bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel DNMT3B Splice Variant Expressed in Tumor and Pluripotent Cells Modulates Genomic DNA Methylation Patterns and Displays Altered DNA Binding
Authors: Gopalakrishnan Suhasni , Van Emburgh Beth O. , Shan Jixiu , Su Zhen , Fields C. Robert , Vieweg Johannes , Hamazaki Takashi , Schwartz Philip H. , Terada Naohiro , Robertson Keith D. 
Published: October 2009

Abstract
DNA methylation is an epigenetic mark essential for mammalian development, genomic stability, and imprinting. DNA methylation patterns are established and maintained by three DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B. Interestingly, all three DNMTs make use of alternative splicing. DNMT3B has nearly 40 known splice variants expressed in a tissue- and disease-specific manner, but very little is known about the role of these splice variants in modulating DNMT3B function. We describe here the identification and characterization of a novel alternatively spliced form of DNMT3B lacking exon 5 within the NH2-terminal regulatory domain. This variant, which we term DNMT3B3Δ5 because it is closely related in structure to the ubiquitously expressed DNMT3B3 isoform, is highly expressed in pluripotent cells and brain tissue, is downregulated during differentiation, and is conserved in the mouse. Creation of pluripotent iPS cells from fibroblasts results in marked induction of DNMT3B3Δ5. DNMT3B3Δ5 expression is also altered in human disease, with tumor cell lines displaying elevated or reduced expression depending on their tissue of origin. We then compared the DNA binding and subcellular localization of DNMT3B3Δ5 versus DNMT3B3, revealing that DNMT3B3Δ5 possessed significantly enhanced DNA binding affinity and displayed an altered nuclear distribution. Finally, ectopic overexpression of DNMT3B3Δ5 resulted in repetitive element hypomethylation and enhanced cell growth in a colony formation assay. Taken together, these results show that DNMT3B3Δ5 may play an important role in stem cell maintenance or differentiation and suggest that sequences encoded by exon 5 influence the functional properties of DNMT3B. (Mol Cancer Res 2009;7(10):1622–34)
A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells
Authors: Hofmann Marco H. , Heinrich Jochen , Radziwil Gerald , Moelling Karin 
Published: October 2009

Abstract
The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1–specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635–44)
Amplification of Lipopolysaccharide-Induced Cytokine Synthesis in Non–Small Cell Lung Cancer/Neutrophil Cocultures
Authors: Grandel Ulrich , Heygster Diana , Sibelius Ulf , Fink Ludger , Sigel Stefanie , Seeger Werner , Grimminger Friedrich , Hattar Katja 
Published: October 2009

Abstract
Proinflammatory cytokines are centrally involved in tumor progression and survival in non–small cell lung cancer, and both the presence of infiltrating neutrophils and bacterial infection in the lung may indicate a poor prognosis. Against this background, we investigated the effect of the bacterial cell wall component lipopolysaccharide (LPS) on interleukin (IL)-6 and IL-8 synthesis in the non–small cell lung cancer line A549 and in A549-neutrophil cocultures. The LPS induced a dose-dependent and time-dependent release of IL-8 from A549 cells, whereas IL-6 could not be detected. Interestingly, in A549-neutrophil cocultures, IL-8 synthesis was massively amplified and IL-6 was also released, compared with the respective monocultures. The A549 cells were identified as the primary cellular source of these cytokines, as enhanced cytokine mRNA transcription was detected in this cell type, although not in neutrophils in the coculture system. Experiments done in transwells indicated that direct cell-cell contact was a prerequisite for the increased cytokine generation. Inhibition of tumor necrosis factor-α bioactivity by neutralizing antibodies and blocking cyclooxygenase-2 activity blunted the enhanced cytokine generation in the coculture system. Amplification of LPS-induced cytokine secretion could be reproduced when the small cell lung cancer cell line H69 was cocultured with neutrophils. When the Gram-positive cell wall component lipoteichoic acid was used instead of LPS, cytokine synthesis was also amplified in A549-neutrophil cocultures, to a similar extent to that observed with LPS. These data indicate that interaction between bacterial pathogens, neutrophils, and tumor cells might amplify the release of proinflammatory cytokines which may promote tumor growth in vivo. (Mol Cancer Res 2009;7(10):1729–35)
Expression of PGK1 by Prostate Cancer Cells Induces Bone Formation
Authors: Jung Younghun , Shiozawa Yusuke , Wang Jianhua , Wang Jingcheng , Wang Zhuo , Pedersen Elisabeth A. , Lee Clara H. , Hall Christopher L. , Hogg Phillip J. , Krebsbach Paul H. , Keller Evan T. , Taichman Russell S. 
Published: October 2009

Abstract
Prostate cancer (PCa) is one of the solid tumors that metastasize to the bone. Once there, the phenotype of the bone lesions is dependent upon the balance between osteoblastogenesis and osteoclastogenesis. We previously reported that overexpression of phosphoglycerate kinase 1 (PGK1) in PCa cell lines enhanced bone formation at the metastatic site in vivo. Here, the role of PGK1 in the bone formation was further explored. We show that PCa-derived PGK1 induces osteoblastic differentiation of bone marrow stromal cells. We also found that PGK1 secreted by PCa inhibits osteoclastogenesis. Finally, the expression levels of the bone-specific markers in PCa cells were higher in cells overexpressing PGK1 than controls. Together, these data suggest that PGK1 secreted by PCa regulates bone formation at the metastatic site by increasing osteoblastic activity, decreasing osteoclastic function, and expressing an osteoblastic phenotype by PCa cells. (Mol Cancer Res 2009;7(10):1595–604)
Shin Buddhism, Authority, and the Fundamental Law of Education
Authors: Dessì Ugo 
Published: October 2009

AbstractThis article takes its cue from one of the most controversial issues in the contemporary Japanese scene, the 2006 complete revision of the Fundamental Law of Education, that includes among its objectives the cultivation of patriotism, the high evaluation of Japanese tradition and culture, and the promotion of general knowledge regarding religion in public schools. Within this framework, the role of religion in education indeed represents a sensitive subject, which entails once again reinterpretation of the issues of the separation of state and religion, and the freedom of religion, which are enshrined in the Japanese Constitution. There have been reactions to this revision from various religious institutions, ranging from support to overt opposition. What is argued here is that these responses are meaningful to understanding some of the major dynamics currently at work within the Japanese religious world, and their implications for the issue of religion and authority. In this respect, the Shin Buddhist position may be seen as a way of contesting the claims of authority by political institutions, and affirming an alternative authoritative discourse on the basis of selected doctrinal sources, and a positive approach toward globalization and the differentiation of religion, politics and education.
Immediacy, Mediation, and Media in Early Modern Catholic and Protestant Representations of Safavid Iran
Authors: Brentjes Sonja 
Published: October 2009

AbstractIn this paper I argue that none of the sources produced by European visitors to Safavid Iran are unmediated, immediate expressions of observations, experiences, emotions and descriptions of the country's nature and culture. I offer as evidence different kinds of textual sources created by four travelers in the early seventeenth century, maps of Iran produced in various European cities and prints and engravings made by artists. I show that partly contradictory discourses governed these textual and visual representations of Iran and that particularities of each kind shaped the practices and norms of the creation of its individual representatives.
Anatomical Confirmation of the Use of Radiographic Landmarks in Medial Patellofemoral Ligament Reconstruction
Authors: Redfern John , Kamath Ganesh , Burks Robert 
Published: October 2009

Background A recent study has described radiographic landmarks for femoral insertion of the medial patellofemoral ligament. Clinical relevance and application of these landmarks for surgical reconstruction have yet to be determined. Hypothesis Radiographic landmarks can be used to accurately determine the femoral insertion of the medial patellofemoral ligament in a percutaneous fluoroscopically guided surgical technique. Study Design Descriptive laboratory study Methods The femoral insertion of the medial patellofemoral ligament was estimated using fluoroscopy in 8 fresh-frozen human cadaveric knees. The knees were dissected and the true anatomical medial patellofemoral ligament femoral insertion was identified. Radiographic markers were placed on both the estimated and anatomical medial patellofemoral ligament and a repeat lateral radiograph was performed. Using imaging software, the distance between the true anatomical insertion and the fluoroscopically determined insertion was calculated. Results All 8 points determined by fluoroscopically guided pin placement averaged less than 4 mm from the anatomical insertion. The radiographic landmark method consistently placed the origin on average 2.5 mm anterior and 0.6 mm distal to the anatomical insertion. Conclusion Radiographic landmarks determined by fluoroscopy can be used to accurately reproduce the femoral insertion of the medial patellofemoral ligament in ligament reconstruction. Clinical Relevance Confirming the use of radiographic landmarks to determine the medial patellofemoral ligament femoral insertion may help to increase accuracy and precision in ligament reconstruction and minimize surgical dissection.
Association Between ApoE4 Allele and Deep Venous Thrombosis: A Pilot Study
Authors: Katrancioglu Nurkay , Manduz Sinasi , Ozen Filiz , Yilmaz Mehmet Birhan , Atahan Erhan , Ozdemir Ozturk , Berkan Ocal 
Published: October 2009

Introduction: Deep vein thrombosis (DVT) is a multifactorial disease with genetic and acquired risk factors playing in concert in its pathogenesis. ApoE gene polymorphisms seem to have some impact among patients with cardiovascular disease; however, association between DVT and ApoE gene polymorphism has not been evaluated. Materials and Methods: We aimed to search the relative frequencies ApoE alleles among patients with DVT and healthy participants. We enrolled 59 consecutive patients with DVT and 59 age- and sex-matched healthy controls. Results: In the DVT group, E3/E4 gene polymorphism was detected in 20 patients (33.9%), in the control group E3/E4 polymorphism was detected in six patients (10.2%; P = .002). In the multivariable regression analysis, E3/E4 was independently associated with 1.31-fold increased risk of DVT (odds ratio [OR] 1.31; 95% confidence interval [CI], 1.30-10.48). Conclusion: It seems there is a relationship between ApoE3/E4 gene polymorphism and DVT in the Turkish population. However, this pilot study should be supported with large-scale studies.
Pioglitazone improves superoxide dismutase mediated vascular reactivity in the obese Zucker rat
Authors: Dorafshar Amir H. , Moodley Kogie , Khoe Michelle , Lyon Chris , Bryer-Ash Michael 
Published: October 2009

Objective: To test the hypothesis that the thiazolidinedione agent, pioglitazone, mediates its chronic BP lowering action via improving vascular reactivity. Methods and Results: Lean (Fa/fa) and obese (fa/fa) Zucker rats were treated with or without pioglitazone (20 mg/ kg/day) for 4 weeks (n=8 animals per group). Pioglitazone treatment was associated with a significant improvement in oral glucose tolerance in the obese animals (p<0.05 compared with untreated obese). Pioglitazone prevented the development of hypertension seen in obese untreated rats (SBP 126±1 versus 138±1 mmHg; p<0.0001). Aortic ring preparations from pioglitazone-treated obese rats showed improved relaxation responsiveness (ED50 0.28 versus 1.15 U/ ml, p<0.001) to SOD, a NO potentiator, compared with untreated obese animals. Conclusions: SOD-mediated vasorelaxation may contribute to the chronic antihypertensive effect and/or the improvement in insulin sensitivity following pioglitazone treatment.
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome
Authors: Luesink Maaike , Pennings Jeroen L. A. , Wissink Willemijn M. , Linssen Peter C. M. , Muus Petra , Pfundt Rolph , de Witte Theo J. M. , van der Reijden Bert A. , Jansen Joop H. 
Published: October 2009

Abstract
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide can induce a differentiation syndrome (DS) with massive pulmonary infiltration of differentiating leukemic cells. Because chemokines are implicated in migration and extravasation of leukemic cells, chemokines might play a role in DS. ATRA stimulation of the APL cell line NB4 induced expression of multiple CC-chemokines (CCLs) and their receptors (> 19-fold), resulting in increased chemokine levels and chemotaxis. Induction of CCL2 and CCL24 was directly mediated by ligand-activated retinoic acid receptors. In primary leukemia cells derived from APL patients at diagnosis, ATRA induced chemokine production as well. Furthermore, in plasma of an APL patient with DS, we observed chemokine induction, suggesting that chemokines might be important in DS. Dexamethasone, which efficiently reduces pulmonary chemokine production, did not inhibit chemokine induction in APL cells. Finally, chemokine production was also induced by arsenic trioxide as single agent or in combination with ATRA. We propose that differentiation therapy may induce chemokine production in the lung and in APL cells, which both trigger migration of leukemic cells. Because dexamethasone does not efficiently reduce leukemic chemokine production, pulmonary infiltration of leukemic cells may induce an uncontrollable hyperinflammatory reaction in the lung.
Systematic in vivo structure-function analysis of p300 in hematopoiesis
Authors: Kimbrel Erin A. , Lemieux Madeleine E. , Xia Xiaobo , Davis Tina N. , Rebel Vivienne I. , Kung Andrew L. 
Published: October 2009

AbstractCyclic adenosine monophosphate response element binding (CREB)–binding protein (CBP) and p300 are multidomain transcriptional coactivators that help assemble large regulatory complexes at sites of active transcription. Nullizygosity of CBP or p300 results in pervasive defects in hematopoiesis. To systematically assess the structural domains of p300 required for normal hematopoiesis, we used recombinase-mediated cassette exchange to create an allelic series of coisogenic embryonic stem cells, each expressing a different mutant of p300 from the endogenous locus. We found that deletion of either the KIX or CH1 domain caused profound and pervasive defects in hematopoiesis, whereas the loss of most other domains had only lineage-restricted effects. When expressed from the p300 locus, an extra copy of CBP largely compensated for a lack of p300. Surprisingly, mutation of the p300 histone acetyltransferase (HAT) domain had minimal effects on hematopoiesis, and actually increased progenitor and stem cell numbers and proliferative potential. Our results suggest that, in distinct contrast to other organ systems, HAT activity does not provide a critical function for hematopoietic development and emphasizes the importance of enzyme-independent functions of p300.
Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit
Authors: Gutman Jonathan A. , Turtle Cameron J. , Manley Thomas J. , Heimfeld Shelly , Bernstein Irwin D. , Riddell Stanley R. , Delaney Colleen 
Published: October 2009

AbstractWe investigated the potential role of an immune reaction in mediating the dominant engraftment of 1 cord blood unit in 14 patients who received a double-unit cord blood transplantation (CBT). In 10 patients, dominant engraftment of a single donor unit emerged by day 28 after CBT. In 9 of these 10 patients, a significant subset of CD8+ CD45RO+/−CCR7− T cells, present in peripheral blood mononuclear cells and derived from the engrafting cord blood unit, produced interferon-γ (IFN-γ) in response to the nonengrafting unit. No significant population of IFN-γ–secreting cells was detectable when posttransplantation peripheral blood mononuclear cells were stimulated against cells from the engrafted unit (P < .001) or from a random human leukocyte antigen disparate third party (P = .003). Three patients maintained persistent mixed chimerism after CBT, and no significant IFN-γ–secreting cells were detected after similar stimulations in these patients (P < .005). Our data provide the first direct evidence in human double-unit CBT recipients that immune rejection mediated by effector CD8+ T cells developing after CBT from naive precursors is responsible for the failure of 1 unit to engraft. Future investigations based on these findings may result in strategies to predict a dominant unit and enhance graft-versus-leukemia effect.
Endothelial cell ADAMTS-13 and VWF: production, release, and VWF string cleavage
Authors: Turner Nancy A. , Nolasco Leticia , Ruggeri Zaverio M. , Moake Joel L. 
Published: October 2009

Abstract
Human umbilical vein endothelial cell (HUVEC)–released ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin repeats) and HUVEC-secreted von Willebrand factor (VWF) strings were investigated under static conditions that allow the accumulation and analysis of ADAMTS-13. The latter was released constitutively from HUVECs and cleaved the secreted and cell-anchored VWF strings progressively during 15 minutes in Ca2+/Zn2+-containing buffer. HUVEC ADAMTS13 mRNA expression was approximately 1:100 of VWF monomeric subunit expression. In contrast to multimeric VWF stored within Weibel-Palade bodies and secreted rapidly in response to cell stimulation, ADAMTS-13 was released directly from the Golgi to the cell exterior without an organelle storage site. The constitutive release of ADAMTS-13 continued at the same slow rate regardless of the presence or absence of histamine stimulation of HUVECs. Consequently, the percentage of VWF strings cleaved by ADAMTS-13 at VWF Y1605-M1606 decreased as the rate of VWF string secretion was increased by cell stimulation. Blockade of HUVEC ADAMTS-13 activity by antibodies to different ADAMTS-13 domains made it possible to detect the attachment of ADAMTS-13 all along the lengths of HUVEC-secreted VWF strings. Constitutive ADAMTS-13 released from endothelial cells may contribute to the maintenance of cell surfaces free of hyperadhesive VWF multimeric strings.
Gene expression analysis of the biocontrol fungus Trichoderma harzianum in the presence of tomato plants, chitin, or glucose using a high-density oligonucleotide microarray
Authors: Samolski Ilanit , de Luis Alberto , Vizcaíno Juan Antonio , Monte Enrique , Suárez M Belén 
Published: October 2009

Abstract

Background
It has recently been shown that the Trichoderma fungal species used for biocontrol of plant diseases are capable of interacting with plant roots directly, behaving as symbiotic microorganisms. With a view to providing further information at transcriptomic level about the early response of Trichoderma to a host plant, we developed a high-density oligonucleotide (HDO) microarray encompassing 14,081 Expressed Sequence Tag (EST)-based transcripts from eight Trichoderma spp. and 9,121 genome-derived transcripts of T. reesei, and we have used this microarray to examine the gene expression of T. harzianum either alone or in the presence of tomato plants, chitin, or glucose.

Results
Global microarray analysis revealed 1,617 probe sets showing differential expression in T. harzianum mycelia under at least one of the culture conditions tested as compared with one another. Hierarchical clustering and heat map representation showed that the expression patterns obtained in glucose medium clustered separately from the expression patterns observed in the presence of tomato plants and chitin. Annotations using the Blast2GO suite identified 85 of the 257 transcripts whose probe sets afforded up-regulated expression in response to tomato plants. Some of these transcripts were predicted to encode proteins related to Trichoderma-host (fungus or plant) associations, such as Sm1/Elp1 protein, proteases P6281 and PRA1, enchochitinase CHIT42, or QID74 protein, although previously uncharacterized genes were also identified, including those responsible for the possible biosynthesis of nitric oxide, xenobiotic detoxification, mycelium development, or those related to the formation of infection structures in plant tissues.

Conclusion
The effectiveness of the Trichoderma HDO microarray to detect different gene responses under different growth conditions in the fungus T. harzianum strongly indicates that this tool should be useful for further assays that include different stages of plant colonization, as well as for expression studies in other Trichoderma spp. represented on it. Using this microarray, we have been able to define a number of genes probably involved in the transcriptional response of T. harzianum within the first hours of contact with tomato plant roots, which may provide new insights into the mechanisms and roles of this fungus in the Trichoderma-plant interaction.