bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUC1 Expression Is Repressed by Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y
Authors: Brayman Melissa Jo , Dharmaraj Neeraja , Lagow Errin , Carson Daniel D. 
Published: August 2007

AbstractMucin 1 (MUC1) is a transmembrane glycoprotein that modulates the interaction between the embryo and the uterine epithelial cell surface. MUC1 also is a tumor marker and has been implicated in the protection of cancer cells from immune cell attack as well as in cell signaling in some tumors. We and others have shown that MUC1 expression is activated by progesterone (P), TNF-α, and interferon-γ (IFN-γ). Here we demonstrate that MUC1 expression is down-regulated by overexpression of members of the protein inhibitor of activated signal transducer and activator of transcription (PIAS) family, PIAS1, PIAS3, PIASxα, PIASxβ, and PIASy, in human uterine epithelial cell lines HES and HEC-1A and in a breast cancer cell line, T47D. Treatments with P, TNF-α, and IFN-γ were unable to overcome the repression by PIASy. PIASy repression of basal, P-, and TNF-α-stimulated MUC1 promoter activity was not dependent on the PIASy sumoylation domain. In contrast, PIASy suppression of IFN-γ-activated MUC1 promoter activity was dependent on the PIASy sumoylation domain. PIASy and P receptor B were localized to the nucleus upon P treatment, and small interfering RNA knockdown of PIASy resulted in an increase in P-mediated stimulation of MUC1 protein expression. Overexpression of PIASy did not affect P receptor B binding to the MUC1 promoter but surprisingly led to a loss of nuclear receptor corepressor (NCoR), which was recruited to the promoter in response to P. Collectively, these data indicate that PIASy may be a useful target for down-regulation of MUC1 expression in various contexts.
Krüppel-Like Factor 9 Is a Negative Regulator of Ligand-Dependent Estrogen Receptor α Signaling in Ishikawa Endometrial Adenocarcinoma Cells
Authors: Velarde Michael C. , Zeng Zhaoyang , McQuown Jennelle R. , Simmen Frank A. , Simmen Rosalia C. M. 
Published: August 2007

AbstractEstrogen and progesterone, acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in uterine epithelial cells. Here we evaluated whether KLF9 may further support PR function by directly opposing estrogen receptor (ER) signaling. Using human Ishikawa endometrial epithelial cells, we showed that 17β-estradiol (E2)-dependent down-regulation of ERα expression was reversed by a small interfering RNA to KLF9. Transcription assays with the E2-sensitive 4× estrogen-responsive element-thymidine kinase-promoter-luciferase reporter gene demonstrated inhibition of ligand-dependent ERα transactivation with ectopic KLF9 expression. E2 induced PR-A/B and PR-B isoform expression in the absence of effects on KLF9 levels. Addition of KLF9 small interfering RNA augmented E2 induction of PR-A/B while abrogating that of PR-B, indicating selective E2-mediated inhibition of PR-A by KLF9. Chromatin immunoprecipitation of the ERα minimal promoter demonstrated KLF9 promotion of E2-dependent ERα association to a region containing functional GC-rich motifs. KLF9 inhibited the recruitment of the ERα coactivator specificity protein 1 (Sp1) to the PR proximal promoter region containing a half-estrogen responsive element and GC-rich sites, but had no effect on Sp1 association to the PR distal promoter region containing GC-rich sequences. In vivo association of KLF9 and Sp1, but not of ERα with KLF9 or Sp1, was observed in control and E2-treated cells. Our data identify KLF9 as a transcriptional repressor of ERα signaling and suggest that it may function at the node of PR and ER genomic pathways to influence cell proliferation.
Importance of Constitutive Activity and Arrestin-Independent Mechanisms for Intracellular Trafficking of the Ghrelin Receptor
Authors: Holliday Nicholas D. , Holst Birgitte , Rodionova Elena A. , Schwartz Thue W. , Cox Helen M. 
Published: August 2007

AbstractThe ghrelin receptor (GhrelinR) and its related orphan GPR39 each display constitutive signaling, but only GhrelinRs undergo basal internalization. Here we investigate these differences by considering the roles of the C tail receptor domains for constitutive internalization and activity. Furthermore the interaction between phosphorylated receptors and β-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved Gq signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal and substantially decreased agonist-induced internalization in transiently transfected HEK293 cells. Internalized GhrelinR and GhR-39 were predominantly localized to recycling compartments, identified with transferrin and the monomeric G proteins Rab5 and Rab11. Both the inverse agonist [d-Arg1, d-Phe5, d-Trp7,9, Leu11] substance P and a naturally occurring mutant GhrelinR (A204E) with eliminated constitutive activity inhibited basal GhrelinR internalization. Surprisingly, we found that noninternalizing GPR39 was highly phosphorylated and that basal and agonist-induced phosphorylation of the GhR-39 chimera was elevated compared with GhrelinRs. Moreover, basal GhrelinR endocytosis occurred without significant phosphorylation, and it was not prevented by cotransfection of a dominant-negative β-arrestin1(319–418) fragment or by expression in β-arrestin1/2 double-knockout mouse embryonic fibroblasts. In contrast, agonist-stimulated GhrelinRs recruited the clathrin adaptor green fluorescent protein-tagged β-arrestin2 to endosomes, coincident with increased receptor phosphorylation. Thus, GhrelinR internalization to recycling compartments depends on C-terminal motifs and constitutive activity, but the high levels of GPR39 phosphorylation, and of the GhR-39 chimera, are not sufficient to drive endocytosis. In addition, basal GhrelinR internalization occurs independently of β-arrestins.
Developing paediatric medicines: identifying the needs and recognizing the challenges
Authors: Ernest Terry B , Elder David P , Martini Luigi G , Roberts Matthew , Ford James L 
Published: August 2007

Abstract
There is a significant need for research and development into paediatric medicines. Only a small fraction of the drugs marketed and utilized as therapeutic agents in children have been clinically evaluated. The majority of marketed drugs are either not labelled, or inadequately labelled, for use in paediatric patients. The absence of suitable medicines or critical safety and efficacy information poses significant risks to a particularly vulnerable patient population. However, there are many challenges associated with developing medicines for the paediatric population and this review paper is intended to highlight these. The paediatric population is made up of a wide range of individuals of substantially varied physical size, weight and stage of physiological development. Experimentation on children is considered by many to be unethical, resulting in difficulties in obtaining critical safety data. Clinical trials are subject to detailed scrutiny by the various regulatory bodies who have recently recognized the need for pharmaceutical companies to invest in paediatric medicines. The costs associated with paediatric product development could result in poor or negative return on investment and so incentives have been proposed by the EU and US regulatory bodies. Additionally, some commonly used excipients may be unsuitable for use in children; and some dosage forms may be undesirable to the paediatric population.
A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest
Authors: Lu Xiao-Min , Yi Hong-Wei , Xu Jian-Liang , Sun Yang , Li Jian-Xin , Cao Shao-Xian , Xu Qiang 
Published: August 2007

Abstract
Oleanolic acid (3β-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3β)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOA-GMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.
Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells
Authors: Rytting Erik , Audus Kenneth L 
Published: August 2007

AbstractAlthough hypoxia is normal in early pregnancy, low placental oxygen concentrations later in pregnancy are often linked to complications such as pre-eclampsia and intrauterine growth restriction. The effects of low oxygen levels on drug and nutrient uptake via the organic cation transporter OCTN2 has been studied in BeWo cells, an in-vitro model of human trophoblast. BeWo cells were cultured under 20% (control) or 2% O2 (hypoxia) for 48 h before each experiment. In-vitro hypoxia was also simulated by the addition of CoCl2 to the cell culture medium. RT-PCR indicated increased transcription of OCTN2 in BeWo cells cultured under hypoxia, but Western blots did not show a corresponding increase in the amount of OCTN2 protein in the hypoxic cells compared with control. Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake. Decreased placental transport of carnitine may lead to symptoms of carnitine deficiency in infants from hypoxic pregnancies, whether caused by high altitude, pre-eclampsia or other factors. The OCTN1 substrate ergothioneine reversed the effects of hypoxia on carnitine transport, but identical concentrations of N-acetylcysteine, another water-soluble intracellular antioxidant, did not have the same effect.
Protective effect of (+)-catechin against gastric mucosal injury induced by ischaemia-reperfusion in rats
Authors: Rao Ch V , Vijayakumar M 
Published: August 2007

Abstract
Ischaemia and reperfusion are known to induce gastric lesions, predominantly due to excessive formation of reactive oxygen metabolites, adhesion of neutrophils to endothelial cells, microvascular dysfunction, gastric acid secretion, endogenous histamine and gastrin release. We have studied the effect of (+)-catechin on a gastric ulcer model involving damage to gastric injury by ischaemia-reperfusion (I/R) in rats. (+)-Catechin 50 mg kg−1 administered orally, once daily for three days after the initiation of I/R injury showed a significant (P &lt; 0.001) anti-ulcer activity against mucosal damage. However, (+)-catechin significantly decreased the lipid peroxidation and increased the level of catalase in the I/R condition. Elevated levels of alkaline phosphatase in the I/R group was significantly lowered (P &lt; 0.01) by (+)-catechin. The amount of H+K+ATPase was significantly decreased (P &lt; 0.001) in (+)-catechin-treated as compared with I/R rats. (+)-Catechin significantly decreased elevated plasma histamine (P &lt; 0.05) and corticosterone (P &lt; 0.05). The results suggested that (+)-catechin protected gastric mucosa against ischaemia-reperfusion-induced gastric ulcers by its antioxidant activity and mucus protection.
Involvement of kappa opioid receptors in formalin-induced inhibition of analgesic tolerance to morphine in mice
Authors: Tokuyama Shogo , Nagae Ryuji , Mashida Emiko , Hamabe Wakako 
Published: August 2007

Abstract
This study examined the role of kappa opioid receptors (KOR) in the mechanism underlying tolerance to the analgesic effects of morphine induced by chronic pain. The analgesic effect of morphine (10 mg kg−1), estimated by the tail-flick test in mice, gradually decreased during repeated daily morphine treatment. A significant decrease in the analgesic effect of morphine was seen on the fifth day of repeated morphine treatment compared with the first day. Chronic pain was induced by subcutaneous administration of 2% formalin into the dorsal part of the left hind paw, which significantly inhibited development of tolerance to morphine analgesia. The effect of formalin-induced pain on inhibition of morphine tolerance was reversed by the KOR antagonist nor-binaltorphimine. Furthermore, an antisense oligodeoxynucleotide, but not a missense oligodeoxynucleotide, against KOR completely suppressed the inhibitory effect of formalin-induced pain on morphine tolerance. Naltrindole, an antagonist of delta opioid receptor, did not affect chronic-pain-induced tolerance to morphine. Our findings show that the inhibitory effect of chronic pain on analgesic tolerance to morphine is mediated by KOR rather than delta opioid receptors.
Effects of water-soluble low-molecular-weight β-1, 3-D-glucan (branch β-1, 6) isolated from Aureobasidium pullulans 1A1 strain black yeast on restraint stress in mice
Authors: Kimura Yoshiyuki , Sumiyoshi Maho , Suzuki Takahiro , Suzuki Toshio , Sakanaka Masahiro 
Published: August 2007

Abstract
It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-γ and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight β-glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular-weight β-glucan at a dose of 50 or 100 mg kg−1 inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight β-glucan (100 mg kg−1) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight β-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecular-weight β-glucan may be an effective dietary supplement for the prevention of stress.
TSL Dissertation Abstracts—2006 Transportation Science and Logistics Society Dissertation Prize Competition
Authors: Mark Hickman 
Published: August 2007

The Transportation Science and Logistics (TSL) Society Dissertation Prize Competition is the oldest and most prestigious competition for doctoral dissertations in the field. The 2006 TSL dissertation prize committee consisted of Professor Michel Bierlaire (École Polytechnique Fédérale de Lausanne), Professor Ann Campbell (University of Iowa), Professor Alan Erera (Georgia Institute of Technology), Professor Donald Hearn (University of Florida), and Professor Mark Hickman (University of Arizona). Eligibility was limited to doctoral dissertations completed between June 1, 2005, and May 31, 2006, in the general area of transportation science and logistics. To be considered, a dissertation must have been nominated by the author’s thesis supervisor. This year we received 26 nominations from 24 universities and 10 countries, representing such diverse areas as vehicle routing, vehicle scheduling, traveler behavior, activity analysis, logistics, and supply chain management. This year’s pool of dissertations was exceptional in both its breadth and depth, showing remarkable theoretical and practical insights into many very interesting problems in transportation and logistics. With the large number of submissions and their exceptional quality, it was not easy for the committee to select a first place winner and an honorable mention. I would like to thank the authors, their advisors, and the prize committee for their part in this effort to recognize and honor the field’s outstanding doctoral researchers. Awards were announced at the TSL meeting at the 2006 INFORMS meeting in Pittsburgh. Perhaps without saying, the theses nominated for the TSL Dissertation Prize are distinguished by the fact that they were nominated for the award. Each dissertation makes a unique and valuable contribution to transportation science and logistics, and all entrants and their advisors deserve our sincere congratulations. Abstracts for the 26 dissertations follow; awardees are listed first, and finalists’ abstracts follow in alphabetical order by author. First Place: Christian Liebchen, Technische Universität Berlin, Germany. Advisors: Rolf H. Möhring and Karl Nachtigall. Title: “Periodic Timetable Optimization in Public Transport”. Honorable Mention: Anne Goodchild, University of California, Berkeley. Advisor: Carlos Daganzo. Title: “Crane Double Cycling in Container Ports: Algorithms, Evaluation, and Planning”.
Unlabeled Probes for the Detection and Typing of Herpes Simplex Virus
Authors: Dames Shale , Pattison David C , Bromley L Kathryn , Wittwer Carl T , Voelkerding Karl V 
Published: August 2007

Abstract
Background: Unlabeled probe detection with a double-stranded DNA (dsDNA) binding dye is one method to detect and confirm target amplification after PCR. Unlabeled probes and amplicon melting have been used to detect small deletions and single-nucleotide polymorphisms in assays where template is in abundance. Unlabeled probes have not been applied to low-level target detection, however.
Methods: Herpes simplex virus (HSV) was chosen as a model to compare the unlabeled probe method to an in-house reference assay using dual-labeled, minor groove binding probes. A saturating dsDNA dye (LCGreen® Plus) was used for real-time PCR. HSV-1, HSV-2, and an internal control were differentiated by PCR amplicon and unlabeled probe melting analysis after PCR.
Results: The unlabeled probe technique displayed 98% concordance with the reference assay for the detection of HSV from a variety of archived clinical samples (n = 182). HSV typing using unlabeled probes was 99% concordant (n = 104) to sequenced clinical samples and allowed for the detection of sequence polymorphisms in the amplicon and under the probe.
Conclusions: Unlabeled probes and amplicon melting can be used to detect and genotype as few as 10 copies of target per reaction, restricted only by stochastic limitations. The use of unlabeled probes provides an attractive alternative to conventional fluorescence-labeled, probe-based assays for genotyping and detection of HSV and might be useful for other low-copy targets where typing is informative.
Introduction
Authors: BORITZ J. EFRIM 
Published: August 2007

RÉSUMÉAfin de stimuler la réflexion et la discussion, le groupe de travail d'experts sur les marchés financiers (Capital Markets Leadership Task Force — CMLTF) a commandé un document de travail brossant le tableau de l'environnement actuel et approfondissant les questions clés que soulève le maintien de la qualité des marchés financiers canadiens. Ce document de travail porte sur la nature des marchés financiers canadiens, l'analyse des principaux éléments de l'environnement informationnel dans lequel ils évoluent et l'examen de la façon dont les principales parties prenantes contribuent à cet environnement. Il contient des suggestions quant aux mesures à prendre pour maintenir et améliorer l'attrait de ces marchés, en réduisant les risques inutiles d'une information erronée et, ce faisant, en s'assurant que les entreprises canadiennes ont accès aux capitaux au coût le plus bas, toutes choses étant égales. Le CMLTF a accepté le document de travail lors de sa réunion du 5 avril 2006, bien que les opinions qui y sont exprimées soient strictement celles de l'auteur et qu'elles puissent ne pas représenter celles des membres du groupe de travail. La version intégrale du document peut être téléchargée à partir du site Web du CMLTF, http:www.cmltf.ca. Puisque le document de travail avait pour but de stimuler la réflexion et la discussion, trois professeurs bien connus ont été invités à le commenter à la lumière des points de vue exprimés lors du congrès de décembre 2005 par les participants issus des principaux groupes de parties prenantes.
Improving Interim Reporting/L'Amélioration de L'Information Financière Intermédiaire
Authors: Wiedman Christine I. 
Published: August 2007

ABSTRACTThis paper is based on the Interim Reporting session of the Maintaining Quality Capital Markets through Quality Information Conference. Several significant initiatives relating to interim reporting were introduced and debated, including moving to a mandatory review regime in Canada and requiring firms to issue a review engagement report on the interim financial statements to the public. Conference participants were asked to vote on seven questions relating to these initiatives. This paper summarizes the results of the voting and discussion from the conference. Related academic research is also presented.RÉSUMÉLe présent article s'inspire de la séance du congrès sur le rôle de la qualité de l'information dans le maintien de la qualité des marchés financiers ayant porté sur l'information financière intermédiaire. Plusieurs projets importants relatifs à l'information financière intermédiaire ont été présentés et débattus, notamment la perspective du passage à un régime d'examen obligatoire au Canada et de l'obligation pour les entreprises de produire un rapport de mission d'examen des états financiers intermédiaires à l'intention du public. Les participants au congrès ont été appelés à voter sur sept questions relatives à ces projets. Le présent article résume les résultats du vote et les discussions tenues dans le cadre du congrès. Des recherches universitaires connexes sont également présentées.
Die Gestalt im Gesicht. Zur Figur Don Quijotes und zu den Strukturen literarischer Reputation
Authors: Witthaus Jan-Henrik 
Published: August 2007

Abstract
The central issue in the self-reflexive development of Don Quijote is an episode in Part I, 19, in which Sancho Panza names his master “Caballero de la Triste Figura.” The early German Quijote-translators Joachim Caesar, Friedrich Justin Bertuch, and Ludwig Tieck rendered the phrase as “Ritter (von) der traurigen Gestalt,” which has been repeatedly criticized. But we may ask whether the alleged mistranslation Gestalt does not have an impact on Cervantes's phrase and not, perhaps, disclose something in it. It may be argued that Figura anticipates the status of the knight as a literary figure. The premise of the second part of the novel is the popularity of the protagonist. The sobriquet that Sacho Panza gives to Don Quijote actually serves as a promise that is fulfilled in the second part of the novel.
Für Siegfried Jüttner zum 66. Geburtstag