bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial-to-Mesenchymal Transition and Oncogenic Ras Expression in Resistance to the Protein Kinase Cβ Inhibitor Enzastaurin in Colon Cancer Cells
Authors: Serova Maria , Astorgues-Xerri Lucile , Bieche Ivan , Albert Sebastien , Vidaud Michel , Benhadji Karim A. , Emami Shahin , Vidaud Dominique , Hammel Pascal , Theou-Anton Nathalie , Gespach Christian , Faivre Sandrine , Raymond Eric 
Published: April 2010

Abstract
Identifying molecular factors of sensitivity and resistance of cancer cells to enzastaurin, a drug inhibiting protein kinase C (PKC) β, remains a major challenge to improve its clinical development. Investigating the cellular effects of enzastaurin in a panel of 20 human cancer cell lines, we found that most cells displaying oncogenic K-Ras mutations also display resistance to enzastaurin. Wild-type (WT) K-Ras cancer cells displaying high sensitivity to enzastaurin also expressed high mRNA levels of epithelial markers, such as E-cadherin (CDH1), and low mRNA expressions of mesenchymal markers, such as vimentin, N-cadherin (CDH2), and other genes frequently expressed in mesenchymal transition such as ZEB1, TWIST, SLUG, SNAIL, and TGFβ. WT K-Ras enzastaurin-resistant cells also expressed high levels of mesenchymal markers. Based on this observation, the effects of enzastaurin were investigated in epithelial colon COLO205-S cells that expressed WT Ras/Raf and its derived COLO205-R mesenchymal counterpart selected for resistance to most PKC modulators and displaying oncogenic K-Ras (G13D/exon 2). In COLO205-S cells, inhibition of phosphorylated PKCβ led to the inactivation of AKT and glycogen synthase kinase 3β and was associated with apoptosis without significant effect on cell cycle progression. In COLO205-R cells, enzastaurin induced mainly necrosis at high concentrations. In COLO205-R cells, a strong activation of extracellular signal-regulated kinase 1/2 possibly due to oncogenic K-Ras was predominantly associated with transcription of potent antiapoptotic genes, such as BCL2, GADD45B, and CDKN1A, as well as the multidrug resistance gene ABCB1. From this study, colon cancer cells undergoing apoptosis under enzastaurin exposure seem to frequently express a WT Ras and an epithelial phenotype. Mol Cancer Ther; 9(5); 1308–17. ©2010 AACR.
Nek6 Mediates Human Cancer Cell Transformation and Is a Potential Cancer Therapeutic Target
Authors: Nassirpour Rounak , Shao Lihua , Flanagan Peter , Abrams Tinya , Jallal Bahija , Smeal Tod , Yin Min-Jean 
Published: April 2010

Abstract
We investigated the role of Nek6, a member of the NIMA-related serine/threonine kinase family, in tumorigenesis. Transcript, protein, and kinase activity levels of Nek6 were highly elevated in the malignant tumors and human cancer cell lines compared with normal tissue and fibroblast cells. Expression of exogenous wild-type Nek6 increased anchorage-independent growth of a variety of human cancer cell lines, whereas overexpression of the kinase-dead Nek6 and RNAi knockdown of endogenous Nek6 suppressed cancer cell transformation and induced apoptosis. Additionally, in in vivo xenograft nude mouse model, knockdown of Nek6 in HeLa cells resulted in reduction of tumor size relative to control siRNA tumors. Most importantly, knocking down endogenous Nek6 levels or exogenous expression of the kinase-dead form did not inhibit cell proliferation, nor did it induce apoptosis in normal fibroblast cells. Taken together, our data indicate a pivotal role for Nek6 in tumorigenesis and establish Nek6 as a potential target for treatment of a variety of human cancers. Mol Cancer Res; 8(5); 717–28. ©2010 AACR.
Targeted Knockdown of SEPT9_v1 Inhibits Tumor Growth and Angiogenesis of Human Prostate Cancer Cells Concomitant with Disruption of Hypoxia-Inducible Factor-1 Pathway
Authors: Amir Sharon , Golan Maya , Mabjeesh Nicola J. 
Published: April 2010

Abstract
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the hypoxic response pathway. We recently identified a novel interaction between HIF-1α and the mammalian septin family member, septin 9 protein, isoform 1 (SEPT9_i1), a protein product of septin 9 transcript variant 1 (SEPT9_v1). Septins are a highly conserved family of GTP-binding cytoskeletal proteins that are implicated in multiple cellular functions, including oncogenesis. SEPT9_i1 binds and stabilizes HIF-1α protein and stimulates HIF-1 transcriptional activity by preventing its RACK1-mediated ubiquitination and degradation. SEPT9_i1–HIF-1 activation promotes tumor growth and angiogenesis. The effect of SEPT9_v1 silencing in prostate cancer cells was studied. SEPT9_v1 stable knockdown was generated in PC-3 cells using a specific shRNA. SEPT9_v1 silencing reduced HIF-1α protein expression and inhibited HIF-1 transcriptional activity. SEPT9_v1 knockdown affected cell morphology, deregulated cell cycle, and decreased migration. The antiproliferative effect of shSEPT9_v1 was abolished in HIF-1α knockout colon cancer cells. In vivo, SEPT9_i1 depletion reduced HIF-1α protein expression, cellular proliferation, tumor growth, and angiogenesis. These results provide new insights and validation for applying SEPT9_v1 as a potential target for antitumor therapy by interrupting the HIF-1 pathway. Mol Cancer Res; 8(5); 643–52. ©2010 AACR.
A Vortex Relocation Scheme for Tropical Cyclone Initialization in Advanced Research WRF
Authors: Hsiao Ling-Feng , Liou Chi-Sann , Yeh Tien-Chiang , Guo Yong-Run , Chen Der-Song , Huang Kang-Ning , Terng Chuen-Teyr , Chen Jen-Her 
Published: April 2010

Abstract
This paper introduces a relocation scheme for tropical cyclone (TC) initialization in the Advanced Research Weather Research and Forecasting (ARW-WRF) model and demonstrates its application to 70 forecasts of Typhoons Sinlaku (2008), Jangmi (2008), and Linfa (2009) for which Taiwan’s Central Weather Bureau (CWB) issued typhoon warnings. An efficient and dynamically consistent TC vortex relocation scheme for the WRF terrain-following mass coordinate has been developed to improve the first guess of the TC analysis, and hence improves the tropical cyclone initialization. The vortex relocation scheme separates the first-guess atmospheric flow into a TC circulation and environmental flow, relocates the TC circulation to its observed location, and adds the relocated TC circulation back to the environmental flow to obtain the updated first guess with a correct TC position. Analysis of these typhoon cases indicates that the relocation procedure moves the typhoon circulation to the observed typhoon position without generating discontinuities or sharp gradients in the first guess.
Numerical experiments with and without the vortex relocation procedure for Typhoons Sinlaku, Jangmi, and Linfa forecasts show that about 67% of the first-guess fields need a vortex relocation to correct typhoon position errors while eliminates the topographical effect. As the vortex relocation effectively removes the typhoon position errors in the analysis, the simulated typhoon tracks are considerably improved for all forecast times, especially in the early periods as large adjustments appeared without the vortex relocation. Comparison of the horizontal and vertical vortex structures shows that large errors in the first-guess fields due to an incorrect typhoon position are eliminated by the vortex relocation scheme and that the analyzed typhoon circulation is stronger and more symmetric without distortions, and better agrees with observations. The result suggests that the main difficulty of objective analysis methods [e.g., three-dimensional variational data assimilation (3DVAR)], in TC analysis comes from poor first-guess fields with incorrect TC positions rather than not enough model resolution or observations. In addition, by computing the eccentricity and correlation of the axes of the initial typhoon circulation, the distorted typhoon circulation caused by the position error without the vortex relocation scheme is demonstrated to be responsible for larger track errors. Therefore, by eliminating the typhoon position error in the first guess that avoids a distorted initial typhoon circulation, the vortex relocation scheme is able to improve the ARW-WRF typhoon initialization and forecasts particularly when using data assimilation update cycling.
Individualizing Care for the Many
Authors: Nardacci Elizabeth A. , Bode Bruce W. , Hirsch Irl B. 
Published: April 2010

Purpose A generation of individuals with diabetes has come of age since the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study, providing demonstrable evidence that optimal glycemic control, achieved early with intensive therapy, yields a durable beneficial effect. Yet realizing the full potential of intensive therapy requires more frequent glucose monitoring and accurate interpretation of data. Because patients typically check no more than 3 or 4 times per day and rarely during the night, glucose variability, including glycemic spikes and asymptomatic hypoglycemia, may be missed. Short-term use of a professional continuous glucose monitoring (CGM) device, worn by patients without access to real-time data, reveals patterns of high and low blood glucose undetectable by self-monitoring of blood glucose (SMBG) alone. Clinicians interpret the continuous profile retrospectively to identify and adjust components of the insulin regimen responsible for nocturnal hypoglycemia, postprandial hyperglycemia, and other glucose excursions. This supplement discusses how professional CGM, used as an adjunct to SMBG, can help patients understand the effects of their behavior on glycemic control and consider the potential utility of diabetes technology in transforming knowledge to action. Conclusion Strategic implementation of professional CGM may improve the time- and cost-effectiveness of diabetes care while advancing more personalized treatment in the course of everyday practice.
Platelet-function analyzer closure times indicate shear stress-induced hemostatic abnormalities in patients with aortic valve stenosis and correlate with perioperative transfusion requirements
Authors: Sucker C. , Zotz RB , Kurt M. , Feindt P. , Litmathe J. 
Published: April 2010

Background: Shear stress-induced hemostatic abnormalities are highly prevalent in patients with aortic valve stenosis. In this study, we determined closure times with a platelet-function analyzer (PFA-100, Dade Behring, Marburg, Germany) in patients admitted for aortic valve replacement to assess the correlation with the severity of aortic valve stenosis, blood loss, perioperative transfusion requirements, and need for re-thoracotomy. Patients and Methods: Fifty consecutive patients (mean age [± SD] 68 ± 9 years) were enrolled. Closure times of epinephrin/collagen and adenosine diphosphate (ADP)/collagen cartridges were determined at least ten days after discontinuation of antiplatelet medication and compared to those of healthy control subjects without medication. Results: Closure times of epinephrin/collagen (210 ± 69 sec vs. 140 ± 50 sec, p < 0.0001) and ADP/collagen (145 ± 58 sec vs. 108 ± 45 sec, p < 0.0001) cartridges were prolonged in patients with aortic valve stenosis. Intraoperative transfusion of red blood cell units was associated with the closure times of epinephrin/collagen (r = 0.28, p = 0.04) and ADP/ collagen cartridges (r = 0.28, p = 0.04). Total transfusion of red blood cell units was associated with ADP/ collagen closure times (r = 0.31, p = 0.02), but not epinephrin/collagen closure times (r = 0.26, p = 0.07). No significant association of closure times with intraoperative, postoperative and total transfusion of fresh frozen plasma units was observed. Conclusions: Prolongation of closure times determined with a platelet-function analyzer is highly prevalent in patients with aortic valve stenosis and appears to reflect shear stress-induced hemostatic abnormalities. Since prolonged closure times are associated with increased perioperative transfusion of red blood cell units, the assay could significantly contribute to the identification of individuals at risk.
Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951
Authors: De Moerloose Barbara , Suciu Stefan , Bertrand Yves , Mazingue Françoise , Robert Alain , Uyttebroeck Anne , Yakouben Karima , Ferster Alice , Margueritte Geneviève , Lutz Patrick , Munzer Martine , Sirvent Nicolas , Norton Lucilia , Boutard Patrick , Plantaz Dominique , Millot Frederic , Philippet Pierre , Baila Liliana , Benoit Yves , Otten Jacques ,   for the Children's Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer (EORTC)
Published: April 2010

AbstractThe European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m2/d), 201 to DEX (6 mg/m2/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster–based protocols, pulses should become a standard component of therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728.
Human NLRP3 inflammasome activation is Nox1-4 independent
Authors: van Bruggen Robin , Köker M. Yavuz , Jansen Machiel , van Houdt Michel , Roos Dirk , Kuijpers Taco W. , van den Berg Timo K. 
Published: April 2010

Abstract
The NLRP3 inflammasome can be activated by pathogen-associated molecular patterns or endogenous danger-associated molecular patterns. The activation of the NLRP3 inflammasome results in proteolytic activation and secretion of cytokines of the interleukin-1 (IL-1) family. The precise mode of activation of the NLRP3 inflammasome is still elusive, but has been postulated to be mediated by reactive oxygen species (ROS) generated by an NADPH oxidase. Using primary cells from chronic granulomatous disease (CGD) patients lacking expression of p22phox, a protein that is required for the function of Nox1-4, we show that cells lacking NADPH oxidase activity are capable of secreting normal amounts of IL-1β. Thus, we provide evidence that activation of the NLRP3 inflammasome does not depend on ROS generated from an NADPH oxidase.
Showing their true colors: a practical approach to volume rendering from serial sections
Authors: Handschuh Stephan , Schwaha Thomas , Metscher Brian D 
Published: April 2010

Abstract
Background
In comparison to more modern imaging methods, conventional light microscopy still offers a range of substantial advantages with regard to contrast options, accessible specimen size, and resolution. Currently, tomographic image data in particular is most commonly visualized in three dimensions using volume rendering. To date, this method has only very rarely been applied to image stacks taken from serial sections, whereas surface rendering is still the most prevalent method for presenting such data sets three-dimensionally. The aim of this study was to develop standard protocols for volume rendering of image stacks of serial sections, while retaining the benefits of light microscopy such as resolution and color information.

Results
Here we provide a set of protocols for acquiring high-resolution 3D images of diverse microscopic samples through volume rendering based on serial light microscopical sections using the 3D reconstruction software Amira (Visage Imaging Inc.). We overcome several technical obstacles and show that these renderings are comparable in quality and resolution to 3D visualizations using other methods. This practical approach for visualizing 3D micro-morphology in full color takes advantage of both the sub-micron resolution of light microscopy and the specificity of histological stains, by combining conventional histological sectioning techniques, digital image acquisition, three-dimensional image filtering, and 3D image manipulation and visualization technologies.

Conclusions
We show that this method can yield "true"-colored high-resolution 3D views of tissues as well as cellular and sub-cellular structures and thus represents a powerful tool for morphological, developmental, and comparative investigations. We conclude that the presented approach fills an important gap in the field of micro-anatomical 3D imaging and visualization methods by combining histological resolution and differentiation of details with 3D rendering of whole tissue samples. We demonstrate the method on selected invertebrate and vertebrate specimens, and propose that reinvestigation of historical serial section material may be regarded as a special benefit.
Large genomic differences between the morphologically indistinguishable diplomonads Spironucleus barkhanus and Spironucleus salmonicida
Authors: Roxström-Lindquist Katarina , Jerlström-Hultqvist Jon , Jørgensen Anders , Troell Karin , Svärd Staffan G , Andersson Jan O 
Published: April 2010

Abstract

Background
Microbial eukaryotes show large variations in genome structure and content between lineages, indicating extensive flexibility over evolutionary timescales. Here we address the tempo and mode of such changes within diplomonads, flagellated protists with two nuclei found in oxygen-poor environments. Approximately 5,000 expressed sequence tag (EST) sequences were generated from the fish commensal Spironucleus barkhanus and compared to sequences from the morphologically indistinguishable fish parasite Spironucleus salmonicida, and other diplomonads. The ESTs were complemented with sequence variation studies in selected genes and genome size determinations.

Results
Many genes detected in S. barkhanus and S. salmonicida are absent in the human parasite Giardia intestinalis, the most intensively studied diplomonad. For example, these fish diplomonads show an extended metabolic repertoire and are able to incorporate selenocysteine into proteins. The codon usage is altered in S. barkhanus compared to S. salmonicida. Sequence variations were found between individual S. barkhanus ESTs for many, but not all, protein coding genes. Conversely, no allelic variation was found in a previous genome survey of S. salmonicida. This difference was confirmed by sequencing of genomic DNA. Up to five alleles were identified for the cloned S. barkhanus genes, and at least nineteen highly expressed S. barkhanus genes are represented by more than four alleles in the EST dataset. This could be explained by the presence of a non-clonal S. barkhanus population in the culture, by a ploidy above four, or by duplications of parts of the genome. Indeed, genome size estimations using flow cytometry indicated similar haploid genome sizes in S. salmonicida and G. intestinalis (~12 Mb), whereas the S. barkhanus genome is larger (~18 Mb).

Conclusions
This study indicates extensive divergent genome evolution within diplomonads. Genomic traits such as codon usage, frequency of allelic sequence variation, and genome size have changed considerably between S. barkhanus and S. salmonicida. These observations suggest that large genomic differences may accumulate in morphologically indistinguishable eukaryotic microbes.
Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages
Authors: Cheng Bi-Hua , Liu Yunlong , Xuei Xiaoling , Liao Chung-Ping , Lu Debao , Lasbury Mark E , Durant Pamela J , Lee Chao-Hung 
Published: April 2010

AbstractBackgroundPneumocystispneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance ofPneumocystisorganisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased inPneumocystisinfected hosts. To understand howPneumocystisinactivates alveolar macrophages, Affymetrix GeneChip®RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected andPneumocystis carinii-infected Sprague-Dawley rats.ResultsAnalyses of genes that were affected byPneumocystisinfection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to developPneumocystisinfection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. DuringPneumocystispneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated byPneumocystisinfection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam, Cidea, and Pkib with fold changes ranging between -4.24 and -2.25.ConclusionsIn order to survive in the host,Pneumocystisorganisms change the expression profile of alveolar macrophages. Results of this study revealed thatPneumocystisinfection affects many cellular functions leading to reduced number and activity of alveolar macrophages duringPneumocystispneumonia.