bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes
Authors: Van den Bossche Jan , Bogaert Pieter , van Hengel Jolanda , Guérin Christopher J. , Berx Geert , Movahedi Kiavash , Van den Bergh Rafael , Pereira-Fernandes Anna , Geuns Jan M. C. , Pircher Hanspeter , Dorny Pierre , Grooten Johan , De Baetselier Patrick , Van Ginderachter Jo A. 
Published: September 2009

AbstractAlternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament remains poorly characterized. Here, we established E-cadherin (Cdh1) as a selective marker for IL-4/IL-13–exposed mouse and human macrophages, which is STAT6-dependently induced during polarized Th2 responses associated with Taenia crassiceps helminth infections or allergic airway inflammation. The IL-4–dependent, arginase-1/ornithine decarboxylase–mediated production of polyamines is important for maximal Cdh1 induction, unveiling a novel mechanism for IL-4–dependent gene transcription. At the macrophage surface, E-cadherin forms a functional complex with the catenins that accumulates at sites of cell contact. Macrophage-specific deletion of the Cdh1 gene illustrates the implication of E-cadherin in IL-4–driven macrophage fusion and heterotypic interactions with CD103+ and KLRG1+ T cells. This study identifies the E-cadherin/catenin complex as a discriminative, partly polyamine-regulated feature of IL-4/IL-13–exposed alternatively activated macrophages that contributes to homotypic and heterotypic cellular interactions.
Glycoprotein Ibα inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism
Authors: McEwan Paul A. , Andrews Robert K. , Emsley Jonas 
Published: September 2009

Abstract
Platelet glycoprotein Ibα (GpIbα) interactions with von Willebrand factor (VWF) are a critical early event in platelet adhesion, which contributes to hemostasis and thrombosis. Here we report the structure of a complex between GpIbα and a potent peptide inhibitor. The cyclic peptide (CTERMALHNLC) was isolated from a cysteine-constrained phage display library, and in the complex this forms one and a half turns of an amphipathic α-helix, the curvature of which facilitates contacts with the curved concave face of the GpIbα leucine-rich repeats. The peptide has only limited overlap with the VWF binding site. It effectively inhibits by stabilizing an alternative α-helical conformation of a regulatory loop that forms an extended β-hairpin upon VWF binding. The structure defines a previously unrecognized binding site within GpIbα and represents a clear strategy for developing antiplatelet agents targeting the GpIbα-VWF interaction allosterically.
Allotransplantation in pediatric HL
Authors: Nachman James 
Published: September 2009

Abstract
In this issue of Blood, Claviez and colleagues report on the outcomes of 91 patients younger than 18 years of age who underwent an allogeneic bone marrow transplantation for HL between 1987 and 2005. The outcomes were reported to the European Group for Blood and Marrow Transplantation.1
Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach
Authors: Wang Wenhui , Nunez-Iglesias Juan , Luan Yihui , Sun Fengzhu 
Published: September 2009

AbstractBackgroundMany aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks.ResultsRecent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks.ConclusionOur use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.
Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification
Authors: Ito Tatsuo , Yadav Neelu , Lee Jaeho , Furumatsu Takayuki , Yamashita Satoshi , Yoshida Kenji , Taniguchi Noboru , Hashimoto Megumi , Tsuchiya Megumi , Ozaki Toshifumi , Lotz Martin , Bedford Mark T , Asahara Hiroshi 
Published: September 2009

Abstract

Background
Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9.

Results
CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain in vivo and in vitro. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating Cyclin D1 expression and cell cycle progression of chondrocytes.

Conclusion
These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.
Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes
Authors: Karanth Santhosh , Lall Santosh P , Denovan-Wright Eileen M , Wright Jonathan M 
Published: September 2009

AbstractBackgroundIn the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid), sunflower oil (12% lipid, rich in linoleic acid), linseed oil (12% lipid, rich in linolenic acid), or low fat (4% lipid, low fat diet) for 10 weeks. FA profiles and the steady-state levels offabpmRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined.ResultFA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes,fabp1a/fabp1b.1/fabp1b.2,fabp7a/fabp7b, andfabp11a/fabp11b, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). In brain, the steady-state level offabp7bmRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level offabp1b.1andfabp7bwere elevated in fish fed the linolenic acid-rich diet; in liver, the level offabp7amRNAs was elevated in fish fed the low fat diet; and in muscle, the level offabp7aandfabp11amRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases, induction of the steady-state level offabpmRNAs by dietary FAs correlated with induced levels of hnRNA for a givenfabpgene. As such, up-regulation of the steady-state level offabpmRNAs by FAs occurred at the level of initiation of transcription. None of the sister duplicates of thesefabpgenes exhibited an increase in their steady-state transcript levels in a specific tissue following feeding zebrafish any of the four experimental diets.ConclusionDifferential induction of only one of the sister pair of duplicatedfabpgenes by FAs provides evidence to support the DDC model for retention of duplicated genes in the zebrafish genome by either subfunctionalization or neofunctionalization.
Transcriptional response of the model planctomycete Rhodopirellula baltica SH1T to changing environmental conditions
Authors: Wecker Patricia , Klockow Christine , Ellrott Andreas , Quast Christian , Langhammer Philipp , Harder Jens , Glöckner Frank Oliver 
Published: September 2009

AbstractBackgroundThe marine model organismRhodopirellula balticaSH1Twas the firstPlanctomyceteto have its genome completely sequenced. The genome analysis predicted a complex lifestyle and a variety of genetic opportunities to adapt to the marine environment. Its adaptation to environmental stressors was studied by transcriptional profiling using a whole genome microarray.ResultsStress responses to salinity and temperature shifts were monitored in time series experiments. Chemostat cultures grown in mineral medium at 28°C were compared to cultures that were shifted to either elevated (37°C) or reduced (6°C) temperatures as well as high salinity (59.5‰) and observed over 300 min. Heat shock showed the induction of several known chaperone genes. Cold shock altered the expression of genes in lipid metabolism and stress proteins. High salinity resulted in the modulation of genes coding for compatible solutes, ion transporters and morphology. In summary, over 3000 of the 7325 genes were affected by temperature and/or salinity changes.ConclusionTranscriptional profiling confirmed thatR. balticais highly responsive to its environment. The distinct responses identified here have provided new insights into the complex adaptation machinery of this environmentally relevant marine bacterium. Our transcriptome study and previous proteome data suggest a set of genes of unknown functions that are most probably involved in the global stress response. This work lays the foundation for further bioinformatic and genetic studies which will lead to a comprehensive understanding of the biology of a marinePlanctomycete.
Transcriptome and proteome analyses of adaptive responses to methyl methanesulfonate in Escherichia coli K-12 and ada mutant strains
Authors: Baek Jong Hwan , Han Mee-Jung , Lee Sang Yup , Yoo Jong-Shin 
Published: September 2009

AbstractBackgroundThe Ada-dependent adaptive response system inEscherichia coliis important for increasing resistance to alkylation damage. However, the global transcriptional and translational changes during this response have not been reported. Here we present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS) inE. coliW3110 and itsadamutant strains.ResultsTranscriptome profiling showed that 1138 and 2177 genes were differentially expressed in response to MMS treatment in the wild-type and mutant strains, respectively. A total of 81 protein spots representing 76 nonredundant proteins differentially expressed were identified using 2-DE and LC-MS/MS. In the wild-type strain, many genes were differentially expressed upon long-exposure to MMS, due to both adaptive responses and stationary phase responses. In theadamutant strain, the genes involved in DNA replication, recombination, modification and repair were up-regulated 0.5 h after MMS treatment, indicating its connection to the SOS and other DNA repair systems. Interestingly, expression of the genes involved in flagellar biosynthesis, chemotaxis, and two-component regulatory systems related to drug or antibiotic resistance, was found to be controlled by Ada.ConclusionThese results show in detail the regulatory components and pathways controlling adaptive response and how the related genes including the Ada regulon are expressed with this response.
Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's disease
Authors: Faust Katharina , Gehrke Stephan , Yang Yufeng , Yang Lichuan , Beal M Flint , Lu Bingwei 
Published: September 2009

AbstractBackgroundParkinson's disease (PD) is the most common movement disorder. Extrapyramidal motor symptoms stem from the degeneration of the dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Although the cause of PD remains unknown, several pathogenic factors have been identified, which cause dopaminergic neuron (DN) death in the substantia nigra (SN). These include oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity. Manipulation of these factors may allow the development of disease-modifying treatment strategies to slow neuronal death. Inhibition of DJ-1A, theDrosophilahomologue of the familial PD gene DJ-1, leads to oxidative stress, mitochondrial dysfunction, and DN loss, making fly DJ-1A model an excellentin vivosystem to test for compounds with therapeutic potential.ResultsIn the present study, aDrosophilaDJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection inDrosophilaDJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level.ConclusionThe present study further validatesDrosophilaas a valuable model for preclinical testing of drugs with therapeutic potential for neurodegenerative diseases. The lower cost and amenability to high throughput testing makeDrosophilaPD models effectivein vivotools for screening novel therapeutic compounds. If our findings can be further validated in mammalian PD models, they would implicate drugs combining antioxidant and anti-inflammatory properties as strong therapeutic candidates for mechanism-based PD treatment.
A MANBAmutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant
Authors: Sabourdy Frédérique , Labauge Pierre , Stensland Hilde Monica Frostad Riise , Nieto Michèle , Garcés Violeta Latorre , Renard Dimitri , Castelnovo Giovanni , de Champfleur Nicolas , Levade Thierry 
Published: September 2009

AbstractBackgroundβ-Mannosidosis (OMIM 248510) is a rare inborn lysosomal storage disorder caused by the deficient activity of β-mannosidase, an enzyme encoded by a single gene (MANBA) located on chromosome 4q22-25. To date, only 20 cases of this autosomal recessive disorder have been described and 14 differentMANBAmutations were incriminated in the disease. These are all null mutations or missense mutations that abolish β-mannosidase activity. In this study, we characterized the molecular defect of a new case of β-mannosidosis, presenting with a severe neurological disorder.MethodsGenomic DNA was isolated from peripheral blood leukocytes of the patient to allowMANBAsequencing. The identified mutation was engineered by site-directed mutagenesis and the mutant protein was expressed through transient transfection in HEK293T cells. The β-mannosidase expression and activity were respectively assessed by Western blot and fluorometric assay in both leukocytes and HEK293T cells.ResultsA missense disease-associated mutation, c.1922G>A (p.Arg641His), was identified for which the patient was homozygous. In contrast to previously described missense mutations, this substitution does not totally abrogate the enzyme activity but led to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression studies in transfected cells also resulted in 7% residual activity.ConclusionCorrelations between MANBA mutations, residual activity of β-mannosidase and the severity of the ensuing neurological disorder are discussed. Whether the c.1922G>A mutation is responsible for a yet undescribed pseudodeficiency of β-mannosidase is also discussed.
RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study
Authors: Beier Christoph P , Schmid Christina , Gorlia Thierry , Kleinletzenberger Christine , Beier Dagmar , Grauer Oliver , Steinbrecher Andreas , Hirschmann Birgit , Brawanski Alexander , Dietmaier Christopher , Jauch-Worley Tanja , Kölbl Oliver , Pietsch Torsten , Proescholdt Martin , Rümmele Petra , Muigg Armin , Stockhammer Günther , Hegi Monika , Bogdahn Ulrich , Hau Peter 
Published: September 2009

Abstract

Background
Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for.

Methods
In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression.

Results
The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison.

Conclusion
Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data

Trial registration
clinicaltrials.gov NCT00944801.
A protein-based set of reference markers for liver tissues and hepatocellular carcinoma
Authors: Sun Stella , Yi Xin , Poon Ronnie TP , Yeung Chun , Day Philip JR , Luk John M 
Published: September 2009

Abstract

Background
During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify "housekeeping" markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression.

Methods
A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers.

Results
The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples.

Conclusion
Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference moieties for normalisation of gene and protein expression in clinical research employing human hepatic tissues.
Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer
Authors: Wei Na , Liu Stephanie S , Leung Thomas HY , Tam Kar F , Liao Xiao Y , Cheung Annie NY , Chan Karen KL , Ngan Hextan YS 
Published: September 2009

AbstractBackgroundProgrammed cell death 4 (Pdcd4) is a novel tumour suppressor and originally identified as a neoplastic transformation inhibitor. The aim of this study was to investigate the expression, prognostic significance and potential function of Pdcd4 in ovarian cancer.ResultsThe expression of Pdcd4 was examined in 30 normal ovarian tissues, 16 borderline and 93 malignant ovarian tissues. A continuous down regulation of Pdcd4 expression in the sequence of normal, borderline and malignant tissues was observed. The expressions of Pdcd4 in both ovarian borderline tissues and carcinomas were significantly lower than the expression in normal ovarian tissues (p < 0.001). Furthermore, patients with lower Pdcd4 expressions were found to have shorter disease-free survival (p = 0.037). The expression of Pdcd4 was also assessed by immunohistochemical analysis in 13 ovarian normal tissues and 44 carcinomas. Different subcellular localization of Pdcd4 was observed in normal compared to malignant cells. Predominant nuclear localization of Pdcd4 was found in normal ovarian tissues while ovarian carcinomas showed mainly cytoplasmic localization of Pdcd4.ConclusionOur study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients.