bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progesterone Receptor-B Regulation of Insulin-Like Growth Factor–Stimulated Cell Migration in Breast Cancer Cells via Insulin Receptor Substrate-2
Authors: Ibrahim Yasir H. , Byron Sara A. , Cui Xiaojiang , Lee Adrian V. , Yee Douglas 
Published: September 2008

Abstract
Progesterone action contributes to the signaling of many growth factor pathways relevant to breast cancer tumor biology, including the insulin-like growth factor (IGF) system. Previous work has shown that insulin receptor substrate-2 (IRS-2) but not IRS-1 levels were regulated by progestin in progesterone receptor-B (PR-B) isoform expressing MCF-7 cells (C4-12 PR-B). Furthermore, type 1 IGF receptor (IGF1R) signaling via IRS-2 correlated with the increased cell migration observed in a number of breast cancer cell lines. Consequently, in this study, we examined whether the elevation of IRS-2 protein induced by progestin was sufficient to promote IGF-I–stimulated cell motility. Treatment of C4-12 PR-B cells with progestin shifted the balance of phosphorylation from IRS-1 to IRS-2 in response to IGF-I. This shift in IRS-2 activation was associated with enhanced migration in C4-12 PR-B cells pretreated with progestin, but had no effect on cell proliferation or survival. Treatment of C4-12 PR-B cells with RU486, an antiprogestin, inhibited IGF-induced cell migration. Attenuation of IRS-2 expression using small interfering RNA resulted in decreased IGF-stimulated motility. In addition, IRS-2 knockdown resulted in an abrogation of PKB/Akt phosphorylation but not mitogen-activated protein kinase. Consequently, LY294002, a phosphoinositide-3-kinase inhibitor, abolished IGF-induced cell motility in progestin-treated C4-12 PR-B cells. These data show a role for the PR in functionally promoting growth factor signaling, showing that levels of IRS proteins can determine IGF-mediated biology, PR-B signaling regulates IRS-2 expression, and that IRS-2 can mediate IGF-induced cell migration via phosphoinositide-3-kinase in breast cancer cells. (Mol Cancer Res 2008;6(9):1491–8)
Cultural Differences in Perception: Observations from a Remote Culture
Authors: Davidoff Jules , Fonteneau Elisabeth , Goldstein Julie 
Published: September 2008

AbstractPerceptual similarity was examined in a remote culture (Himba) and compared
to that of Western observers. Similarity was assessed in a relative size
judgement task and in an odd-one-out detection task. Thus, we examined the
effects of culture on what might be considered low-level visual abilities.
For both tasks, we found that performance was affected by stimuli that were
culturally relevant to the tasks. In Experiment 1, we showed that the use of
cow stimuli instead of the standard circles increased illusory strength for
the Himba. In Experiment 2, only the Himba showed more accurate detection
based on category differences in the displays. It is argued that that
Categorical Perception in Experiment 2, based on its presumed Whorfian
origins, was the more reliable procedure for examining the effects of
culture on perception.
Evidence Against Linguistic Relativity in Chinese and English: A Case Study of Spatial and Temporal Metaphors
Authors: Tse Chi-Shing , Altarriba Jeanette 
Published: September 2008

AbstractTo talk about time, English speakers often use horizontal spatial metaphors whereas Chinese speakers use both vertical and horizontal spatial metaphors. Boroditsky (2001) showed that while Chinese-English bilinguals were faster to verify a temporal target like June comes earlier than August after they had seen a vertical spatial prime rather than a horizontal spatial prime, English monolinguals showed the reverse pattern, thus supporting the linguistic relativity hypothesis. This finding was not conceptually replicated in January and Kako's (2007) six experiments for English monolinguals. In the current experiment, we failed to conceptually replicate her English monolinguals' findings: both Chinese-English bilinguals and English monolinguals were faster to verify the sentences after seeing a vertical spatial prime than a horizontal spatial prime. While we replicated Boroditsky's findings, in part, for our Chinese-English bilinguals, the similarity in the pattern of findings for both Chinese-English bilinguals and English monolinguals argues against the linguistic relativity hypothesis.
The Application of Uncitral Model Law Principles in the Middle East Region
Authors: Sadah Muhammad Abu , Norton Simon 
Published: September 2008

AbstractThis article presents an empirical analysis of the impact of the enforcement of substantive UNCITRAL Model Law principles in the Middle East region. Despite the main differences in the schools of thought and jurisdictions in the Middle East, the major conclusion is that UNCITRAL principles are applicable. As compared with data taken from legislations and case law after adopting the UNCITRAL Model Law, in an extension of the analysis, findings show a marginally significant change and deviations from the basic principles of the Model Law in these countries. Analysis of the implications of these changes from the perspective of the role played by the Model Law, shows that there was significant theoretical and practical negative impact upon the overall objectives of the law enforcement effort.
References to Islam and Women in the Afghan Constitution
Authors: Kamali Mohammad Hashim 
Published: September 2008

AbstractThis paper is presented in three parts and several sections. The first part consists of a stocktaking of recent developments and dynamics that have engaged President Hamid Karzai's government ever since he came to power in December 2001. A mixed picture is presented which draws attention to many problems that have impeded reconstruction efforts in the country. Some positive developments have also occurred including, for example, the introduction of a new constitution, presidential and parliamentary elections, as well as resumption of schooling for children that by mid-2006 had numbered four million throughout the country. An overview of the previous constitutions and a brief historical perspective attempt to show how leadership flaws and internal differences in the royal household plunged Afghanistan into a succession of coups, foreign invasions, and catastrophic consequences for its people. Are there any lessons to be learnt? The second part of this essay focuses on a review and analysis of the 2004 constitution with special reference to Islam, and the last part takes a similar approach to women's rights.
Altered States of Knowledge: The Attainment of Gnōsis in the Hermetica
Authors: Hanegraaff Wouter 
Published: September 2008

AbstractResearch into the so-called “philosophical” Hermetica has long been dominated by the foundational scholarship of André-Jean Festugière, who strongly emphasized their Greek and philosophical elements. Since the late 1970s, this perspective has given way to a new and more complex one, due to the work of another French scholar, Jean-Pierre Mahé, who could profit from the discovery of new textual sources, and called much more attention to the Egyptian and religious dimensions of the hermetic writings. This article addresses the question of how, on these foundations, we should evaluate and understand the frequent hermetic references to profound but wholly ineffable revelatory and salvational insights received during “ecstatic” states. Festugière dismissed them as “literary fictions”, whereas Mahé took them much more seriously as possibly reflecting ritual practices that took place in hermetic communities. Based upon close reading of three central texts (CH I, CH XIII, NH VI6), and challenging existing translations and interpretations, this article argues that the authors of the hermetic corpus assumed a sequential hierarchy of “levels of knowledge”, in which the highest and most profound knowledge (gnōsis) is attained only during ecstatic or “altered” states of consciousness that transcend rationality. While the hermetic teachings have often been described as unsystematic, inconsistent, incoherent or confused, in fact they are grounded in a precise and carefully formulated doctrine of how the hermetic initiate may move from the domain of mere rational discourse to the attainment of several “trans-rational” stages of direct experiential knowledge, and thereby from the limited and temporal domain of material reality to the unlimited and eternal one of Mind.
The Impact of Leadership on Student Outcomes: An Analysis of the Differential Effects of Leadership Types
Authors: Robinson Viviane M. J. , Lloyd Claire A. , Rowe Kenneth J. 
Published: September 2008

Purpose: The purpose of this study was to examine the relative impact of different types of leadership on students' academic and nonacademic outcomes.Research Design: The methodology involved an analysis of findings from 27 published studies of the relationship between leadership and student outcomes. The first meta-analysis, including 22 of the 27 studies, involved a comparison of the effects of transformational and instructional leadership on student outcomes. The second meta-analysis involved a comparison of the effects of five inductively derived sets of leadership practices on student outcomes. Twelve of the studies contributed to this second analysis.Findings: The first meta-analysis indicated that the average effect of instructional leadership on student outcomes was three to four times that of transformational leadership. Inspection of the survey items used to measure school leadership revealed five sets of leadership practices or dimensions: establishing goals and expectations; resourcing strategically; planning, coordinating, and evaluating teaching and the curriculum; promoting and participating in teacher learning and development, and ensuring an orderly and supportive environment. The second meta-analysis revealed strong average effects for the leadership dimension involving promoting and participating in teacher learning and development and moderate effects for the dimensions concerned with goal setting and planning, coordinating, and evaluating teaching and the curriculum.Conclusions and Implications for Research and Practice: The comparisons between transformational and instructional leadership and between the five leadership dimensions suggested that the more leaders focus their relationships, their work, and their learning on the core business of teaching and learning, the greater their influence on student outcomes. The article concludes with a discussion of the need for leadership research and practice to be more closely linked to the evidence on effective teaching and effective teacher learning. Such alignment could increase the impact of school leadership on student outcomes even further.
Management of Patients with ICDs at the End of Life (EOL): A Qualitative Study
Authors: Kelley Amy S. , Mehta Sonal S. , Carrington Reid M. 
Published: September 2008

Purpose. Implantable cardioverter defibrillator shocks at the end of life are distressing and warrant consideration of implantable cardioverter defibrillator deactivation discussions. A nationwide survey collected physicians' comments regarding such discussions. Methods. Vignettes ascertained respondents' practices regarding implantable cardioverter defibrillator deactivation discussions. Respondents' comments were analyzed to identify themes. Results. About 177 respondents (32%) provided 310 comments. One third reported that initiating the discussion would depend on specific circumstances, such as do not resuscitate status (35%); 21% advocated life-prolonging therapies; 17% said the patient/family or another physician should initiate the discussion; and 9% expressed inadequate education/awareness about implantable cardioverter defibrillator functions. Geriatricians and general internists expressed inadequate knowledge most frequently (12 writers, 75% in this theme), while electrophysiologists most frequently suggested further treatments/procedures (22 writers, 58%), and another doctor (13 writers, 76%) or the patient (8 writers, 62%) should begin the discussion. Conclusions. Improving the end of life care for patients with implantable cardioverter defibrillators will require additional physician education and increased commitment by subspecialists to deactivation discussions.
Imaging of plasmacytoid dendritic cell interactions with T cells
Authors: Mittelbrunn María , del Hoyo Gloria Martínez , López-Bravo María , Martín-Cofreces Noa B. , Scholer Alix , Hugues Stéphanie , Fetler Luc , Amigorena Sebastián , Ardavín Carlos , Sánchez-Madrid Francisco 
Published: September 2008

Abstract
Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferon and participate in adaptive immune responses, although the molecular interactions between pDCs and antigen-specific T cells remain unknown. This study examines immune synapse (IS) formation between murine pDCs and CD4+ T cells. Mature pDCs formed canonical ISs, involving relocation to the contact site of the microtubule-organizing center, F-actin, protein kinase C-θ, and pVav, and activation of early signaling molecules in T cells. However, immature pDCs were less efficient at forming conjugates with T cells and inducing IS formation, microtubule-organizing center translocation, and T-cell signaling and activation. Time-lapse videomicroscopy and 2-photon in vivo imaging of pDC–T-cell interactions revealed that immature pDCs preferentially mediated transient interactions, whereas mature pDCs promoted more stable contacts. Our data indicate that, under steady-state conditions, pDCs preferentially establish transient contacts with naive T cells and show a very modest immunogenic capability, whereas on maturation, pDCs are able to form long-lived contacts with T cells and significantly enhance their capacity to activate these lymphocytes.
Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins
Authors: Frecha Cecilia , Costa Caroline , Nègre Didier , Gauthier Emmanuel , Russell Stephen J. , Cosset François-Loïc , Verhoeyen Els 
Published: September 2008

AbstractA major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells such as primary T cells, which hampers their application for gene therapy. Here we generated high-titer LVs incorporating Edmonston measles virus (MV) glycoproteins H and F on their surface. They allowed efficient transduction through the MV receptors, SLAM and CD46, both present on blood T cells. Indeed, these H/F-displaying vectors outperformed by far VSV-G-LVs for the transduction of IL-7–prestimulated T cells. More importantly, a single exposure to these H/F-LVs allowed efficient gene transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need cell-cycle entry into the G1b phase for efficient transduction. High-level transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of target T-cell activation. Finally, the naive or memory phenotypes of transduced resting T cells were maintained and no changes in cytokine profiles were detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV transduction of resting T cells overcomes the limitation of current lentiviral vectors and may improve the efficacy of T cell–based gene therapy.
Cyclic AMP plays a critical role in C3a-receptor–mediated regulation of dendritic cells in antigen uptake and T-cell stimulation
Authors: Li Ke , Anderson Katie J. , Peng Qi , Noble Alistair , Lu Bao , Kelly Adrian P. , Wang Naiyin , Sacks Steven H. , Zhou Wuding 
Published: September 2008

AbstractThe biochemical basis for complement acting directly on antigen-presenting cells to enhance their function in T-cell stimulation has been unclear. Here we present evidence that engagement of C3a receptor (C3aR) on the surface of dendritic cells (DCs) leads to alterations in the level of intracellular cyclic adenosine monophosphate (cAMP), a potent negative regulator of inflammatory cytokines. C3aR activation-induced depression of cAMP was associated with enhanced capacity of DCs for antigen uptake and T-cell stimulation. Conversely, C3aR-deficient DCs showed elevation of cAMP and impaired properties for antigen uptake and immune stimulation. Similarities in the phenotype of C3-deficient and C3aR-deficient DCs suggest that local production of C3 with extracellular metabolism to C3a is an important driver of DC alterations in cAMP. The finding of a link between complement and adaptive immune stimulation through cAMP offers new insight into how innate and adaptive immunity combine to generate efficient effector and memory responses.
Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA
Authors: Chu Charles C. , Catera Rosa , Hatzi Katerina , Yan Xiao-Jie , Zhang Lu , Wang Xiao Bo , Fales Henry M. , Allen Steven L. , Kolitz Jonathan E. , Rai Kanti R. , Chiorazzi Nicholas 
Published: September 2008

AbstractLeukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells.
Central role of Sp1-regulated CD39 in hypoxia/ischemia protection
Authors: Eltzschig Holger K. , Köhler David , Eckle Tobias , Kong Tianqing , Robson Simon C. , Colgan Sean P. 
Published: September 2008

AbstractHypoxia is common to several inflammatory diseases, where multiple cell types release adenine-nucleotides (particularly adenosine triphosphate/adenosine diphosphate). Adenosine triphosphate/adenosine diphosphate is metabolized to adenosine through a 2-step enzymatic reaction initiated by CD39 (ectonucleoside-triphosphate-diphosphohydrolase-1). Thus, extracellular adenosine becomes available to regulate multiple inflammatory endpoints. Here, we hypothesized that hypoxia transcriptionally up-regulates CD39 expression. Initial studies revealed hypoxia-dependent increases in CD39 mRNA and immunoreactivity on endothelia. Examination of the human CD39 gene promoter identified a region important in hypoxia inducibility. Multiple levels of analysis, including site-directed mutagenesis, chromatin immunoprecipitation, and inhibition by antisense, revealed a critical role for transcription-factor Sp1 in hypoxia-induction of CD39. Using a combination of cd39−/− mice and Sp1 small interfering RNA in in vivo cardiac ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial ischemia. In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia.
FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects
Authors: Lagorce David , Sperandio Olivier , Galons Hervé , Miteva Maria A , Villoutreix Bruno O 
Published: September 2008

Abstract

Background
Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making.

Results
This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries.

Conclusion
We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.
A novel reverse transduction adenoviral array for the functional analysis of shRNA libraries
Authors: Oehmig Angelika , Klotzbücher Andrea , Thomas Maria , Weise Frank , Hagner Ursula , Brundiers Ralf , Waldherr Dirk , Lingnau Andreas , Knappik Achim , Kubbutat Michael HG , Joos Thomas O , Volkmer Hansjürgen 
Published: September 2008

Abstract

Background
The identification of novel drug targets by assessing gene functions is most conveniently achieved by high-throughput loss-of-function RNA interference screening. There is a growing need to employ primary cells in such screenings, since they reflect the physiological situation more closely than transformed cell lines do. Highly miniaturized and parallelized approaches as exemplified by reverse transfection or transduction arrays meet these requirements, hence we verified the applicability of an adenoviral microarray for the elucidation of gene functions in primary cells.

Results
Here, we present microarrays of infectious adenoviruses encoding short hairpin RNA (shRNA) as a new tool for gene function analysis. As an example to demonstrate its application, we chose shRNAs directed against seven selected human protein kinases, and we have performed quantitative analysis of phenotypical responses in primary human umbilical vein cells (HUVEC). These microarrays enabled us to infect the target cells in a parallelized and miniaturized procedure without significant cross-contamination: Viruses were reversibly immobilized in spots in such a way that the seeded cells were confined to the area of the viral spots, thus simplifying the subsequent addressing of genetically modified cells for analysis. Computer-assisted image analysis of fluorescence images was applied to analyze the cellular response after shRNA expression. Both the expression level of knock-down target proteins as well as the functional output as measured by caspase 3 activity and DNA fractionation (TUNEL) were quantified.

Conclusion
We have developed an adenoviral microarray technique suitable for miniaturized and parallelized analysis of gene function. The practicability of this technique was demonstrated by the analysis of several kinases involved in the activation of programmed cell death, both in tumor cells and in primary cells.