bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptor Molecule Crk Is Required for Sustained Phosphorylation of Grb2-Associated Binder 1 and Hepatocyte Growth Factor–Induced Cell Motility of Human Synovial Sarcoma Cell Lines
Authors: Watanabe Takuya , Tsuda Masumi , Makino Yoshinori , Ichihara Shin , Sawa Hirofumi , Minami Akio , Mochizuki Naoki , Nagashima Kazuo , Tanaka Shinya 
Published: July 2006

Abstract
Activation of the c-Met receptor tyrosine kinase through its ligand, hepatocyte growth factor (HGF), promotes mitogenic, motogenic, and morphogenic cellular responses. Aberrant HGF/c-Met signaling has been strongly implicated in tumor cell invasion and metastasis. Both HGF and its receptor c-Met have been shown to be overexpressed in human synovial sarcoma, which often metastasizes to the lung; however, little is known about HGF-mediated biological effects in this sarcoma. Here, we provide evidence that Crk adaptor protein is required for the sustained phosphorylation of c-Met-docking protein Grb2-associated binder 1 (Gab1) in response to HGF, leading to the enhanced cell motility of human synovial sarcoma cell lines SYO-1, HS-SY-II, and Fuji. HGF stimulation induced the sustained phosphorylation on Y307 of Gab1 where Crk was recruited. Crk knockdown by RNA interference disturbed this HGF-induced tyrosine phosphorylation of Gab1. By mutational analysis, we identified that Src homology 2 domain of Crk is indispensable for the induction of the phosphorylation on multiple Tyr-X-X-Pro motifs containing Y307 in Gab1. HGF remarkably stimulated cell motility and scattering of synovial sarcoma cell lines, consistent with the prominent activation of Rac1, extreme filopodia formation, and membrane ruffling. Importantly, the elimination of Crk in these cells induced the disorganization of actin cytoskeleton and complete abolishment of HGF-mediated Rac1 activation and cell motility. Time-lapse microscopic analysis revealed the significant attenuation in scattering of Crk knockdown cells following HGF treatment. Furthermore, the depletion of Crk remarkably inhibited the tumor formation and its invasive growth in vivo. These results suggest that the sustained phosphorylation of Gab1 through Crk in response to HGF contributes to the prominent activation of Rac1 leading to enhanced cell motility, scattering, and cell invasion, which may support the crucial role of Crk in the aggressiveness of human synovial sarcoma. (Mol Cancer Res 2006;4(7):499–510)
Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells
Authors: Wolanin Kamila , Magalska Adriana , Mosieniak Grażyna , Klinger Rut , McKenna Sharon , Vejda Susanne , Sikora Ewa , Piwocka Katarzyna 
Published: July 2006

Abstract
The Bcr-Abl oncoprotein plays a major role in the development and progression of chronic myeloid leukemia and is a determinant of chemotherapy resistance occurring during the blast crisis phase of the disease. The aim of this article was to investigate the possibility of combating the resistance to apoptosis caused by Bcr-Abl by inducing an alternative cell death process. As a model of chronic myeloid leukemia, we employed Bcr-Abl-transfected mouse progenitor 32D cells with low and high Bcr-Abl expression levels corresponding to drug-sensitive and drug-resistant cells, respectively. The drug curcumin (diferuloylmethane), a known potent inducer of cell death in many cancer cells, was investigated for efficacy with Bcr-Abl-expressing cells. Curcumin strongly inhibited cell proliferation and affected cell viability by inducing apoptotic symptoms in all tested cells; however, apoptosis was a relatively late event. G2-M cell cycle arrest, together with increased mitotic index and cellular and nuclear morphology resembling those described for mitotic catastrophe, was observed and preceded caspase-3 activation and DNA fragmentation. Mitosis-arrested cells displayed abnormal chromatin organization, multipolar chromosome segregation, aberrant cytokinesis, and multinucleated cells—morphologic changes typical of mitotic catastrophe. We found that the mitotic cell death symptoms correlated with attenuated expression of survivin, a member of the chromosomal passenger complex, and mislocalization of Aurora B, the partner of survivin in the chromosomal passenger complex. Inhibition of survivin expression with small interfering RNA exhibited similar mitotic disturbances, thus implicating survivin as a major, albeit not the only, target for curcumin action. This study shows that curcumin can overcome the broad resistance to cell death caused by expression of Bcr-Abl and suggests that curcumin may be a promising agent for new combination regimens for drug-resistant chronic myeloid leukemia. (Mol Cancer Res 2006;4(7):457–69)
Akt1 Activation Can Augment Hypoxia-Inducible Factor-1α Expression by Increasing Protein Translation through a Mammalian Target of Rapamycin–Independent Pathway
Authors: Pore Nabendu , Jiang Zibin , Shu Hui-Kuo , Bernhard Eric , Kao Gary D. , Maity Amit 
Published: July 2006

Abstract
The phosphoinositide 3-kinase (PI3K)/Akt pathway is commonly activated in cancer; therefore, we investigated its role in hypoxia-inducible factor-1α (HIF-1α) regulation. Inhibition of PI3K in U87MG glioblastoma cells, which have activated PI3K/Akt activity secondary to phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation, with LY294002 blunted the induction of HIF-1α protein and its targets vascular endothelial growth factor and glut1 mRNA in response to hypoxia. Introduction of wild-type PTEN into these cells also blunted HIF-1α induction in response to hypoxia and decreased HIF-1α accumulation in the presence of the proteasomal inhibitor MG132. Akt small interfering RNA (siRNA) also decreased HIF-1α induction under hypoxia and its accumulation in normoxia in the presence of dimethyloxallyl glycine, a prolyl hydroxylase inhibitor that prevents HIF-1α degradation. Metabolic labeling studies showed that Akt siRNA decreased HIF-1α translation in normoxia in the presence of dimethyloxallyl glycine and in hypoxia. Inhibition of mammalian target of rapamycin (mTOR) with rapamycin (10-100 nmol/L) had no significant effect on HIF-1α induction in a variety of cell lines, a finding that was confirmed using mTOR siRNA. Furthermore, neither mTOR siRNA nor rapamycin decreased HIF-1α translation as determined by metabolic labeling studies. Therefore, our results indicate that Akt can augment HIF-1α expression by increasing its translation under both normoxic and hypoxic conditions; however, the pathway we are investigating seems to be rapamycin insensitive and mTOR independent. These observations, which were made on cells grown in standard tissue culture medium (10% serum), were confirmed in PC3 prostate carcinoma cells. We did find that rapamycin could decrease HIF-1α expression when cells were cultured in low serum, but this seems to represent a different pathway. (Mol Cancer Res 2006;4(7):471–9)
Tyrosines in the MUC1 Cytoplasmic Tail Modulate Transcription via the Extracellular Signal-Regulated Kinase 1/2 and Nuclear Factor-κB Pathways
Authors: Thompson Eric J. , Shanmugam Kandavel , Hattrup Christine L. , Kotlarczyk Kari L. , Gutierrez Albert , Bradley Judy M. , Mukherjee Pinku , Gendler Sandra J. 
Published: July 2006

Abstract
Much of the ability of the MUC1 oncoprotein to foster tumorigenesis and tumor progression likely originates from the interaction of its cytoplasmic tail with proteins involved in oncogenic signaling. Many of these interactions are regulated by phosphorylation, as the cytoplasmic tail contains seven highly conserved tyrosines and several serine/threonine phosphorylation sites. We have developed a cell line–based model system to study the effects of tyrosine phosphorylation on MUC1 signaling, with particular emphasis on its effects on gene transcription. COS-7 cells, which lack endogenous MUC1, were stably infected with wild-type MUC1 or a MUC1 construct lacking all seven tyrosines (MUC1 Y0) and analyzed for effects on transcription mediated by the extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) pathways. COS.MUC1 Y0 cells showed heightened active ERK1/2 with increased activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) transcriptional activity; there was also a simultaneous decrease in NF-κB transcriptional activity and nuclear localization. These changes altered the phenotype of COS.MUC1 Y0 cells, as this line displayed increased invasion and enhanced [3H]thymidine incorporation. Analysis of the three lines also showed significant differences in their cell cycle profile and bromodeoxyuridine incorporation when the cells were serum starved. These data support the growing evidence that MUC1 is involved in transcriptional regulation and link MUC1 for the first time to the NF-κB pathway. (Mol Cancer Res 2006;4(7):489–97)
An Autocrine Loop Involving Ret and Glial Cell–Derived Neurotrophic Factor Mediates Retinoic Acid–Induced Neuroblastoma Cell Differentiation
Authors: Cerchia Laura , D'Alessio Amelia , Amabile Giovanni , Duconge Frederic , Pestourie Carine , Tavitian Bertrand , Libri Domenico , de Franciscis Vittorio 
Published: July 2006

Abstract
In several neuroblastoma cell lines, retinoic acid (RA)–induced differentiation is coupled to increased expression of functional neurotrophic factor receptors, including Trk family receptors and the glial cell–derived neurotrophic factor receptor, Ret. In several cases, increased expression is dependent on signaling through TrkB. Unlike TrkA and TrkB, Ret has never been implicated as a prognostic marker for neuroblastomas. SK-N-BE(2) cells do not express any of Trk family receptors; therefore, they are a choice system to study the specific role of Ret in RA-induced differentiation. Using a 2′-fluoro-RNA aptamer and a truncated Ret protein as specific inhibitors of Ret, we show that RA-induced differentiation is mediated by a positive autocrine loop that sustains Ret downstream signaling and depends on glial cell–derived neurotrophic factor expression and release. This report shows that in SK-N-BE(2) cells, stimulation of Ret is a major upstream mechanism needed to mediate RA-induced differentiation. These results provide important insights on the molecular mechanism of RA action, which might be relevant for the development of biologically based therapeutic strategies. (Mol Cancer Res 2006;4(7):481–8)
'Power' and 'the Other' in Joshua: The Brutal Birthing of a Group Identity
Authors: Prior John Mansford 
Published: July 2006

AbstractIn a world marked by war, terrorism and ethnic cleansing, reading violent biblical writings such as the Book of Joshua has become problematic. This study probes the phenomenology of violence in Joshua in the light of analyses of state-instigated genocide by contemporary social and political scientists. With the aid of African scholar Mahmood Mamdani the cultural, economic and political group identity of Joshua's Israelites and their stigmatization of 'the other' is investigated. Then, with the help of studies on violence in Indonesia (Colombijn & Lindblad, 2002) where the author lives, the essay outlines seven missiological questions concerning the dynamics of brutality and the issue of 'power'. The contemporary reader may not be that distant from the mind-set of Joshua and, perhaps unconsciously, is engaged in prejudicial categorizing. Only after facing uncomfortable facts and our own ingrained fear can reconciliation move forward. Reading Joshua forces us to re-assess our place in our strife-torn world.
Conflicting Visions of Jonah – or Rather Diversity?
Authors: Bachmann Mercedes García 
Published: July 2006

AbstractIn conversation with a proposal that the book of Jonah was written as a reaction to the two apparently contradictory wisdom sayings of Proverbs 13:21 and Psalm 25:8, this paper reviews the book of Jonah in light of the two maxims from a Latin American perspective. Noting the element of surprise throughout the book, the author gives a contextual interpretation to the change of Jonah's appearance from dove (a passive character) to wolf (an enraged character) willing to die rather than witness God's mercy. As a missionary concern, the author parallels the anger of "Christian continent" (Latin America) against God's mercy for "outsiders" and the continent's self-righteousness with Jonah's enraged character. The self-righteousness is so strong that churches and congregations would rather die than open God's grace to others (Jonah 4). The paper concludes by stating that gender studies have alerted us to the danger of employing either/or (rather than both/and) and hierarchical (rather than egalitarian) categories and interpretations that do not leave sufficient space for diversity, both in the biblical text and in congregational life today.
The Genesis of Reconciliation: The Reconciliation of Genesis
Authors: Amos Clare 
Published: July 2006

AbstractThe article begins by explaining the reason for the author's selection of the motif of reconciliation as a key to understanding Genesis in missional terms. She draws attention to the fact that though 'reconciliation' is often linked to mission, in reality the theological connections between mission and reconciliation are not always clearly spelt out. Additionally Robert Schreiter's seminal work on the subject has largely ignored the Old Testament.The article then identifies the key episodes in Genesis where reconciliation is explored, that between Jacob and Esau and that between Joseph and his brothers. She draws attention to the way that these two scenes are in effect the climax of a motif which has run through the entire book, the relationship between 'pairs', and particularly between brothers. The article suggests that the theme of reconciliation as it is explored in Genesis offers a significant challenge to a too ready focus on particularity.
Thinking Mission with Paul and the Romans: Romans 15:1–33
Authors: Patte Daniel 
Published: July 2006

AbstractI write these notes on Romans 15:1–33 (read together with 1:1–15 and other passages of Romans) as resources for a group discussion of Romans 15 and its teaching about mission for the group's life context. I presuppose that the group will want to have three rounds of discussion. According to the size of the group these three rounds can take place in one long session – with the larger group breaking down in smaller groups and coming back together three times, for instance during an evening – or in three shorter sessions. The first round-table discussion is focused on the group members' first readings of Romans 15. The second round-table involves comparing the members' readings with those of scholars. For this purpose, since there are presently three types of scholarly readings of Romans, I present them, underscoring the different ways they conceive of Paul's teaching about mission. Throughout I also presuppose that each member of the group is committed to "read with" the other members this text of Paul as a Scripture about mission, a process that requires a third round-table.
Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative
Authors: Randi Maria Luigia , Putti Maria Caterina , Scapin Margherita , Pacquola Enrica , Tucci Fabio , Micalizzi Concetta , Zanesco Luigi , Fabris Fabrizio 
Published: July 2006

Abstract
Essential thrombocythemia (ET) is rare in children, and little or no information is available about clonality or JAK2 mutations. However, the analyses in this work prove useful for the diagnosis of adult myeloproliferative disorders (MPDs). We evaluated the clonality status and V617FJAK2 mutation in 20 children affected by ET and compared them with 47 consecutive adult ET cases. Clonality was evaluated on the DNA of granulocytes and on the RNA of platelets. V617FJAK2 was analyzed by sequencing tests, allele-specific polymerase chain reaction (PCR), and digestion by BsaXI. A monoclonal pattern was found in 4 (28.5%) of 14 children and in 45% of informative adults. Heterozygous V617FJAK2 was found less frequently in children than in adults (P < .009). Only 2 girls showed both the V617FJAK2 mutation and a monoclonal pattern; one of them was the only child presenting a major thrombotic complication. In contrast to adults, most children with ET do not show either a clonal disorder or the V617FJAK2 mutation.
Simulation of microarray data with realistic characteristics
Authors: Nykter Matti , Aho Tommi , Ahdesmäki Miika , Ruusuvuori Pekka , Lehmussola Antti , Yli-Harja Olli 
Published: July 2006

Abstract

Background
Microarray technologies have become common tools in biological research. As a result, a need for effective computational methods for data analysis has emerged. Numerous different algorithms have been proposed for analyzing the data. However, an objective evaluation of the proposed algorithms is not possible due to the lack of biological ground truth information. To overcome this fundamental problem, the use of simulated microarray data for algorithm validation has been proposed.

Results
We present a microarray simulation model which can be used to validate different kinds of data analysis algorithms. The proposed model is unique in the sense that it includes all the steps that affect the quality of real microarray data. These steps include the simulation of biological ground truth data, applying biological and measurement technology specific error models, and finally simulating the microarray slide manufacturing and hybridization. After all these steps are taken into account, the simulated data has realistic biological and statistical characteristics. The applicability of the proposed model is demonstrated by several examples.

Conclusion
The proposed microarray simulation model is modular and can be used in different kinds of applications. It includes several error models that have been proposed earlier and it can be used with different types of input data. The model can be used to simulate both spotted two-channel and oligonucleotide based single-channel microarrays. All this makes the model a valuable tool for example in validation of data analysis algorithms.
Environmental stress and reproduction in Drosophila melanogaster: starvation resistance, ovariole numbers and early age egg production
Authors: Wayne Marta L , Soundararajan Usha , Harshman Lawrence G 
Published: July 2006

Abstract

Background
The Y model of resource allocation predicts a tradeoff between reproduction and survival. Environmental stress could affect a tradeoff between reproduction and survival, but the physiological mechanisms underlying environmental mediation of the tradeoff are largely unknown. One example is the tradeoff between starvation resistance and early fecundity. One goal of the present study was to determine if reduced early age fecundity was indeed a robust indirect response to selection for starvation resistance, by investigation of a set of D. melanogaster starvation selected lines which had not previously been characterized for age specific egg production. Another goal of the present study was to investigate a possible relationship between ovariole number and starvation resistance. Ovariole number is correlated with maximum daily fecundity in outbred D. melanogaster. Thus, one might expect that a negative genetic correlation between starvation resistance and early fecundity would be accompanied by a decrease in ovariole number.

Results
Selection for early age female starvation resistance favored survival under food deprivation conditions apparently at the expense of early age egg production. The total number of eggs produced by females from selected and control lines was approximately the same for the first 26 days of life, but the timing of egg production differed such that selected females produced fewer eggs early in adult life. Females from lines selected for female starvation resistance exhibited a greater number of ovarioles than did unselected lines. Moreover, maternal starvation resulted in progeny with a greater number of ovarioles in both selected and unselected lines.

Conclusion
Reduced early age egg production is a robust response to laboratory selection for starvation survival. Ovariole numbers increased in response to selection for female starvation resistance indicating that ovariole number does not account for reduced early age egg production. Further, ovariole number increased in a parallel response to maternal starvation, suggesting an evolutionary association between maternal environment and the reproductive system of female progeny.
Chest radiography practice in critically ill patients: a postal survey in the Netherlands
Authors: Graat Marleen E , Hendrikse Karin A , Spronk Peter E , Korevaar Johanna C , Stoker Jaap , Schultz Marcus J 
Published: July 2006

AbstractBackgroundTo ascertain current chest radiography practice in intensive care units (ICUs) in the Netherlands.MethodsPostal survey: a questionnaire was sent to all ICUs with > 5 beds suitable for mechanical ventilation; pediatric ICUs were excluded. When an ICU performed daily-routine chest radiographs in any group of patients it was considered to be a "daily-routine chest radiography" ICU.ResultsFrom the number of ICUs responding, 63% practice a daily-routine strategy, in which chest radiographs are obtained on a daily basis without any specific reason. A daily-routine chest radiography strategy is practiced less frequently in university-affiliated ICUs (50%) as compared to other ICUs (68%), as well as in larger ICUs (> 20 beds, 50%) as compared to smaller ICUs (< 20 beds, 65%) (P> 0.05). Remarkably, physicians that practice a daily-routine strategy consider daily-routine radiographs helpful in guiding daily practice in less than 30% of all performed radiographs. Chest radiographs are considered essential for verification of the position of invasive devices (81%) and for diagnosing pneumothorax, pneumonia or acute respiratory distress syndrome (82%, 74% and 69%, respectively). On demand chest radiographs are obtained after introduction of thoracic drains, central venous lines and endotracheal tubes in 98%, 84% and 75% of responding ICUs, respectively. Chest films are also obtained in case of ventilatory deterioration (49% of responding ICUs), and after cardiopulmonary resuscitation (59%), tracheotomy (58%) and mini-tracheotomy (23%).ConclusionThere is notable lack of consensus on chest radiography practice in the Netherlands. This survey suggests that a large number of intensivists may doubt the value of daily-routine chest radiography, but still practice a daily-routine strategy.