bluuebunny/crossref_metadata_2025_split huggingface dataset:
A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study
Authors: Holubarsch Christian J. F. , Rohrbach Martin , Karrasch Matthias , Boehm Erich , Polonski Lech , Ponikowski Piotr , Rhein Siegfried 
Published: July 2007

Etomoxir is an inhibitor of mitochondrial CPT1 (carnitine palmitoyltransferase 1) and thereby switches energy metabolism from fatty acids to glucose oxidation. Such a metabolic change may be beneficial in CHF (congestive heart failure). The ERGO (etomoxir for the recovery of glucose oxidation) study was designed in which etomoxir was tested at a dose of 80 and 40 mg compared with placebo for a period of 6 months in patients with CHF. As the principle measure of efficacy, a maximal exercise tolerance test and a submaximal 6-min corridor walk test were used. Secondary end points were echocardiographical dimensions and quality-of-life assessment scores. A total of 350 patients were planned to be screened, with the expectation that end point data would be available from approx. 260 patients. However, the study had to be stopped prematurely, because unacceptably high liver transaminase levels were detected in four patients taking etomoxir. At the termination of the study, 121 patients were randomized to placebo, 118 to 40 mg of etomoxir and 108 to 80 mg of etomoxir. At that time, 21 patients in the placebo group, 16 in the 40 mg of etomoxir group and 14 patients in the 80 mg of etomoxir group had completed the study. The mean increases in exercise time were 3.3, 10.2 and 19.4 s for the placebo, 40 mg of etomoxir and 80 mg of etomoxir groups respectively (P value was not significant). No changes were obvious in the 6-min corridor walk test or in echocardiographical parameters from baseline. The number of patients that completed the study was too small to demonstrate significant effects on exercise time, although there was a tendency towards an increase in exercise time. Therefore, before rejecting the hypothesis that inhibition of fatty acid oxidation might be beneficial in CHF, similar studies have to be performed using different inhibitors of fatty acid oxidation targeting CPT1 and other enzymes in this metabolic pathway.
Different effects of ribosome biogenesis inhibition on cell proliferation in retinoblastoma protein‐ and p53‐deficient and proficient human osteosarcoma cell lines
Authors: Montanaro L. , Mazzini G. , Barbieri S. , Vici M. , Nardi‐Pantoli A. , Govoni M. , Donati G. , Treré D. , Derenzini M. 
Published: July 2007

Abstract.  Objectives: To evaluate the effects of rRNA synthesis inhibition on cell cycle progression and cell population growth according to the RB and p53 status. Material and methods: RB‐ and p53‐proficient U2OS cells and the RB‐ and p53‐deficient SAOS‐2 cells were used, rRNA transcription hindered by actinomycin D, and cell cycle analysed by flow cytometry. Results: One hour of actinomycin D treatment induced in U2OS cells a block at the cell cycle checkpoints G1‐S and G2‐M, which was removed only after rRNA synthesis was resumed. rRNA synthesis inhibition did not influence cell cycle progression in SAOS‐2 cells. No effect on cell cycle progression after actinomycin D‐induced rRNA inhibition was also found in U2OS cells silenced for RB and p53 expression. A mild perturbation of cell cycle progression was observed in U2OS cells silenced for the expression of either RB or p53 alone. We also treated U2OS and SAOS‐2 cells with actinomycin D for 1 h/day for 5 days. This treatment lightly reduced growth rate of the U2OS cell population, whereas cell population growth of SAOS‐2 cells was completely inhibited. A marked reduction of ribosome content occurred in SAOS‐2 cells after the long‐term actinomycin D treatment, whereas no modification was observed in U2OS cells. Conclusions: These results demonstrate that inhibition of ribosome biogenesis does not hinder cell cycle progression in RB‐ and p53‐deficient cells. A daily‐repeated transitory inhibition of ribosome biogenesis leads to a progressive reduction of ribosome content with the consequent extinction of cancer cell population lacking RB and p53.
Driving forces shaping phytoplankton assemblages in two subtropical plateau lakes with contrasting trophic status
Authors: ZHANG XIA , XIE PING , CHEN FEIZHOU , LI SIXIN , QIN JIANHUI 
Published: July 2007

Summary1. We studied driving forces shaping phytoplankton assemblages in two subtropical plateau lakes with contrasting trophic status, the oligotrophic deep Lake Fuxian and the eutrophic shallow Lake Xingyun.2. Phytoplankton samples were taken monthly for a year and phytoplankton species were sorted into the main taxonomic groups and associations proposed by Reynolds. A canonical correspondence analysis (CCA) was used to test the occurrence of these classification schemes and to determine their discriminatory power.3. The results suggest that the major driving forces in Lake Fuxian were physical variables, and particularly the underwater light climate, whereas, nutrients were the important driving force in Lake Xingyun.4. Top–down control through zooplankton grazing in Lake Fuxian was hardly ever a significant determinant itself, because of the scarcity of zooplankton and their low grazing efficiency of predation while a dominance of inedible cyanobacteria throughout the year rendered top–down controls ineffective failing in Lake Xingyun. Hence phytoplankton communities in both lakes appear to be regulated primarily by bottom–up controls.
Interleukin‐21 differentially affects human natural killer cell subsets
Authors: Wendt Katy , Wilk Esther , Buyny Sabine , Schmidt Reinhold Ernst , Jacobs Roland 
Published: July 2007

SummaryInterleukin‐21 (IL‐21) is a cytokine with pleiotropic effects on various cell types including dendritic cells, B cells, T cells and natural killer (NK) cells. To evaluate if IL‐21 affects human NK cell subpopulations in a similar fashion, functional studies were performed on CD56dim and CD56bright NK cells, both bearing IL‐21 receptors at identical densities. Stimulation with IL‐21 strongly induced proliferation of CD56bright NK cells and cytotoxicity against K562 target cells was preferentially augmented in CD56dim NK cells. In contrast, stimulation with IL‐2 and IL‐21 alone or in combination failed to induce interferon‐γ and tumour necrosis factor‐α production in the two NK cell subsets. Intracellular analysis of signal transducer and activator of transcription (STAT) proteins revealed that IL‐21 by itself induces phosphorylation of STAT1 and STAT3 in CD56dim NK cells, and to an even higher degree in CD56bright NK cells. In this CD56bright NK cell population alone, IL‐2 weakly phosphorylated STAT1 and STAT3, which was further increased when cells were treated with the combination of both cytokines. In contrast, STAT5 was strongly phosphorylated only in CD56bright NK cells by low‐dose IL‐2, while IL‐21 did not affect STAT5 at all. In summary, we present data indicating that the NK‐cell‐directed cytokines IL‐2 and IL‐21 not only affect functions in NK cell subpopulations differently but can also act additively.
FtsH protease is required for induction of inorganic carbon acquisition complexes in Synechocystis sp. PCC 6803
Authors: Zhang Pengpeng , Sicora Cosmin I. , Vorontsova Natalia , Allahverdiyeva Yagut , Battchikova Natalia , Nixon Peter J. , Aro Eva‐Mari 
Published: July 2007

SummaryCyanobacteria possess a complex CO2‐concentrating mechanism (CCM), which is induced by low inorganic carbon conditions. To investigate the involvement of proteases in the processes of induction and degradation of the CCM complexes, we studied the FtsH2 (ΔSlr0228) and Deg‐G (ΔSlr1204/ΔSll1679/ΔSll1427) protease mutants of Synechocystis sp. PCC 6803. WT and protease mutant cells were grown under high CO2 and then shifted to low CO2, followed by a proteome analysis of the membrane protein complexes. Interestingly, in the FtsH2 protease mutant, inducible CCM complexes were not detected upon shift to low CO2, whereas the Deg‐G mutant behaved like WT. Also the transcripts of the inducible CCM genes and their regulator ndhR failed to accumulate upon shift of FtsH2 mutant cells from high to low CO2, indicating that the regulation by the FtsH2 protease is upstream of NdhR. Moreover, functional photosynthesis was shown a prerequisite for induction of CCM in WT at low CO2, possibly via generation of oxidative stress, which was shown here to enhance the expression of inducible CCM genes even at high CO2 conditions. Once synthesized, the CCM complexes were not subject to proteolytic degradation, even when dispensable upon a shift of cells to high CO2.
Lysis of a Broad Range of Epithelial Tumour Cells by Human γδ T Cells: Involvement of NKG2D ligands and T‐cell Receptor‐ versus NKG2D‐dependent Recognition
Authors: Wrobel P. , Shojaei H. , Schittek B. , Gieseler F. , Wollenberg B. , Kalthoff H. , Kabelitz D. , Wesch D. 
Published: July 2007

AbstractHuman γδ T cells expressing a Vγ9Vδ2 T‐cell receptor (TCR) kill various tumour cells including autologous tumours. In addition to TCR‐dependent recognition, activation of NKG2D‐positive γδ T cells by tumour cell‐expressed NKG2D ligands can also trigger cytotoxic effector function. In this study, we investigated the involvement of TCR versus NKG2D in tumour cell recognition as a prerequisite to identify tumour types suitable for γδ T‐cell‐based immunotherapy. We have characterized epithelial tumour cells of different origin with respect to cell surface expression of the known NKG2D ligands MHC class I‐chain‐related antigens (MIC) A/B and UL16‐binding proteins (ULBP), and susceptibility to γδ T‐cell killing. Most tumour cells expressed comparable levels of MICA and MICB as well as ULBP with the exception of ULBP‐1 which was absent or only weakly expressed. Most epithelial tumours were susceptible to allogeneic γδ T‐cell lysis and in the case of an established ovarian carcinoma to autologous γδ T‐cell killing. Lysis of resistant cells was enhanced by pre‐treatment of tumour cells with aminobisphosphonates or pre‐activation of γδ T cells with phosphoantigens. A potential involvement of TCR and/or NKG2D was investigated by antibody blockade. These experiments revealed three patterns of inhibition, i.e. preferential inhibition by anti‐TCR antibody, preferential inhibition by anti‐NKG2D antibody, or additive blockade by anti‐TCR plus anti‐NKG2D antibodies. Our results indicate for the first time that the NKG2D pathway is involved in the lysis of different melanomas, pancreatic adenocarcinomas, squameous cell carcinomas of the head and neck, and lung carcinoma.
NK1.1 Cells Downregulate Murine Endotoxin‐Induced Uveitis Following Intraocular Administration of Interleukin‐12
Authors: Figueiredo F. , Commodaro A. G. , De Camargo M. M. , Rizzo L. V. , Belfort R. 
Published: July 2007

AbstractTo evaluate the role of IFN‐γ (interferon gamma) in IL‐12‐ (interleukin‐12)‐induced inhibition of the inflammatory response in the eye during endotoxin‐induced uveitis (EIU). C57BL/6 wild type mice and IFN‐γ‐deficient (GKO) mice were injected with 250 μg of Salmonella typhymurium endotoxin as a model for EIU. Animals were then injected intraocularly with 100 ng of rIL‐12 or the equivalent volume of Phosphate‐buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase‐polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN‐γ was performed using the R4‐6A2 antibody. C57BL/6 mice treated with rIL‐12 intraocularly were protected from the development of EIU. Neutralization of IFN‐γ with a monoclonal antibody abrogated such protection. The IL‐12 protective effects were lost in NK1.1‐depleted mice. Intraocular IL‐12 decreased the expression of keratinocyte‐derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP‐2) gene. The protective effect of IL‐12 during EIU occurs through production of IFN‐γ by NK1.1+ cells. IL‐12‐induced higher levels of IFN‐γ are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.
Confusion assessment method for the intensive care unit (CAM‐ICU): translation, retranslation and validation into Swedish intensive care settings
Authors: Larsson C. , Axell A. Granberg , Ersson A. 
Published: July 2007

Background:  Becoming critical ill or severely injured leads to a process of worry, anxiety and pain. Patients in intensive care sometimes have strange and frightening experiences and may show symptoms of acute confusion or delirium. CAM‐ICU, the confusion assessment method for the intensive care unit, was based on the DSM IV, the Diagnostic and Statistic Manual of Mental Disorders IV, and today, healthcare professionals and researchers are increasingly accepting this concept of diagnosing ICU delirium. In Sweden, there is no commonly used, single instrument or method to test the development of ICU delirium. The aim of this study was to translate, retranslate and validate CAM‐ICU for use in Swedish ICU settings.Methods:  The translation of the instrument was done according to the guidelines suggested by The Translation and Cultural Adaptation group which includes preparation, forward translation/reconciliation, back translation, back translation review, harmonization, cognitive debriefing and validation. In the validation process, the applicability of the Swedish version of the instruments was tested in a Swedish intensive care unit.Results:  Fourteen adult patients were included in the study, 40 paired tests were carried out, and 80 CAM‐ICU instruments were completed. The participating patients were given CAM‐ICU ratings using independent paired evaluations by two nurses, specialized in intensive care, at least twice during the patients’ stay in the ICU. Interrater reliability was calculated using kappa statistics. In the 40 paired observations, interrater reliability was ‘very good’ (kappa statistics > 0.81). In our material, we recognized a delirium rate of 48%, which is in accordance with previous studies.Conclusion:  The translation of the instrument CAM‐ICU showed good correlation with the original version and could therefore be applicable in a Swedish ICU setting. In the 40 paired observations, interrater reliability was very good. Although there are limitations in using CAM‐ICU, previous studies reveal a need for a homogeneous screening instrument making it possible to detect and determine ICU delirium; and from this basis are able to implement and make the necessary decisions required in medical and nursing care practice preventing ICU delirium.
Enzymatic oxidation of NADP+ to its 4‐oxo derivative is a side‐reaction displayed only by the adrenodoxin reductase type of ferredoxin‐NADP+ reductases
Authors: de Rosa Matteo , Pennati Andrea , Pandini Vittorio , Monzani Enrico , Zanetti Giuliana , Aliverti Alessandro 
Published: July 2007

We have previously shown that Mycobacterium tuberculosis FprA, an NADPH‐ferredoxin reductase homologous to mammalian adrenodoxin reductase, promotes the oxidation of NADP+ to its 4‐oxo derivative 3‐carboxamide‐4‐pyridone adenine dinucleotide phosphate [Bossi RT, Aliverti A, Raimondi D, Fischer F, Zanetti G, Ferrari D, Tahallah N, Maier CS, Heck AJ, Rizzi M et al. (2002) Biochemistry41, 8807–8818]. Here, we provide a detailed study of this unusual enzyme reaction, showing that it occurs at a very slow rate (0.14 h−1), requires the participation of the enzyme‐bound FAD, and is regiospecific in affecting only the C4 of the NADP nicotinamide ring. By protein engineering, we excluded the involvement in catalysis of residues Glu214 and His57, previously suggested to be implicated on the basis of their localization in the three‐dimensional structure of the enzyme. Our results substantiate a catalytic mechanism for 3‐carboxamide‐4‐pyridone adenine dinucleotide phosphate formation in which the initial and rate‐determining step is the nucleophilic attack of the nicotinamide moiety by an active site water molecule. Whereas plant‐type ferredoxin reductases were unable to oxidize NADP+, the mammalian adrenodoxin reductase also catalyzed this unusual reaction. Thus, the 3‐carboxamide‐4‐pyridone adenine dinucleotide phosphate formation reaction seems to be a peculiar feature of the mitochondrial type of ferredoxin reductases, possibly reflecting conserved properties of their active sites. Furthermore, we showed that 3‐carboxamide‐4‐pyridone adenine dinucleotide phosphate is good ligand and a competitive inhibitor of various dehydrogenases, making this nucleotide analog a useful tool for the characterization of the cosubstrate‐binding site of NADPH‐dependent enzymes.
The local supermassive black hole mass density: corrections for dependencies on the Hubble constant
Authors: Graham Alister W. , Driver Simon P. 
Published: July 2007

Abstract
We have investigated past measurements of the local supermassive black hole mass density, correcting for hitherto unknown dependencies on the Hubble constant, which, in some cases, had led to an underestimation of the mass density by factors of ∼2. Correcting for this, we note that the majority of (but not all) past studies yield a local supermassive black hole mass density that is consistent with the range 4.4–5.9 × 105f(H0) M⊙ Mpc−3 (when using H0= 70 km s−1 Mpc−1). In addition, we address a number of ways in which these past estimates can be further developed. In particular, we tabulate realistic bulge-to-total flux ratios which can be used to estimate the luminosity of bulges and subsequently their central black hole masses.
Moonlets wandering on a leash-ring
Authors: Winter O. C. , Mourão D. C. , Giuliatti Winter S. M. , Spahn F. , Da Cruz C. 
Published: July 2007

Abstract
Since the Voyager flybys, embedded moonlets have been proposed to explain some of the surprising structures observed in Saturn's narrow F ring. Experiments conducted with the Cassini spacecraft support this suggestion. Images of the F ring show bright compact spots, and seven occultations of stars by the F ring, monitored by ultraviolet and infrared experiments, revealed nine events of high optical depth. These results point to a large number of such objects, but it is not clear whether they are solid moonlets or rather loose particle aggregates. Subsequent images suggested an irregular motion of these objects so that a determination of their orbits consistent with the F ring failed. Some of these features seem to cross the whole ring. Here we show that these observations are explained by chaos in the F ring driven mainly by the ‘shepherd’ moons Prometheus and Pandora. It is characterized by a rather short Lyapunov time of about a few hundred orbital periods. Despite this chaotic diffusion, more than 93 per cent of the F-ring bodies remain confined within the F ring because of the shepherding, but also because of a weak radial mobility contrasted by an effective longitudinal diffusion. This chaotic stirring of all bodies involved prevents the formation of ‘propellers’ typical of moonlets, but their frequent ring crossings explain the multiple radial ‘streaks’ seen in the F ring. The related ‘thermal’ motion causes more frequent collisions between all bodies which steadily replenish F-ring dust and allow for ongoing fragmentation and re-accretion processes (ring recycling).
Do mergers spin-up dark matter haloes?
Authors: D'Onghia Elena , Navarro Julio F. 
Published: July 2007

Abstract
We use a large cosmological N-body simulation to study the origin of possible correlations between the merging history and spin of cold dark matter haloes. In particular, we examine claims that remnants of major mergers tend to have higher-than-average spins, and find that the effect is driven largely by unrelaxed systems: equilibrium dark matter haloes show no significant correlation between spin and merging history. Out-of-equilibrium haloes have, on average, higher spin than relaxed systems, suggesting that the virialization process leads to a net decrease in the value of the spin parameter. We find that this decrease is due to the internal redistribution of mass and angular momentum that occurs during virialization. This process is especially efficient during major mergers, when high angular momentum material is pushed beyond the virial radius of the remnant. Because such redistribution likely affects the angular momentum of baryons and dark matter unevenly, our findings question the common practice of identifying the specific angular momentum content of a halo with that of its embedded luminous component. Further work is needed to elucidate the true relation between the angular momentum content of baryons and dark matter in galaxy systems assembled hierarchically.
The Western Accretionary Margin of the East European Craton: an overview
Authors: Pharaoh T. C. , Winchester J. A. , Verniers J. , Lassen A. , Seghedi A. 
Published: July 2007

Abstract
Multidisciplinary investigations of the western margin of the East European Craton (EEC) by EUROPROBE projects since 1992 have confirmed that the Trans-European Suture Zone (TESZ) is the most fundamental lithospheric boundary in Europe, extending 2000 km from the North Sea to the Black Sea-Crimean region. The crust of the EEC is thicker and denser than that of Phanerozoic-accreted Europe, and the base of the lithospheric mantle significantly deeper. These characteristics persist throughout the length of the TESZ, despite the variation in age of the accreted crust along strike. Geological studies of key deep borehole cores and the limited outcrop data confirm that the crust of Phanerozoic-accreted Central Europe comprises a number of terranes, each thought to be derived from Gondwana during several episodes of rifting, ocean formation, ocean destruction and sequential accretion to the EEC throughout Palaeozoic time. There is still much discussion about the identity, provenance and history of these orogenic terranes. The process of accretion led to the formation of terrane-bounding orogenic sutures, which may be marked in outcrop by ophiolitic and eclogitic relics. Recognition of concealed sutures is obviously more difficult, and relies on a variety of geophysical techniques, used in an integrated way by multidisciplinary teams; the evidence from deep seismic reflection and refraction surveys, teleseismic tomography, magnetotelluric experiments and from geophysical potential-field modelling is crucial for such studies. Since the European Geotraverse, much has been learnt about the geometry of the Thor, Iapetus, Rheic, Saxo-Thuringian and Moldanubian oceanic sutures, through the crust and sometimes into the mantle. This has led to a much better understanding of the 3D crustal structure of the Western Accretionary Margin of the EEC, and the lithospheric processes that have shaped it. From this, the influence of tectonic heterogeneities within the orogenic crust on the development of post-orogenic structures and basins can be much better constrained.