bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR2 and CXCR4 regulate peripheral blood monocyte pharmacodynamics and link to efficacy in experimental autoimmune encephalomyelitis
Authors: Wang Yuanfan , Cui Long , Gonsiorek Waldemar , Min Soo-Hong , Anilkumar Gopinadhan , Rosenblum Stuart , Kozlowski Joseph , Lundell Daniel , Fine Jay S , Grant Ethan P 
Published: November 2009

Abstract

Background
CCR2 plays a key role in regulating monocyte trafficking to sites of inflammation and therefore has been the focus of much interest as a target for inflammatory disease.

Methods
Here we examined the effects of CCR2 blockade with a potent small molecule antagonist to determine the pharmacodynamic consequences on the peripheral blood monocyte compartment in the context of acute and chronic inflammatory processes.

Results
We demonstrate that CCR2 antagonism in vivo led to a rapid decrease in the number of circulating Ly6Chi monocytes and that this decrease was largely due to the CXCR4-dependent sequestration of these cells in the bone marrow, providing pharmacological evidence for a mechanism by which monocyte dynamics are regulated in vivo. CCR2 antagonism led to an accumulation of circulating CCL2 and CCL7 levels in the blood, indicating a role for CCR2 in regulating the levels of its ligands under homeostatic conditions. Finally, we show that the pharmacodynamic changes due to CCR2 antagonism were apparent after chronic dosing in mouse experimental autoimmune encephalomyelitis, a model in which CCR2 blockade demonstrated a dramatic reduction in disease severity, manifest in a reduced accumulation of monocytes and other cells in the CNS.

Conclusion
CCR2 antagonism in vivo has tractable pharmacodynamic effects that can be used to align target engagement with biologic effects on disease activity.
Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation
Authors: Carpenter Erica L , Mick Rosemarie , Rüter Jens , Vonderheide Robert H 
Published: November 2009

Abstract

Background
CD40 activation of antigen presenting cells (APC) such as dendritic cells (DC) and B cells plays an important role in immunological licensing of T cell immunity. Agonist CD40 antibodies have been previously shown in murine models to activate APC and enhance tumor immunity; in humans, CD40-activated DC and B cells induce tumor-specific T cells in vitro. Although clinical translation of these findings for patients with cancer has been previously limited due to the lack of a suitable and available drug, promising clinical results are now emerging from phase I studies of the agonist CD40 monoclonal antibody CP-870,893. The most prominent pharmacodynamic effect of CP-870,893 infusion is peripheral B cell modulation, but direct evidence of CP-870,893-mediated B cell activation and the potential impact on T cell reactivity has not been reported, despite increasing evidence that B cells, like DC, regulate cellular immunity.

Methods
Purified total CD19+ B cells, CD19+ CD27+ memory, or CD19+ CD27neg subsets from peripheral blood were stimulated in vitro with CP-870,893, in the presence or absence of the toll like receptor 9 (TLR9) ligand CpG oligodeoxynucleotide (ODN). B cell surface molecule expression and cytokine secretion were evaluated using flow cytometry. Activated B cells were used as stimulators in mixed lymphocyte reactions to evaluate their ability to induce allogeneic T cell responses.

Results
Incubation with CP-870,893 activated B cells, including both memory and naïve B cells, as demonstrated by upregulation of CD86, CD70, CD40, and MHC class I and II. CP-870,893-activated B cells induced T cell proliferation and T cell secretion of effector cytokines including IFN-gamma and IL-2. These effects were increased by TLR9 co-stimulation via a CpG ODN identical in sequence to a well-studied clinical grade reagent.

Conclusion
The CD40 mAb CP-870,893 activates both memory and naïve B cells and triggers their T cell stimulatory capacity. Simultaneous TLR9 ligation augments the effect of CP-870,893 alone. These results provide further rationale for combining CD40 and TLR9 activation using available clinical reagents in strategies of novel tumor immunotherapy.
Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes
Authors: Bar-Magen Tamara , Sloan Richard D , Faltenbacher Verena H , Donahue Daniel A , Kuhl Björn D , Oliveira Maureen , Xu Hongtao , Wainberg Mark A 
Published: November 2009

Abstract

Background
Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes.

Methods
This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors in vitro. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048.

Results
Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes.

Conclusion
This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.
Enhanced detection and study of murine norovirus-1 using a more efficient microglial cell line
Authors: Cox Courtney , Cao Shengbo , Lu Yuanan 
Published: November 2009

Abstract

Background
Human Noroviruses are the predominant cause of non-bacterial gastroenteritis worldwide. To facilitate prevention and control, a norovirus isolated from mice can provide a model to understand human noroviruses. To establish optimal viral infectivity conditions for murine noroviruses, several cell lines of hematopoietic lineage, including murine BV-2, RAW 264.7, and TIB, as well as human CHME-5, were tested comparatively for their sensitivity to murine norovirus-1.

Results
Except for CHME-5, all three murine-derived cell lines were susceptible to MNV infection. Viral infection of these cells was confirmed by RT-PCR. Using both viral plaque and replication assays, BV-2 and RAW 264.7 cells were determined to have comparable sensitivities to MNV-1 infection. Comparisons of cell growth characteristics, general laboratory handling and potential in-field applications suggest the use of BV-2 to be more advantageous.

Conclusion
Results obtained from these studies demonstrate that an immortalized microglial cell line can support MNV-1 replication and provides a more efficient method to detect and study murine noroviruses, facilitating future investigations using MNV-1 as a model to study, detect, and control Human Norovirus.
Incontinentia pigmenti presenting as hypodontia in a 3-year-old girl: a case report
Authors: Kitakawa Dárcio , Fontes Patrícia Campos , Magalhães Fernando Augusto Cintra , Almeida Janete Dias , Cabral Luiz Antonio Guimarães 
Published: November 2009

Abstract

Introduction
Incontinentia pigmenti or Bloch-Sulzberger syndrome is a rare X-linked dominant disease that mainly affects the skin, eyes, hair, central nervous system and teeth. The disease is predominant among women. Although dermatologic manifestations are among the most important aspects for the diagnosis of the syndrome, they are less damaging to the patient and do not require treatment. However, oral involvement characterized by hypodontia of deciduous and permanent teeth is important for the diagnosis and treatment of the patient.

Case presentation
We report the case of a 3-year-old girl with ophthalmologic and neurologic disturbances, cutaneous manifestations and hypodontia. Since the patient did not present more damaging manifestations such as neurologic and/or ophthalmologic problems, her most severe complications were related to dental anomalies. The importance of integrated dental treatment, which combines pediatric dentistry, orthodontics and conventional prosthesis, is emphasized.

Conclusion
Hypodontia is a frequent finding in incontinentia pigmenti, and dentists should be aware of this condition in order to help with the diagnosis.
Journal of Foot and Ankle Research, one year on
Authors: Potter Mike J , Menz Hylton B , Borthwick Alan M , Landorf Karl B 
Published: November 2009

AbstractJournal of Foot and Ankle Research was launched one year ago, and a number of its key achievements are highlighted in this editorial. Although the journal is underpinned by professional bodies associated with the podiatry professions in the UK and Australasia, its content is aimed at the wider foot and ankle research community. Nevertheless, the journal's achievements over the past year reflect the development of research in the profession of podiatry. From this perspective, the journal may be viewed as contributing to the overall attainment of some of the profession's key goals and strategic aims over the last decade, across the UK and Australasia. The journal has also witnessed policy changes in the last year, and these are discussed ‐ notably, the decision not to accept case reports for publication. We also report on a few of the key metrics, providing readers with a summary of the journal's performance over the last year.
Dynamic regulation of CD24 and the invasive, CD44posCD24negphenotype in breast cancer cell lines
Authors: Meyer Matthew J , Fleming Jodie M , Ali Mustapha A , Pesesky Mitchell W , Ginsburg Erika , Vonderhaar Barbara K 
Published: November 2009

Abstract
Introduction
The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24neg counterpart. Here we demonstrate that noninvasive, epithelial-like CD44posCD24pos cells readily give rise to invasive, mesenchymal CD44posCD24neg progeny in vivo and in vitro. This interconversion was found to be dependent upon Activin/Nodal signaling.

Methods
Breast cancer cell lines were sorted into CD44posCD24pos and CD44posCD24neg populations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts.

Results
CD24 expression was dynamically regulated in vitro in all evaluated breast cancer cell lines. Furthermore, a single noninvasive, epithelial-like CD44posCD24pos cell had the ability to give rise to invasive, mesenchymal CD44posCD24neg progeny. Importantly, this interconversion occurred in vivo as CD44posCD24pos cells gave rise to xenografts with locally invasive borders as seen in xenografts initiated with CD44posCD24neg cells. Lastly, the ability of CD44posCD24pos cells to give rise to mesenchymal progeny, and vice versa, was blocked upon ablation of Activin/Nodal signaling.

Conclusions
Our data demonstrate that the invasive, mesenchymal CD44posCD24neg phenotype is under dynamic control in breast cancer cell lines both in vitro and in vivo. Furthermore, our observations suggest that therapies targeting CD44posCD24neg tumor cells may have limited success in preventing primary tumor metastasis unless Activin/Nodal signaling is arrested.
Ku proteins interact with activator protein-2 transcription factors and contribute to ERBB2overexpression in breast cancer cell lines
Authors: Nolens Grégory , Pignon Jean-Christophe , Koopmansch Benjamin , Elmoualij Benaïssa , Zorzi Willy , De Pauw Edwin , Winkler Rosita 
Published: November 2009

Abstract
Introduction
Activator protein-2 (AP-2) α and AP-2γ transcription factors contribute to ERBB2 gene overexpression in breast cancer. In order to understand the mechanism by which the ERBB2 gene is overexpressed we searched for novel AP-2 interacting factors that contribute to its activity.

Methods
Ku proteins were identified as AP-2α interacting proteins by glutathione serine transferase (GST)-pull down followed by mass spectrometry. Transfection of the cells with siRNA, expression vectors and reporter vectors as well as chromatin immunoprecipitation (ChIP) assay were used to ascertain the implication of Ku proteins on ERBB2 expression.

Results
Nuclear proteins from BT-474 cells overexpressing AP-2α and AP-2γ were incubated with GST-AP2 or GST coated beads. Among the proteins retained specifically on GST-AP2 coated beads Ku70 and Ku80 proteins were identified by mass spectrometry. The contribution of Ku proteins to ERBB2 gene expression in BT-474 and SKBR3 cell lines was investigated by downregulating Ku proteins through the use of specific siRNAs. Depletion of Ku proteins led to downregulation of ERBB2 mRNA and protein levels. Furthermore, reduction of Ku80 in HCT116 cell line decreased the AP-2α activity on a reporter vector containing an AP-2 binding site linked to the ERBB2 core promoter, and transfection of Ku80 increased the activity of AP-2α on this promoter. Ku siRNAs also inhibited the activity of this reporter vector in BT-474 and SKBR3 cell lines and the activity of the ERBB2 promoter was further reduced by combining Ku siRNAs with AP-2α and AP-2γ siRNAs. ChIP experiments with chromatin extracted from wild type or AP-2α and AP-2γ or Ku70 siRNA transfected BT-474 cells demonstrated Ku70 recruitment to the ERBB2 proximal promoter in association with AP-2α and AP-2γ. Moreover, Ku70 siRNA like AP-2 siRNAs, greatly reduced PolII recruitment to the ERBB2 proximal promoter.

Conclusions
Ku proteins in interaction with AP-2 (α and γ) contribute to increased ERBB2 mRNA and protein levels in breast cancer cells.
Colchicine for the Primary and Secondary Prevention of Pericarditis: An Update
Authors: Kuo I fan , Pearson Glen J , Koshman Sheri L 
Published: November 2009

Objective: To review the efficacy and safety of colchicine as primary and secondary prophylaxis for pericarditis. Data Sources: We searched MEDLINE, EMBASE, PubMed, BSOSIS Previews. International Pharmaceutical Abstracts. Web of Science, and CENTRAL for controlled studies from database inception date to July 2009. Search terms included colchicine, pericarditis, and postpericardiotomy syndrome (PPS). Study Selection and Data Extraction: Prospective, randomized, controlled trials investigating the use of colchicine in preventing pericarditis were included. Data extracted included design, inclusion criteria, demographics, interventions, background therapy, and pericarditis-related clinical outcomes. Data Synthesis: Data were synthesized qualitatively, given variable study designs. Three trials were identified. A single trial examining primary prevention evaluated the use of colchicine versus placebo for preventing PPS in patients undergoing cardiopulmonary bypass grafting. No significant reduction in PPS was found. Two studies examined secondary prevention of pericarditis, comparing colchicine plus aspirin versus aspirin alone. One study examined using these comparators to treat a first episode of pericarditis. After 3 months, there was a significant reduction in recurrent pericarditis with colchicine plus aspirin (11.7% vs 33%; p = 0,009). Another study examined this same regimen in recurrent pericarditis, finding a significant reduction in recurrence after 6 months (21% vs 45%;p = 0.02). Conclusions: Despite limitations in study designs, current evidence suggests a role for colchicine in the secondary prophylaxis for recurrent pericarditis. The evidence for use of colchicine as primary prophylaxis in PPS is indeterminate; therefore, colchicine cannot be recommended routinely. While colchicine should be recommended for the prevention of recurrent pericarditis, questions regarding the optimal regimen and long-term safety profile need to be further elucidated.
Association Between Exposure to Topical Tacrolimus or Pimecrolimus and Cancers
Authors: Hui Rita L , Lide William , Chan James , Schottinger Joanne , Yoshinaga Monica , Millares Mirta 
Published: November 2009

Background: The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors. Objective: To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors. Methods: A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model. Results: Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma. Conclusions: Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.
Students' approaches to learning and their experiences of the teaching–learning environment in different disciplines
Authors: Parpala Anna. , Lindblom‐Ylänne Sari. , Komulainen Erkki. , Litmanen Topi. , Hirsto Laura. 
Published: November 2009

BackgroundThere is evidence of disciplinary variation in students' approaches to learning. Furthermore, previous research has shown that students' approaches are related to their perceptions of the learning environment.AimThe overall objective of the study was to analyse combinations of approaches to learning among undergraduates in different disciplines. More precisely, the aim was to cluster students on the basis of their scores on different items measuring approaches to learning, and to explore the relationship between the clusters and both the disciplines of the students and their perceptions of the teaching–learning environment.SampleA total of 2,509 students participated in the study.MethodsThe students were asked to complete an on‐line questionnaire, which was a revised version of the Experience of Teaching and Learning Questionnaire. It included items covering approaches to learning and perceptions of the teaching–learning environment.ResultsThe students were classified in four clusters. There were significant differences in how the respondents from the 10 faculties were represented in these clusters. There were also differences in their perceptions of the teaching–learning environment in the different faculties.ConclusionsIt appears that there is disciplinary variation in approaches to learning. Furthermore, the results indicate that both approaches to learning and the discipline have an effect on students' experiences of the teaching–learning environment.
Parental and school effects on children's political attitudes in Northern Ireland
Authors: Stringer Maurice. , Irwing Paul. , Giles Melanie. , McClenahan Carol. , Wilson Ronnie. , Hunter John. 
Published: November 2009

BackgroundRecent research has suggested that intergroup contacts with out‐group members can both reduce prejudice and is associated with attitude change.AimThis study extends prior work in Northern Ireland to examine parental and schooling effects on children's attitudes in a post‐conflict environment.SampleA large‐scale cross‐sectional survey of secondary schoolchildren (N = 1,732) and their parents (N = 800) in Northern Ireland assessed the effects of in‐school and out‐of‐school intergroup contacts on intergroup attitudes.MethodMultivariate analysis of variance was employed to examine associations between children's political attitudes and parental, group membership, school, and contact variables.ConclusionsThe results suggest that parental attitudes, group membership, and cross‐group contacts explain the majority of variance (58%) in children's political attitudes. The findings provide a comprehensive account of the factors that influence children's political attitudes within a deeply divided society and offer teachers and educationalists a way to improve community relations in a segregated society.
Medieninformatik in Studium und Lehre
Authors: Boll Susanne 
Published: November 2009

Zusammenfassung
Medieninformatik ist ein junges dynamisches Fachgebiet der Informatik, das in den vergangenen Jahren auch mehr und mehr in Studium und Lehre vertreten ist. Universitäten und Fachhochschulen haben eigene Studiengänge eingerichtet oder Schwerpunkte und Vertiefungsgebiete in den Informatikstudiengängen etabliert. Dieser Artikel trägt Ansichten zu den geeigneten Lehrinhalten für ein Curriculum der Medieninformatik zusammen. Er wirft einen Blick auf die unterschiedlichen Ausgestaltungen der Studienangebote auch mit der Fragestellung des konkreten Berufsbildes für die zukünftigen Medieninformatikerinnen und Medieninformatiker.
Medienkunst oder die Kunst die Medien zu erforschen
Authors: Beckhaus Steffi 
Published: November 2009

Zusammenfassung
Die Möglichkeiten und Wirkungsweisen von Medien lassen sich mit künstlerischen Projekten frei von Anforderungen an das Ergebnis oder ein Anwendungsziel entdecken und erforschen. Bereits in den 60er Jahren untersuchten sowohl Künstler als auch Ingenieure das Medium Computer künstlerisch und kreativ, um Einblicke in die Möglichkeiten des Computers zu bekommen. Ein aktuelles interaktives Beispiel, das die Fähigkeiten heutiger Computer nutzt und mit Hilfe des Computers als Medium tatsächliche prompte Interaktion zwischen Menschen ermöglicht, ist SoundVision, eine interaktive und kooperative audiovisuelle Installation. An verschiedenen vernetzten Stationen können mit unterschiedlichen Eingabegeräten “Klangbilder” erzeugt werden. Gespielte Musik erzeugt dabei ein Bild und Bilder aus Zeichnungen und Videos werden zusätzlich vertont. Zusammen ergeben sie jeweils einzelne TonBild-Stücke, die auf einer gemeinsamen Fläche kooperativ angeordnet werden können und dort ein gemeinsames TonBild entstehen lassen. Im Sinne einer Konversation arbeiten verschiedene Teilnehmer an verschiedenen Stationen gleichzeitig an einem gemeinsamen Werk. Das Werk materialisiert sich flüchtig im Sinne eines Konzerts. Es bleibt die notwendigerweise zuvor selbst entwickelte eigene Sprache der Teilnehmer ebenso wie das gegebenenfalls neu gewonnene Verständnis über BildTon Zusammenhänge und deren Ästhetik, über Kommunikation und das eingesetzte Medium als Solches — es entsteht Erfahrung, vielleicht sogar Erkenntnis über das Medium, das Medium wird erforscht. Diese Art Erfahrungen und Erkenntnisse aus künstlerisch motivierten Projekten lassen sich gewinnbringend auch in die Informatikforschung einbringen, auch wenn Ergebnisse daraus zunächst nicht quantifizierbar oder bewertbar sind. Experimentelle, spielerische, künstlerische Methoden haben einen wichtigen Anteil am Entstehen von Innovation und es wird motiviert, dass diese Methoden auch ihren Stellenwert und Raum in unserer Forschung erhalten.