bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model
Authors: Schurigt Uta , Sevenich Lisa , Vannier Corinne , Gajda Mieczyslaw , Schwinde Anne , Werner Fee , Stahl Andreas , von Elverfeldt Dominik , Becker Anne-Katrin , Bogyo Matthew , Peters Christoph , Reinheckel Thomas 
Published: August 2008

Abstract
Recent data suggest proteases of the papain-like cysteine cathepsin family as molecular targets for cancer therapy. Here, we report the treatment of polyoma middle T oncogene-induced breast cancers in mice with the cell-permeable broad-spectrum cysteine cathepsin inhibitor JPM-OEt. Up to 100 mg/kg inhibitor was intraperitoneally injected once per day in two trials on early and advanced cancers. In both trials, transient delays in tumour growth were observed. However, at the endpoint of both experiments no significant differences in tumour weights, histopathology and lung metastasis were found between the inhibitor and the control group. The invasive strand formation of collagen I-embedded tumour cell spheroids generated from primary tumours of inhibitor-treated mice in the early cancer trial could be inhibited in vitro by JPM-OEt; a result arguing against induction of resistance to the inhibitor. Measurement of cysteine cathepsin activities in tissue extracts after intraperitoneal injection of JPM-OEt revealed effective inhibition of cysteine cathepsins in pancreas, kidneys and liver, while activities in mammary cancers and in lungs were not significantly affected. We conclude that the pharmacokinetic properties of JPM-OEt, which result in poor bioavailability, may prohibit its use for stand-alone treatment of solid mammary cancers and their lung metastases.
Proteinases as hormones: targets and mechanisms for proteolytic signaling
Authors: Hansen Kristina K. , Oikonomopoulou Katerina , Baruch Amos , Ramachandran Rithwik , Beck Paul , Diamandis Eleftherios P. , Hollenberg Morley D. 
Published: August 2008

AbstractProteinases, such as kallikrein-related peptidases, trypsin and thrombin, can play hormone-like ‘messenger’ rolesin vivo. They can regulate cell signaling by cleaving and activating a novel family of G-protein-coupled proteinase-activated receptors (PARs 1–4) by unmasking a tethered receptor-triggering ligand. Short synthetic PAR-derived peptide sequences (PAR-APs) can selectively activate PARs 1, 2 and 4, causing physiological responsesin vitroandin vivo. Using the PAR-APs to activate the receptorsin vivo, it has been found that PARs, like hormone receptors, can affect the vascular, renal, respiratory, gastrointestinal, musculoskeletal and nervous systems (central and peripheral). PARs trigger responses ranging from vasodilatation to intestinal inflammation, increased cytokine production and increased nociception. These PAR-stimulated responses have been implicated in various disease states, including cancer, atherosclerosis, asthma, arthritis, colitis and Alzheimer's disease. In addition to targeting the PARs, proteinases can also cause hormone-like effects by other signaling mechanisms that may be as important as the activation of PARs. Thus, the PARs themselves, their activating serine proteinases and their signaling pathways can be considered as attractive targets for therapeutic drug development. Further, proteinases can be considered as physiologically relevant ‘hormone-like’ messengers that can convey signals locally or systemically either via PARs or by other mechanisms.
Expression of tissue and plasma kallikreins and kinin B1and B2receptors in lung cancer
Authors: Chee Jessica , Naran Anupam , Misso Neil L. , Thompson Philip J. , Bhoola Kanti D. 
Published: August 2008

AbstractTissue kallikrein (hK1) and plasma kallikrein (PK, hKB1) are serine proteases that produce biologically active kinin peptides from endogenous kininogen substrates. There is evidence linking the kallikreins and the mitogenic kinin peptides to carcinogenesis. The aim of this study was to investigate the expression of tissue prokallikrein (pro-hK1), plasma prekallikrein (PPK, pre-hKB1) and kinin B1and B2receptor proteins in different subtypes of lung cancer. Immunohistochemistry, using specific antibodies, was performed on archived normal lung sections and sections from adenocarcinomas, squamous cell carcinomas, large cell carcinomas, small cell carcinomas and carcinoid tumours of the lung. Immunoperoxidase labelling was visualised by brightfield microscopy and immunofluorescence labelling by confocal microscopy. Extensive cytoplasmic expression of pro-hK1 and PPK was observed, which was similar in small cell and non-small cell tumours. However, nuclear labelling for the kallikreins was absent or limited. The kinin B1and B2receptors were highly expressed in the cytoplasm of all tumour types and in the nuclei of non-small cell tumours. Further studies are required to assess the functional significance of the expression of hK1, PK and kinin receptors in lung tumours, and whether any of these proteins may be potential biomarkers for specific subtypes of lung carcinoma.
Hepatitis C virus (HCV) employs multiple strategies to subvert the host innate antiviral response
Authors: Bode Johannes G. , Brenndörfer Erwin D. , Häussinger Dieter 
Published: August 2008

Abstract
Hepatitis C virus (HCV) is a serious global health problem which accounts for approximately 40% of chronic liver diseases worldwide. HCV frequently establishes a persistent infection, although it is recognized and targeted by innate immunity as well as cellular and humoral immune mechanisms. This suggests that HCV has developed powerful strategies to escape elimination by innate and adaptive immunity. HCV-induced liver injury is thought to be mainly immune-mediated rather than due to direct cytopathic effects of the virus. Hence, therapeutic strategies should target those mechanisms favoring viral persistence since unspecific enhancement of host antiviral immunity may theoretically also promote liver injury. The present review summarizes our current understanding of how the hepatitis C virus interferes with the innate antiviral host-response to establish persistent infection.
Generation of synthetic RNA-based thermosensors
Authors: Waldminghaus Torsten , Kortmann Jens , Gesing Stefan , Narberhaus Franz 
Published: August 2008

Abstract
Structured RNAs with fundamental sensory and regulatory potential have been discovered in all kingdoms of life. Bacterial RNA thermometers are located in the 5′-untranslated region of certain heat shock and virulence genes. They regulate translation by masking the Shine-Dalgarno sequence in a temperature-dependent manner. To engineer RNA-based thermosensors, we used a combination of computer-based rational design and in vivo screening. After only two rounds of selection, several RNA thermometers that are at least as efficient as natural thermometers were obtained. Structure probing experiments revealed temperature-dependent conformational changes in these translational control elements. Our study demonstrates that temperature-controlled RNA elements can be designed by a simple combined computational and experimental approach.
Effects of the Cdc2-like kinase-family and DNA topoisomerase I on the alternative splicing of eNOS in TNF-α-stimulated human endothelial cells
Authors: Eisenreich Andreas , Boltzen Ulrike , Poller Wolfgang , Schultheiss Heinz-Peter , Rauch Ursula 
Published: August 2008

AbstractNitric oxide (NO) is synthesized by endothelial nitric oxide synthase (eNOS) and plays an important role in vascular homeostasis and cardiovascular diseases. It has recently been shown that increased expression of alternatively spliced eNOS isoforms eNOS 13A, B and C and heterodimerization with ‘full-length’ eNOS is associated with a decreased eNOS activity. The regulatory pathways enabling this phenomenon are completely unknown. This study examined the effect of Cdc2-like kinases and DNA topoisomerase I on eNOS splicing in TNF-α-induced human umbilical vein endothelial cells (HUVECs). We found that inhibition of DNA topoisomerase I, but not Cdc2-like kinases, prevents the TNF-α-induced increase in eNOS isoform expression and NO reduction in HUVEC. Moreover, we show that the inhibition of DNA topoisomerase I or the Cdc2-like kinases differently modulates the phosphorylation of the serine/arginine-rich proteins SRp75 and SRp55. Our results demonstrate, for the first time, that DNA topoisomerase I but not Cdc2-like kinases serves as an important regulator of the differential eNOS isoform expression in endothelial cells, thereby modulating the TNF-α-induced eNOS activity switch.
Cytotoxic and peptidase inhibitory activities of selected non-hepatotoxic cyclic peptides from cyanobacteria
Authors: Bubik Anja , Sedmak Bojan , Novinec Marko , Lenarčič Brigita , Lah Tamara T. 
Published: August 2008

Abstract
Toxic cyanobacterial blooms are a rich source of metabolites having a variety of biological activities. Two main groups of cyclic peptides, depsipeptides and ureido linkage-containing peptides, reportedly inhibit serine peptidases. We characterised their inhibitory properties against selected peptidases and investigated their influence on cell viability. The depsipeptide planktopeptin BL1125 is a strong linear competitive tight-binding inhibitor of leukocyte (K
i=2.9 nm) and pancreatic (K
i=7.2 nm) elastase and also of chymotrypsin (K
i=6.1 nm). Anabaenopeptins B and F show no inhibition against chymotrypsin, but inhibit both elastases. The tested cyclic peptides do not inhibit trypsin, urokinase, kallikrein 1 or cysteine peptidases. All three tested cyanopeptides show no short-term cytotoxicity in concentrations of up to 10 μm, but impair the metabolic activity of normal human astrocytes after prolonged exposure (48–96 h), whereas glioblastoma cells, tumour cells of the same type, are resistant. Strong inhibition and relative selectivity of the tested cyanopeptides suggests that they are potential candidates for application in inflammatory diseases and possibly some types of cancers.
Survey and phytochemical analysis of seagrasses in the Gulf of Mannar, southeast coast of India
Authors: Athiperumalsami Thirumalai , Kumar Venkataraman , Jesudass L. Louis 
Published: August 2008

Abstract
Of the six genera of seagrasses recorded in India, four were present throughout a 1-year study period at a station off Hare Island, Tuticorin (8°45′ N, 78°12′ E), in the Gulf of Mannar region. Phytochemical analysis of these seagrass extracts revealed the presence of pharmaceutically potent secondary metabolites and appreciable quantities of primary and some secondary metabolites.
Virtual Cultural Heritage – eine immersive, multimediale Anwendung am Beispiel des Klosters Georgenthal (Virtual Cultural Heritage – an Immersive Multimedia Application Showcase of the Monastery Georgenthal)
Authors: Böse Ralf , Spierling Ulrike , Struck Hans-Georg 
Published: August 2008

Zusammenfassung
In diesem Beitrag werden die Konzeption und die prototypische Umsetzung eines stereoskopischen Kurzfilms in Verbindung mit einem 3D Soundsystem auf Basis der Wellenfeldsynthese vorgestellt. Die Installation ist Teil einer Museumskonzeption für den geplanten barrierefreien Erlebnispark, Klostervision' in Georgenthal, Thüringen. Sie ist weltweit die erste Installation in diesem Anwendungskontext. Besonders wird auf das inhaltliche Konzept eingegangen, das mit Hilfe einer packenden Story die Immersion des Mediums für die Wissensvermittlung ausnutzt, und deren Wirkung erläutert. Weiterhin wird die Umsetzung beschrieben, deren Herausforderungen in stereoskopischen Realaufnahmen, computer-grafischen Szenen, 3D- Compositing und einer Integration in das räumliche Audiosystem IOSONO bestanden.
The qSD12 Locus Controls Offspring Tissue-Imposed Seed Dormancy in Rice
Authors: Gu Xing-You , Turnipseed E Brent , Foley Michael E 
Published: August 2008

Abstract
Seed component structures were grouped into maternal and offspring (embryo and endosperm) tissues to characterize a dormancy quantitative trait locus (QTL) for tissue-specific function using a marker-assisted genetic approach. The approach was devised to test if genotypic/allelic frequencies of a marker tightly linked to the QTL deviate from Mendelian expectations in germinated and nongerminated subpopulations derived from a segregation population of partially after-ripened seeds and was applied to the dormancy QTL qSD12 and qSD7-1 in a nearly isogenic background of rice. Experimental results unambiguously demonstrated that qSD12 functions in the offspring tissue(s) and suggested that qSD7-1 may control dormancy through the maternal tissues. These experiments also provide the first solid evidence that an offspring tissue-imposed dormancy gene contributes to the segregation distortion in a mapping population developed from partially after-ripened seeds and, in part, to the germination heterogeneity of seeds from hybrid plants. Offspring and maternal tissue-imposed dormancy genes express in very early and late stages of the life cycle, respectively, and interact to provide the species with complementary adaptation strategies. The qSD12 locus was narrowed to the region of ∼600 kbp on a high-resolution map to facilitate cloning and marker-assisted selection of the major dormancy gene.
A kinetic model for the relative contribution of waterborne and dietary cadmium and zinc in the common carp (Cyprinus carpio)
Authors: Van Campenhout Karen , Bervoets Lieven , Redeker Erik Steen , Blust Ronny 
Published: August 2008

AbstractIn this work, the uptake and whole-body accumulation of Cd and Zn by the common carp from water, diet, and a combination of both was studied using the radioactive tracers 109Cd and 65Zn. A three-compartment pharmacokinetic model was constructed and revealed metal- and exposure route–dependent accumulation profiles. Under the tested exposure conditions in water (0.1 μM Cd and 1 μM Zn), only 0.1 and 0.07%, respectively, of the total Cd and Zn load that passed the branchial surfaces was accumulated by the carp. In contrast, the carp accumulated 20 and 29% of the total ingested Cd and Zn load (mean concentrations in food of newly accumulated metals were 2.24 ± 0.29 and 19.91 ± 2.89 nmol/g wet weight, respectively). However, the contribution of the waterborne metals to the whole-body metal accumulation was higher than the metal uptake from food. The constructed model was used to simulate the effect of variable assimilation efficiency (AE) values on the relative importance of dietary Cd and Zn exposure to the overall metal accumulation in common carp. This simulation was performed under a realistic exposure scenario and with Cd and Zn AE values ranging from 5 to 95%. Dissolved Zn levels were higher and Cd levels lower compared to the laboratory experiments. Levels in the midge larvae were much higher. The results show that under these conditions, even at the lowest Cd and Zn AEs, almost 40% of the total body Cd and Zn concentrations originated from dietary Cd and Zn exposure. Taking into account the Cd and Zn AE of the laboratory experiments, respectively, 31 and 55%, more than 85% of the total body Cd and Zn was taken up from the food.
Substance or space? The relative importance of substance properties and environmental characteristics in modeling the fate of chemicals in Europe
Authors: Hollander Anne , Pistocchi Alberto , Huijbregts Mark A. J. , Ragas Ad M. J. , Van De Meent Dik 
Published: August 2008

AbstractThe relative influence of substance properties and of environmental characteristics on the variation in the environmental fate of chemicals was studied systematically and comprehensively. This was done by modeling environmental concentrations for 200 sets of substance properties, representative of organic chemicals used, and 137 sets of environmental characteristics, representative of regions in Europe of 250 × 250 km. Since it was expected that the model scale has an influence on the predicted concentration variations, the calculations were repeated for regions with a 100 × 100 km and 50 × 50 km area. Stepwise multiple regression analysis was performed to determine the contribution of each of the individual input parameters on the total concentration variation. Depending on the scenario, the range in predicted environmental concentrations spreads from two up to nine orders of magnitude. In accord with earlier studies, variation in the fate of chemicals in the environment appeared to depend mainly on substance-specific partition coefficients and degradation rates. For the estimation of soil and water concentrations with direct emissions to these compartments, however, the influence of spatial variation in environmental characteristics can mount up to two orders of magnitude, a range that can be significant to account for in certain model applications. Concentration differences in water and soil are predicted to be larger if a smaller region is applied in the model calculations, and the relative influence of environmental characteristics on the total variation increases on a more detailed spatial scale. It is argued that the influence of environmental characteristics as predictors of exposure concentrations of chemicals deserves better attention in comparative risk assessment with conventional nonspatial multimedia box models.
Chiral Bis(N‐arylamino)phosphine‐oxazolines: Synthesis and Application in Asymmetric Catalysis
Authors: Schönleber Marc , Hilgraf Robert , Pfaltz Andreas 
Published: August 2008

AbstractN‐Arylation or N‐alkylation of chiral 1,2‐diamines followed by ring closure with phosphorus trichloride (PCl3) and subsequent coupling with an oxazoline alcohol resulted in a new class of N,P ligands. The corresponding iridium tetrakis[3,5‐bis(trifluormethyl)phenyl]borate (BArF) complexes were found to be efficient catalysts for the enantioselective hydrogenation of unfunctionalized olefins and α,β‐unsaturated carboxylic esters.
Palladium‐Iminodiacetic Acid Immobilized on pH‐Responsive Polymeric Microspheres: Efficient Quasi‐Homogeneous Catalyst for Suzuki and Heck Reactions in Aqueous Solution
Authors: Zhang Jianzheng , Zhang Wangqing , Wang Yao , Zhang Minchao 
Published: August 2008

AbstractThe pH‐responsive core‐shell microspheres of poly(styrene‐co‐methylacrylic acid) (PS‐co‐PMAA) containing a polystyrene (PS) core and a poly(methylacrylic acid) (PMAA) shell are synthesized by one‐stage soap‐free copolymerization and the catalyst system palladium‐iminodiacetic acid (IDA‐Pd) is immobilized on the outer shell‐layer of the core‐shell microspheres to form the quasi‐homogeneous and easily accessible catalyst PS‐co‐PMAA‐IDA‐Pd. This quasi‐homogeneous PS‐co‐PMAA‐IDA‐Pd catalyst is highly dispersed in the reaction medium just like a homogeneous one and can be separated like a heterogeneous catalyst by adjusting the pH of the reaction medium. Suzuki reactions employing the quasi‐homogeneous PS‐co‐PMAA‐IDA‐Pd catalyst are efficiently performed in water as the sole solvent under mild conditions such as room temperature. The PS‐co‐PMAA‐IDA‐Pd catalyst is also used in Heck reactions of a wide range of aryl halides with styrene and proves to be efficient in aqueous solution. The PS‐co‐PMAA‐IDA‐Pd catalyst has a low leaching loss and can be reused at least 4 times without loss of activity.
Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease associated pulmonary hypertension
Authors: van Beers Eduard J. , Nur Erfan , Schaefer‐Prokop Cornelia M. , Mac Gillavry Melvin R. , van Esser Joost W.J. , Brandjes Dees P.M. , Kappers‐Klunne Maria C. , Duits Ashley J. , Muskiet Frits A.J. , Schnog John‐John B. , Biemond Bart J. 
Published: August 2008

AbstractPulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high‐resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N‐terminal brain natriuretic peptide (NT‐proBNP) and brain natriuretic peptide (BNP) in patients with SCD‐related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of ≥2.5 m/sec). All patients were systematically evaluated by the aforementioned diagnostic tests comparing patients with and without PHT. The prevalence of PHT was 41% in HbSS/HbSβ0–thalassemia patients and 13% in HbSC/HbSβ+‐thalassemia patients. No statistically significant differences were detected in ECG, chest radiography, HRCT, and pulmonary function testing between patients with and without PHT. The degree of anemia and renal dysfunction, but not the presence of PHT, were the most important determinants of plasma (NT‐pro)BNP levels. The performed imaging and functional studies do not seem to be of value in identifying etiological conditions (such as airflow obstruction or parenchymal lung disease) nor do they offer clues to the presence of mild PHT in SCD. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Delayed‐onset HIT caused by low‐molecular‐weight heparin manifesting during fondaparinux prophylaxis
Authors: Alsaleh Khalid A. , Al‐Nasser Sami M. A. , Bates Shannon M. , Patel Ameen , Warkentin Theodore E. , Arnold Donald M. 
Published: August 2008

AbstractHeparin‐induced thrombocytopenia (HIT) is a prothrombotic condition caused by platelet‐activating antibodies that react with platelet factor 4 (PF4)/heparin complexes. Delayed‐onset HIT occurs after heparin is stopped. Fondaparinux, a synthetic pentasaccharide, is thought to be a safe alternative anticoagulant in HIT. We describe a patient with delayed‐onset HIT triggered by low‐molecular‐weight heparin (LMWH) which occurred during fondaparinux prophylaxis and which was complicated by microangiopathic hemolytic anemia. Patient serum contained high‐titer anti‐PF4/heparin antibodies demonstrating heparin‐dependent platelet activation with serial dilutions. Confirmed delayed‐onset HIT with LMWH has not been previously reported. Low dose fondaparinux does not necessarily prevent thrombotic complications of HIT. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Biosorption of basic dyes onto Azolla filiculoides: equilibrium and kinetic modeling
Authors: Padmesh T. V. N. , Vijayaraghavan K. , Anand K. , Velan M. 
Published: August 2008

AbstractThe biosorption of basic dyes, rhodamine B (RMB) and methylene blue (MB), using Azolla filiculoides was investigated in a batch reactor and in a fixed‐bed column. Biosorption isotherms revealed that pH 5 was the optimum condition for maximum biosorption of both basic dyes. Sorption isotherm data were fitted with Langmuir, Freundlich, Redlich–Peterson and Sips models. A maximum uptake of 166.7 and 91.8 mg/g was observed for MB and RMB, respectively, according to the Langmuir model. It was observed from the kinetic data that the biosorption process using A. filiculoides followed pseudo‐second order kinetics. The ability of A. filiculoides to biosorb MB in a packed column was investigated, as well. Experiments conducted at different bed heights (15–25 cm) revealed that decrease in bed height resulted in inferior biosorption performance. At 25 cm, the A. filiculoides bed was capable of providing breakthrough at 76.2 h, with column uptake and removal efficiency of 80.2 mg/g and 84.9%, respectively. The Thomas model was successfully used to analyze the experimental data and the model parameters were evaluated. Copyright © 2008 Curtin University of Technology and John Wiley & Sons, Ltd.