopic Bone Marrow Differentiation
Authors: MANCINI LUCIA , TAMMA ROBERTO , SETTANNI MARIA , CAMERINO CLAUDIA , PATANO NICOLA , GRECO GIOVANNI , STRIPPOLI MAURIZIO , ZALLONE ALBERTA
Published: December 2007

Abstract:  Osteoblast (OB) activities have been studied on hydroxyapatite three‐dimensional (3D) scaffolds in comparison with traditional planar substrata. OBs cultured on 3D displayed increased proliferation, differentiation, and matrix protein synthesis, when compared to 2D cultures on the same substrata. Confluent cultures, however, could not be maintained for long, due to insufficient fluid diffusion within 3D scaffolds that impaired cell viability. Thus, confluent OB 3D cultures were implanted on the allantochorial membrane of chick embryos. Vessels from the embryo colonized the bone‐like network giving rise in the presence of OBs to an ectopic bone marrow formation in the intratrabecular spaces. In the absence of OBs, when the biomaterial alone was implanted, blood vessels were still present but hematopoietic marrow was absent. In both cases osteoclasts (OCs) derived from the host were found on the implant surface. These results indicated that scaffolds with cells can be easily vascularized and confirmed the role of OBs in the definition of the microenvironment that induce blood marrow differentiation in the intratrabecular spaces.
Androgens Promote Preosteoblast Differentiation via Activation of the Canonical Wnt Signaling Pathway
Authors: LIU XIN‐HUA , KIRSCHENBAUM ALEXANDER , YAO SHEN , LEVINE ALICE C.
Published: December 2007

Abstract:  Although androgens stimulate bone formation the precise events underlying these effects have not been elucidated. Wnt signaling plays a central role in osteoblast development and bone formation. We demonstrated that dihydrotestosterone (DHT) significantly stimulates MC3T3 preosteoblast differentiation with no effect on cell growth. This effect of DHT was accompanied by increased Wnt signaling in the same cells. Moreover, the stimulatory effects of DHT on preosteoblast differentiation were inhibited by overexpression of soluble frizzed‐related protein (sFRP), a naturally occurring Wnt antagonist. These results suggest that androgens promote preosteoblastic differentiation via effects on the canonical Wnt signaling pathway.
Control of Postnatal Bone Mass by the Zinc Finger Adapter Protein Schnurri‐3
Authors: GLIMCHER LAURIE H. , JONES DALLAS C. , WEIN MARC N.
Published: December 2007

Abstract:  The completed skeleton undergoes continuous remodeling for the duration of adult life. Rates of bone formation by osteoblasts and bone resorption by osteoclasts determine adult bone mass. Abnormalities in either the osteoblast or osteoclast compartment affect bone mass and result in skeletal disorders, the most common of which is osteoporosis, a state of low bone mass. Much is known about the molecular control of bone formation and resorption from rare single gene disorders resulting in elevated or reduced bone mass. Such genetic disorders can be attributed either to osteoclast deficiencies, collectively termed “osteopetrosis,” or to intrinsically elevated osteoblast activity, termed “osteosclerosis.” However, an increasing need for anabolic therapies to prevent age‐induced bone loss has stimulated a search for additional genes that act at the level of the osteoblast to regulate matrix synthesis. Recently, we have discovered a zinc finger adaptor protein called Schnurri‐3 (Shn3) that potently regulates adult bone mass. Mice that lack Shn3 have normal skeletal morphogenesis but display profoundly elevated bone mass that increases with age. The molecular mechanism was revealed to be the recruitment of WWP1, a Nedd4 family E3 ubiquitin ligase, by Shn3 to the major transcriptional regulator of the osteoblast, Runx2. In the absence of Shn3, Runx2 degradation by WWP1 is inhibited resulting in increased levels of Runx2 protein and enhanced expression of Runx2 target genes leading to increased osteoblast synthetic activity. Small molecules that inhibit Shn3 or WWP1 may be attractive candidates for the treatment of diseases of low bone mass.
Parathyroid Hormone Stimulation of Noncanonical Wnt Signaling in Bone
Authors: BERGENSTOCK MARIKA K. , PARTRIDGE NICOLA C.
Published: December 2007

Abstract:  In bone, parathyroid hormone (PTH) exerts either a catabolic or an anabolic effect depending on its method of administration. This paradoxical action has led to the use of PTH as an effective treatment for osteoporosis. The Wnt family of signaling proteins has a critical role in multiple events, which are necessary for proper animal development and survival, yet their exact method of action in bone remains elusive. We have uncovered a novel link between Wnt‐4 and PTH. We think that, in bone, Wnt‐4 signaling in response to PTH implicates cross‐talk of multiple signaling pathways. This work hopes to further elucidate Wnt signaling in bone and provide greater understanding of PTH's anabolic effects in bone.
The PTHrP Functional Domain Is at the Gates of Endochondral Bones
Authors: BROADUS ARTHUR E. , MACICA CAROLYN , CHEN XUESONG
Published: December 2007

Abstract:  PTHrP gene‐expression products are generally of very low abundance. The PTHrP‐lacZ knockin mouse is a useful tool in this regard, identifying PTHrP expression in previously unrecognized sites and serving to score this expression in gene‐regulation experiments. These sites include the periosteum and ligament/tendon insertion sites at the surface of endochondral bones, in which PTHrP appears to regulate subjacent bone cell populations. As mesenchymal condensations chondrify, PTHrP/lacZ is also expressed in epiphyseal cartilage (the chondroepiphysis), and this structure contributes PTHrP‐expressing chondrocyte populations to both articular cartilage and growth‐plate cartilage when these structures take shape postnatally. The Indian hedgehog‐PTHrP axis is fully deployed in both of these locations and in articular cartilage appears to protect the joint space from invasion by mineralizing cells. In most of these sites PTHrP is mechanically regulated.
Selective mobilization of fatty acids from adipose tissue in migratory birds
Authors: Price Edwin R. , Krokfors Anna , Guglielmo Christopher G.
Published: December 2007

During times of high energy demand, stored fatty acids are mobilized from adipocytes. This mobilization has previously been shown to be a non-random process, with more hydrophilic fatty acids being mobilized most readily. The objectives of this study were to characterize the relative mobilization of fatty acids from adipocytes in two migratory bird species and to investigate possible changes in selective fatty acid mobilization associated with the migratory period. Captive ruffs (Philomachus pugnax) and white-crowned sparrows (Zonotrichia leucophrys) were studied. The sparrows were divided into two treatments: `winter' (photoperiod 8 h:16 h L:D)and `migrant' (in which migratory condition was induced with a photoperiodic manipulation of 8 h:16 h L:D, followed by 16 h:8 h L:D). Adipose tissue was removed from ruffs and sparrows and incubated for 90 min after stimulation with epinephrine. The proportions of individual fatty acid species released into the incubation medium were compared with their proportions in the adipocytes to determine relative mobilizations. We found that patterns of relative mobilization in ruffs and sparrows are similar to those of mammals,with shorter chain lengths and more double bonds leading to higher relative mobilization. Seasonal condition in sparrows did not alter this pattern. This pattern of relative mobilization from adipocytes seems to be a general rule amongst birds and mammals and should be considered before inferring functionality about selective retention or mobilization of certain fatty acids. The composition of adipose stores in birds may affect migratory performance; however, our results indicate that patterns of relative mobilization at the adipocytes do not vary with season in migratory birds.
Fire Resistance of Reinforced Concrete Columns with Square Cross Section
Authors: Wu Bo , Hong Zhou , Tang Gui-He , Wang Chao
Published: December 2007

Calculation of the fire resistance of 480 square cross section normal strength concrete (NSC) columns and 480 high strength concrete (HSC) columns, made with siliceous aggregate, is presented in this paper. The variables considered in the study include concrete strength (NSC and HSC), dimension of column cross section, axial load ratio, load eccentricity ratio (i.e., ratio of load eccentricity to dimension of column cross section), and steel ratio (i.e., ratio of longitudinal reinforcement to cross-sectional area of column). Explosive spalling of HSC exposed to fire is also considered approximately. Simulation results show that: (1) increasing the dimension of column cross section, reducing the axial load ratio, and reducing the load eccentricity ratio are all effective measures for improving the fire resistance of both NSC and HSC columns subjected to concentric axial load or eccentric axial load; (2) increasing the steel ratio has no significant influence on the fire resistance of concentrically loaded NSC and HSC columns, but has some positive effect on the fire resistance of eccentrically loaded NSC and HSC columns; (3) explosive spalling of HSC has a significant detrimental influence on the fire resistance of HSC columns. Based on simulation results, a simplified formula is empirically developed to enable determination of the fire resistance of both NSC and HSC columns, and is shown to be applicable to concrete columns with square cross section.
Boundary Element Analysis of Coupled Continuum and Skeletal Structures
Authors: Rashed Youssef F.
Published: December 2007

This paper presents a new technique for solving coupled continuum and skeletal structures. The technique is based on employing the well-known flexibility and stiffness methods within the boundary element method (BEM). The analyzed problem is divided into: continuum parts, which are modeled using the BEM and skeletal parts which are modeled using the flexibility or stiffness methods. The main idea of the presented technique is to set up a methodology to generate flexibility or stiffness matrices for the continuum parts using the BEM. To do so, several flexibility and stiffness models are developed. The developed technique is tested on three problems. Results are compared to those obtained from the finite element method (FEM) to show the validity of the developed technique. The present technique gains both advantages of the BEM and the FEM as it allows boundary-only discretization for the continuum parts and uses the banded assembly technique of FEM for the overall structure.
Blast Testing of RC Slabs Retrofitted with NSM CFRP Plates
Authors: Wu Chengqing , Oehlers Deric John , Wachl John , Glynn Craig , Spencer Adrian , Merrigan Matthew , Day Ian
Published: December 2007

In this paper, blast testing was performed on two reinforced concrete specimens: a plain reinforced concrete (RC) specimen; and an identical RC specimen retrofitted with near surface mounted (NSM) carbon fibre reinforced polymer (CFRP) plates. Each specimen was subjected to two separate explosive loads at a standoff distance of 0.6m, with the aim of investigating the performances of both specimens within both their elastic and plastic response ranges. The first blast (Blast 1) and second blast (Blast 2) consisted of an equivalent TNT charge weight of 0.079kg and 2.09kg respectively. The elastic-range responses of both specimens after the small shot (Blast 1), such as acceleration and deflection were obtained and comparisons were made between the specimens. The plastic performances of both specimens, such as tension face scabbing, crack patterns, plastic hinges and permanent deflection, after the large shot (Blast 2) were also analysed and compared. A number of unique failures and behaviours of both specimens were observed, investigated and analyzed. The test results provide a vital direction in the development of an optimal retrofit in future research.
Behaviour of High Strength Concrete-Filled Slender RHS Steel Tubes
Authors: Zhang Sumei , Guo Lanhui
Published: December 2007

An experimental study of the behaviour of high strength concrete-filled slender rectangular hollow section (RHS) tubes under the combined actions of axial compression and bending moment is presented. A total of 26 specimens were tested. The main parameters considered in the test were slenderness ratio, depth-to-breadth ratio, steel-to-concrete area ratio and eccentricity-to-depth ratio. The experimental results showed that the ultimate capacity of test specimens decreased rapidly with increase of slenderness ratio and eccentricity-to-depth ratio. For the specimens with depth-to-thickness ratio larger than 50, local buckling failure occurred prior to the ultimate capacity. A nonlinear analysis program, BC, was developed to analyze the behaviour of high strength concrete-filled RHS tubes. A comparison for ultimate capacity showed that the theoretical results agreed very well with the experimental results. The depth-to-breadth ratio (varying from 1.0 to 1.6) showed little influence on the stability capacity of the specimens. The comparison of the experimental results with the results calculated by the design equations in the codes, such as LRFD, EC4 and AIJ showed that EC4 closely predicts the ultimate capacity of the specimens.
Bending Moment Prediction for Continuous Composite Beams by Neural Networks
Authors: Chaudhary Sandeep , Pendharkar Umesh , Nagpal Ashok Kumar
Published: December 2007

A methodology has been developed for the continuous composite beams to predict the inelastic bending moments (considering the cracking of concrete) from the elastic moments (neglecting the cracking) by using the neural networks. The proposed neural network models predict the inelastic moment ratios (ratio of inelastic moment to elastic moment) at the supports of a span. Nine significant structural parameters have been identified governing the inelastic moment ratios. Six neural networks have been presented to cover the entire practical range of the beams. The proposed neural networks have been validated for a number of beams with different number of spans and the errors are shown to be small for practical purposes. The methodology enables rapid estimation of inelastic moments. The methodology can easily be extended for large composite building frames where a very significant saving in computational effort would result. The feasibility of the methodology for building frames has been demonstrated by considering a single story frame.
The bacterial toxin RelE induces specific mRNA cleavage in the A site of the eukaryote ribosome
Authors: Andreev Dmitri , Hauryliuk Vasili , Terenin Ilya , Dmitriev Sergey , Ehrenberg Måns , Shatsky Ivan
Published: December 2007

RelE/RelB is a well-characterized toxin–anti-toxin pair involved in nutritional stress responses in Bacteria and Archae. RelE lacks any eukaryote homolog, but we demonstrate here that it efficiently and specifically cleaves mRNA in the A site of the eukaryote ribosome. The cleavage mechanism is similar to that in bacteria, showing the feasibility of A-site cleavage of mRNA for regulatory purposes also in eukaryotes. RelE cleavage in the A-site codon of a stalled eukaryote ribosome is precise and easily monitored, making “RelE printing” a useful complement to toeprinting to determine the exact mRNA location on the eukaryote ribosome and to probe the occupancy of its A site.
Proteasomal degradation of human release factor eRF3a regulates translation termination complex formation
Authors: Chauvin Céline , Jean-Jean Olivier
Published: December 2007

In eukaryotes, eRF1 and eRF3 are associated in a complex that mediates translation termination. The regulation of the formation of this complex in vivo is far from being understood. In mammalian cells, depletion of eRF3a causes a reduction of eRF1 level by decreasing its stability. Here, we investigate the status of eRF3a when not associated with eRF1. We show that eRF3a forms altered in their eRF1-binding site have a decreased stability, which increases upon cell treatment with the proteasome inhibitor MG132. We also show that eRF3a forms altered in eRF1 binding as well as wild-type eRF3a are polyubiquitinated. These results indicate that eRF3a is degraded by the proteasome when not associated with eRF1 and suggest that proteasomal degradation of eRF3a controls translation termination complex formation by adjusting the eRF3a level to that of eRF1.
The E. coli RhlE RNA helicase regulates the function of related RNA helicases during ribosome assembly
Authors: Jain Chaitanya
Published: December 2007

Escherichia coli contains five members of the DEAD-box RNA helicase family, a ubiquitous class of proteins characterized by their ability to unwind RNA duplexes. Although four of these proteins have been implicated in RNA turnover or ribosome biogenesis, no cellular function for the RhlE DEAD-box protein has been described as yet. During an analysis of the cold-sensitive growth defect of a strain lacking the DeaD/CsdA RNA helicase, rhlE plasmids were identified from a chromosomal library as multicopy suppressors of the growth defect. Remarkably, when tested for allele specificity, RhlE overproduction was found to exacerbate the cold-sensitive growth defect of a strain that lacks the SrmB RNA helicase. Moreover, the absence of RhlE exacerbated or alleviated the cold-sensitive defect of deaD or srmB strains, respectively. Primer extension and ribosome analysis indicated that RhlE regulates the accumulation of immature ribosomal RNA or ribosome precursors when deaD or srmB strains are grown at low temperatures. By using an epitope-tagged version of RhlE, the majority of RhlE in cell extracts was found to cosediment with ribosome-containing fractions. Since both DeaD and SrmB have been recently shown to function in ribosome assembly, these findings suggests that rhlE genetically interacts with srmB and deaD to modulate their function during ribosome maturation. On the basis of the available evidence, I propose that RhlE is a novel ribosome assembly factor, which plays a role in the interconversion of ribosomal RNA-folding intermediates that are further processed by DeaD or SrmB during ribosome maturation.
Global analysis of mRNA splicing
Authors: Moore Michael J. , Silver Pamela A.
Published: December 2007

Alternative mRNA splicing is a rich source of transcript diversity in eukaryotic cells with broad roles in development and disease. Systems-wide experimental methods have started to define how global splicing regulation shapes complex biological properties and pathways. Here, we review these approaches, describe recent insights they have yielded, and discuss avenues of future investigation.
Johannes Ullmaier, Von Acid nach Adlon und zurück. Eine Reise durch die deutschsprachige Popliteratur. Mit einer illustrierten Bibliographie zu 40 Jahren deutschsprachiger Pop- und Beatliteratur. 2001 – Heinz Ludwig Arnold / Jörgen Schäfer (Hgg.), Pop-Literatur. 2003 – Jochen Bonz (Hg.), Popkulturtheorie. 2002
Authors: Conter Claude D.
Published: December 2007

Pop und populäre Kultur sind seit der Gründung des „Centre for Contemporary Cultural Studies“ 1964 in Birmingham ein akademischer Forschungsgegenstand, der nach 40 Jahren aber noch keine konzisen, an historischen Prozessen orientierte Theoriekonzepte vorweist, geschweige denn grundsätzliche Fragen nach den Gegenständen der Populärkultur und Abgrenzungen zur Gesamtkultur geklärt hat. Mit der in den 90er Jahren entfachten Diskussion um die Kulturwissenschaften hat die Erforschung der populären Kultur in Deutschland allerdings Konjunktur. Einen Überblick der Forschung beabsichtigt daher das jüngst erschienene Handbuch Populäre Kultur, das nach bisherigen überwiegend soziologischen Fragestellungen vor allem die ästhetische Funktion populärer Kultur erschließen will. Daß die Literatur dabei keinen eigenständigen Eintrag erhalten hat, wird mit dem nicht ganz nachvollziehbaren Argument begründet, daß die jeweilige Fachdisziplin die populärkulturelle Dimension herausarbeiten würde – ein für ein interdisziplinäres Handbuch eher befremdliches Argument. Die Literaturwissenschaft hat sich nun aber tatsächlich, verstärkt in den vergangenen drei Jahren, des Themas der sogenannten Popliteratur angenommen und dabei erstens auf die heftigen Debatten über die ‚neue Lesbarkeit‘ in den Feuilletons seit dem Erscheinen von Christian Krachts Roman Faserland reagiert und zweitens in diesem Kontext Fragen nach dem Verhältnis von E- und U-Kultur seit den 60er Jahren wieder neu gestellt.
Peter O. Chotjewitz, Machiavellis letzter Brief. Historischer Roman. 2003
Authors: Langer Daniela
Published: December 2007

Chotjewitz' neuer Roman läßt sich im besten Sinne als postmodern bezeichnen, faßt man als Kennzeichen postmodernen Schreibens Selbstreflexivität, Intertextualität und einen historischen Bezug im gleichzeitigen Spiel mit Fakt und Fiktion. Wie in Ecos Der Name der Rose, so liegt auch hier der Stoff einige Jahrhunderte zurück, schickt doch Chotjewitz den Zittauer Poeten Christian Weise im Jahre 1664 auf eine fiktive Reise nach Italien, um im Auftrag des Herzogs August von Braunschweig-Wolfenbüttel das Manuskript von ‚Machiavellis letztem Brief‘ für die Wolfenbütteler Bibliothek zu erwerben. Beginnt Adson bei Eco mit einem Bibelzitat (Joh 1,1), so auch der Ich-Erzähler Weise bei Chotjewitz (Gen 1,1); und setzt die eigentliche Handlung von Il nome della rosa mit einem ausgewiesenen literarischen Klischee an („Era una bella mattina di fine novembre“), so steht Machiavellis letzter Brief, als Binnenerzählung eingefügt, dem nicht nach: „Der Sturm riß eine drei Kilometer breite Schneise der Verwüstung in die Toskana vom adriatischen bis zum etruskischen Meer, als Cosimo Anfang Oktober 1434 zurückkehrte“ (S. 162).
Sonja Emmerling, Geschlechterbeziehungen in den Gawan-Büchern des „Parzival“. Wolframs Arbeit an einem literarischen Modell. 2003
Authors: Yeandle David N.
Published: December 2007

Die vorliegende Arbeit ist eine leicht überarbeitete Augsburger Dissertation vom Wintersemester 2001. Sie bietet sowohl in systematischer als auch in sachlicher Hinsicht eine Fülle von neuen Einsichten in Wolframs Gralroman und ist somit sehr zu begrüßen. Der Titel täuscht etwas, denn zwar handeln die ersten 200 Seiten vorwiegend von den Gawan-Büchern, die folgenden 100 Seiten jedoch befassen sich hauptsächlich mit den Gahmuret- und Parzival-Büchern. Der Vergleich der drei Partien des Romans ist aber durchaus gerechtfertigt. Zudem finden sich in beiden Teilen des Buchs wichtige Interpretationen von Einzelaspekten der Handlung, die nicht immer direkt auf die Geschlechterbeziehungen bezogen sind, vielmehr als ‚interpretatorischer Kommentar‘ allgemein herangezogen werden können. Alle diese neuen Einsichten oder auch sämtliche Stellen, an denen man auch anderer Meinung sein könnte, zu besprechen, ist hier nicht möglich, daher werden wir uns auf die Hauptergebnisse der Studie konzentrieren müssen.
Dagmar Giersberg, „Je comprends les Werther“. Goethes Briefroman im Werk Flauberts. 2003
Authors: Helmreich Christian
Published: December 2007

Schon den Zeitgenossen ist die große Bewunderung aufgefallen, die Flaubert (1821–1880) Goethe entgegenbrachte. Eine systematische Analyse der Beziehung zwischen Flaubert und Goethe, die über die Auswertung von Flauberts Briefwechsel oder über das Auffinden von mehr oder weniger auffälligen Analogien zwischen den beiden Autoren hinausginge, fehlt gleichwohl. Einen Teil dieses Massivs wird nun von Dagmar Giersberg erschlossen, die in ihrer 2003 erschienenen Untersuchung Flauberts Auseinandersetzung mit den Leiden des jungen Werthers nachzeichnet. Insbesondere in den Jugendwerken Flauberts bis hin zu Madame Bovary sind die mehr oder weniger offenen Hinweise auf Goethes Briefroman kaum zu übersehen. In ihrer überaus sorgfältigen Arbeit, die mit dem Begriff der Intertextualität operiert (eine methodologische Option, auf die abschließend noch zurückzukommen sein wird) untersucht Giersberg in je eigenen Kapiteln Les Mémoires d'un fou (1838), Novembre (1840–1842), die erste, zu Lebzeiten Flauberts unveröffentlichte Fassung von L'Éducation sentimentale (1845), Madame Bovary (1857) und die ‚zweite‘ (1869 publizierte) Éducation sentimentale: „Gezeigt werden soll, daß die gelesenen Erzählungen und Romane Flauberts als Spiele mit der Vorlage Werther verstanden werden können“ (S. 11). Interessanterweise begnügt sich die Arbeit nicht damit, den ‚Einfluß‘ Goethes auf Flauberts Œuvre festzustellen und die einschlägigen Parallelstellen aufzuführen. Überzeugend wird in textnah gehaltenen Analysen herausgearbeitet, wie Flaubert dem Goetheschen Briefroman bald einige seiner zentralen Themen, bald einzelne Motive, bald formale Elemente entnimmt und umfunktioniert.
Stefan Willer, Poetik der Etymologie. Texturen sprachlichen Wissens in der Romantik. 2003
Authors: Klausnitzer Ralf
Published: December 2007

Die vorliegende Dissertation, im Frühjahr 2001 in Münster verteidigt, stellt sich ein ehrgeiziges Ziel. Sie will als „dezidiert poetologisch verfahrende Wissensgeschichte“ (S. IX) das „romantische Wissen über Sprache“ systematisch aufarbeiten und dabei eine Forschungslücke schließen, die in der Einleitung konstatiert wird. Dort heißt es: „Jenseits von Sprachphilosophie, Geschichte der Nationalphilologie und der Untersuchung der Sprachästhetik literarischer Texte gibt es bislang kaum Ansätze einer systematischen Aufarbeitung des spekulativen Sprachdenkens der Romantik, wie es in besonderer Weise von der Theorie und Praxis der Etymologie repräsentiert wird“ (ebd.). Mit diesem Vorhaben widmet sich der Autor einem Gegenstandsbereich, der schon von Ernst Behler als „virtually unknown“ beschrieben wurde und dessen besondere Problematik aus den nicht selten nur fragmentarischen, nur schwer auf eine einheitliche Vorstellung zu beziehenden Äußerungen der rege produzierenden Akteure erwächst.
Karin Bohnert, Bildnisse auf der Bühne. Zur dramatischen Funktion des gemalten Porträts in europäischen Bühnenstücken. 2003
Authors: Schmitz-Emans Monika
Published: December 2007

In einer erheblichen Zahl von dramatischen Werken spielen gemalte Bilder, und hier vor allem Porträts, eine für die Handlung konstitutive Rolle. Karin Bohnerts Monographie stellt über 30 solcher Werke ausführlich sowie diverse weitere in knapperer Form vor, mehrheitlich deutsch-sprachige, aber auch englische, französische sowie einzelne italienische (Gozzi, Pirandello) und norwegische (Ibsen), in der Mehrzahl bekannte, aber auch weniger bekannte wie Kotzebues Die Großmamma und Ernst von Houwalds inhaltlich besonders einschlägiges Drama Das Bild. Erkenntnisinteresse und Prämissen der vergleichenden Untersuchung werden einleitend so klar wie einleuchtend dargelegt: In literarischen Texten haben, so Bohnert, Porträts einen besonderen Status, der sich insbesondere aus tradierten bildmagischen Vorstellungen ableiten läßt.
Birgit Röder, A Study of the Major Novellas of E. T. A. Hoffmann. 2003
Authors: Vinardell Teresa
Published: December 2007

Die Autorin des vorliegenden Bandes untersucht, wie der Konflikt zwischen dem metaphysischen Reich der Ideen und der Welt des Alltags in einigen Werken Hoffmanns zum Ausdruck kommt. Die Textgrundlage bilden insgesamt acht Erzählungen, vier aus den Serapions-Brüdern und vier aus den Fantasie- und Nachtstücken, wobei sich die Autorin aus dieser etwas willkürlichen Auswahl einen nicht näher präzisierten Überblick („representative selection“, S. 7) verspricht. So ist es schon erstaunlich, daß sie dabei einige Texte völlig außer acht läßt, die, wie namentlich Der goldne Topf aus den Fantasiestücken, sowohl die Dichotomie zwischen philisterhaftem Diesseits und phantastischem Jenseits als auch deren Ineinanderwachsen meisterhaft darlegen. Generell ist an Röders Studie auszusetzen, daß sie sich auf die unten genannten Erzählungen Hoffmanns beschränkt und nur selten auf andere seiner Werke Bezug nimmt, die ebenfalls den erwähnten Widerspruch zwischen Ideal und Wirklichkeit thematisieren und deren Berücksichtigung der vorliegenden Analyse mehr Tiefe und inneren Zusammenhang verliehen hätte. Erfreulich ist allerdings, daß Röder auch Texte bespricht, denen man bislang nicht genügende Aufmerksamkeit geschenkt hatte (z. B. Der Artushof).
Carsten Strathausen, The Look of Things. Poetry and Vision around 1900. 2003
Authors: Fick Monika
Published: December 2007

Die Textbasis von Strathausens Studien zur Literatur der Jahrhundertwende ist schmal. Analysiert werden einige wenige Gedichte von Rilke (zentral: Früher Apollo, Eingang und Die Gazelle), Hofmannsthal (zentral: Vorfrühling) und George (zentral: Der Teppich und Urlandschaft); hinzu treten Ein Brief und der Malte-Roman, welche als Prosawerke selektiv zur Untermauerung der Beobachtungen herangezogen werden. Relativ knapp lassen sich diese zusammenfassen: Strathausens Interesse gilt dem Versuch des Ästhetizismus, mittels der autonom gewordenen Sprache eine verdichtete Welt zu evozieren. Zugleich stellt er sich dem Anspruch der emphatischen Moderne, nach dem Zusammenbruch der metaphysischen Systeme eine neue, andere, nicht mehr geist- und subjektbestimmte „Primärwirklichkeit“ sprachlich zu erzeugen. Für die behandelten Texte und Autoren bedeutet dies: Zum einen umkreist Strathausen in immer neuen Anläufen, wie eine Wahrheit des Lebens und eine unmittelbare „Anschauung“ der Dinge sich in der Sprache der Gedichte artikulieren und Gestalt annehmen. Die besondere Signatur dieser Wahrheit sieht er in der Zersprengung des idealistischen Subjekts zugunsten der Präsenz des Körpers. Zum anderen deckt er auf, wie der sprachreflexive Gestus der Gedichte diese „Offenbarung“ von Wahrheit, Leben und Wesen der Dinge ständig durchkreuzt und aufhebt. An der Wurzel der Einheit von Sprache und Sein werde die sprachliche Setzung sichtbar.
Enduring Paradigm, New Opportunities: The Value of the Archival Perspective in the Digital Environment Collections, Content, and the Web
Authors: Smith Steve
Published: December 2007

Shades of Greek mythology: around 1980, the Council on Library Resources (CLR) created the Committee on Preservation and Access, which shortly there-after gained independence as the Commission on Preservation and Access (CPA). For fifteen years the CPA was a principle advocate for and recognized leader of national preservation activities, in addition to promoting preservation research and international preservation activities. In 1997, CLR and CPA merged to form the Council on Library and Information Resources (CLIR), which not only maintained most of the activities of CLR and CPA, but also became the administrative home to the Digital Library Federation.
Regulated β-Cell Regeneration in the Adult Mouse Pancreas
Authors: Cano David A. , Rulifson Ingrid C. , Heiser Patrick W. , Swigart Lamorna B. , Pelengaris Stella , German Mike , Evan Gerard I. , Bluestone Jeffrey A. , Hebrok Matthias
Published: December 2007

Several studies have shown that the adult pancreas possesses a limited potential for β-cell regeneration upon tissue injury. One of the difficulties in studying β-cell regeneration has been the lack of a robust, synchronized animal model system that would allow controlled regulation of β-cell loss and subsequent proliferation in adult pancreas. Here we present a transgenic mouse regeneration model in which the c-Myc transcription factor/mutant estrogen receptor (cMycERTAM) fusion protein can be specifically activated in mature β-cells. We have studied these transgenic mice by immunohistochemical and biochemical methods to assess the ablation and posterior regeneration of β-cells. Activation of the cMycERTAM fusion protein results in synchronous and selective β-cell apoptosis followed by the onset of acute diabetes. Inactivation of c-Myc leads to gradual regeneration of insulin-expressing cells and reversal of diabetes. Our results demonstrate that the mature pancreas has the ability to fully recover from almost complete ablation of all existing β-cells. Our results also suggest the regeneration of β-cells is mediated by replication of β-cells rather than neogenesis from pancreatic ducts.
Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS–Mediated Signaling
Authors: Calvert John W. , Gundewar Susheel , Jha Saurabh , Greer James J.M. , Bestermann William H. , Tian Rong , Lefer David J.
Published: December 2007

OBJECTIVE—Clinical studies have reported that metformin reduces cardiovascular end points of type 2 diabetic subjects by actions that cannot solely be attributed to glucose-lowering effects. The therapeutic effects of metformin have been reported to be mediated by its activation of AMP-activated protein kinase (AMPK), a metabolite sensing protein kinase whose activation following myocardial ischemia has been suggested to be an endogenous protective signaling mechanism. We investigated the potential cardioprotective effects of a single, low-dose metformin treatment (i.e., 286-fold less than the maximum antihyperglycemic dose) in a murine model of myocardial ischemia-reperfusion (I/R) injury.

RESEARCH DESIGN AND METHODS—Nondiabetic and diabetic (db/db) mice were subjected to transient myocardial ischemia for a period of 30 min followed by reperfusion. Metformin (125 μg/kg) or vehicle (saline) was administered either before ischemia or at the time of reperfusion.

RESULTS—Administration of metformin before ischemia or at reperfusion decreased myocardial injury in both nondiabetic and diabetic mice. Importantly, metformin did not alter blood glucose levels. During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased endothelial nitric oxide (eNOS) phosphorylation at residue serine 1177.

CONCLUSIONS—These findings provide important information that myocardial AMPK activation by metformin following I/R sets into motion events, including eNOS activation, which ultimately lead to cardioprotection.
The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes
Authors: Cherney David Z.I. , Miller Judith A. , Scholey James W. , Bradley Timothy J. , Slorach Cameron , Curtis Jaqueline R. , Dekker Maria G. , Nasrallah Rania , Hébert Richard L. , Sochett Etienne B.
Published: December 2007

OBJECTIVE—Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. We hypothesized that COX2 inhibition would alleviate the hyperfiltration state and would abrogate the hyperglycemia-mediated rise in glomerular filtration rate (GFR).

RESEARCH DESIGN AND METHODS—Renal function was assessed during clamped euglycemia and hyperglycemia on 2 consecutive days before and then again after 14 days of COX2 inhibition using 200 mg celecoxib once daily by mouth. For analysis, the cohort was then divided into two groups based on the baseline GFR: 9 subjects exhibited hyperfiltration (GFR ≥135 ml/min per 1.73 m2), and 12 subjects exhibited normofiltration (GFR <135 ml/min per 1.73 m2).

RESULTS—Under euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the hyperfiltration group (150 ± 5 to 139 ± 5 ml/min per 1.73 m2) but increased GFR in the normofiltration group (118 ± 5 to 138 ± 5 ml/min per 1.73 m2). COX2 inhibition did not blunt the hyperglycemia-associated rise in GFR in the normofiltration group and was instead associated with an augmented rise in GFR.

CONCLUSIONS—In summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 diabetes. The renal response to COX2 inhibition emphasizes that hyperfiltration and normofiltration are distinct physiological states.
Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control
Authors: Kolavennu Vasantha , Zeng Lixia , Peng Hui , Wang Yin , Danesh Farhad R.
Published: December 2007

OBJECTIVE—RhoA, a small GTPase protein, and its immediate downstream target, Rho kinase (ROCK), control a wide variety of signal transduction pathways. Recent studies have shown that fasudil, a selective ROCK inhibitor, may play a pivotal role in a number of pathological conditions, ranging from cardiovascular diseases to pulmonary hypertension and erectile dysfunction. Considerable evidence suggests that some of the beneficial effects of statins may also stem from their modulatory effects on RhoA/ROCK signaling. In the current study, we hypothesized that pharmacological blockade of the RhoA/ROCK pathway with either fasudil or simvastatin would ameliorate progression of diabetic nephropathy.

RESEARCH DESIGN AND METHODS—In two separate experiments, diabetic db/db mice received fasudil (10 mg · kg− · day− i.p.) or simvastatin (40 mg · kg− · day− p.o.) for 16 weeks. Untreated db/db and db/m mice served as controls.

RESULTS—The kidney cortices of untreated db/db mice displayed increased ROCK activity compared with db/m mice. The fasudil-treated mice exhibited a significant reduction in ROCK activity, albuminuria, glomerular collagen IV accumulation, and urinary collagen IV excretion compared with untreated db/db mice. Interestingly, blood glucose was unaffected by fasudil administration. Treatment with simvastatin significantly attenuated RhoA activation in the kidney cortices of db/db mice and resulted in a significant reduction of albuminuria and mesangial matrix expansion.

CONCLUSIONS—Based on these results, we propose that RhoA/ROCK blockade constitutes a novel approach to the treatment of diabetic nephropathy. Our data also suggest a critical role for RhoA/ROCK activation in the pathogenesis of diabetic nephropathy.
Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum
Authors: Friedman Jacob E. , Kirwan John P. , Jing Ming , Presley Larraine , Catalano Patrick M.
Published: December 2007

OBJECTIVE—Women with gestational diabetes mellitus (GDM) demonstrate chronic and progressive insulin resistance and a markedly increased risk of converting to type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this insulin resistance are unknown.

RESEARCH DESIGN AND METHODS—We investigated the progression of insulin resistance in nine obese women with GDM during late pregnancy (30–36 weeks) and 1 year postpartum. Skeletal muscle biopsies were obtained at each visit, and insulin resistance was determined by the hyperinsulinemic-euglycemic clamp technique.

RESULTS—Insulin resistance was not significantly improved in GDM women (4.1 ± 0.4 vs. 5.8 ± 1.1 10−2 mg · kg FFM · min−1/μU · ml−1). Subjects did not experience significant weight loss postpartum. Body weight, fat mass, fasting glucose, and plasma tumor necrosis factor (TNF)-α remained higher 1 year postpartum than seen in previously studied normal glucose-tolerant women. Skeletal muscle TNF-α mRNA was elevated five- to sixfold in GDM women and remained higher 1 year postpartum. While levels of insulin receptor (IR), IR substrate (IRS)-1, and p85α improved postpartum, insulin-stimulated IR tyrosine phosphorylation and receptor tyrosine kinase activity did not significantly improve postpartum in GDM. The levels of 312Ser-IRS-1 also did not improve postpartum and correlated with TNF-α mRNA (r2 = 0.19, P < 0.03), consistent with a state of subclinical inflammation and chronic skeletal muscle insulin resistance.

CONCLUSIONS—These results suggest the mechanisms underlying chronic insulin resistance in GDM women may be driven by increased inflammation that impinges on the IR and IRS-1 signaling cascade in skeletal muscle. These findings have important implications for the health of GDM women during subsequent pregnancies and their risk for progression to type 2 diabetes.