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  1. Article ; Online: Proteomic analysis discovers the differential expression of novel proteins and phosphoproteins in meningioma including NEK9, HK2 and SET and deregulation of RNA metabolismResearch in context

    Jemma Dunn / Sara Ferluga / Vikram Sharma / Matthias Futschik / David A. Hilton / Claire L. Adams / Edwin Lasonder / C. Oliver Hanemann

    EBioMedicine, Vol 40, Iss , Pp 77-

    2019  Volume 91

    Abstract: Background: Meningioma is the most frequent primary intracranial tumour. Surgical resection remains the main therapeutic option as pharmacological intervention is hampered by poor knowledge of their proteomic signature. There is an urgent need to ... ...

    Abstract Background: Meningioma is the most frequent primary intracranial tumour. Surgical resection remains the main therapeutic option as pharmacological intervention is hampered by poor knowledge of their proteomic signature. There is an urgent need to identify new therapeutic targets and biomarkers of meningioma. Methods: We performed proteomic profiling of grade I, II and III frozen meningioma specimens and three normal healthy human meninges using LC-MS/MS to analyse global proteins, enriched phosphoproteins and phosphopeptides. Differential expression and functional annotation of proteins was completed using Perseus, IPA® and DAVID. We validated differential expression of proteins and phosphoproteins by Western blot on a meningioma validation set and by immunohistochemistry. Findings: We quantified 3888 proteins and 3074 phosphoproteins across all meningioma grades and normal meninges. Bioinformatics analysis revealed commonly upregulated proteins and phosphoproteins to be enriched in Gene Ontology terms associated with RNA metabolism. Validation studies confirmed significant overexpression of proteins such as EGFR and CKAP4 across all grades, as well as the aberrant activation of the downstream PI3K/AKT pathway, which seems differential between grades. Further, we validated upregulation of the total and activated phosphorylated form of the NIMA-related kinase, NEK9, involved in mitotic progression. Novel proteins identified and validated in meningioma included the nuclear proto-oncogene SET, the splicing factor SF2/ASF and the higher-grade specific protein, HK2, involved in cellular metabolism. Interpretation: Overall, we generated a proteomic thesaurus of meningiomas for the identification of potential biomarkers and therapeutic targets. Fund: This study was supported by Brain Tumour Research. Keywords: Meningioma, Proteomics, Phosphoproteins, Differential expression, Grade-specific, RNA metabolism
    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Transcriptional Profiling of the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells (HUVECs)

    Gürkan Bal / Julian Kamhieh-Milz / Matthias Futschik / Thomas Häupl / Abdulgabar Salama / Anja Moldenhauer

    Cell Transplantation, Vol

    2012  Volume 21

    Abstract: Endothelial cells can be successfully used to maintain or increase the number of hematopoietic stem cells in vitro. Previously we identified hematopoietic progenitor cell (HPC) expansion or survival benefit induced by IL-1β-, IL-3-, and IL-6-stimulated ... ...

    Abstract Endothelial cells can be successfully used to maintain or increase the number of hematopoietic stem cells in vitro. Previously we identified hematopoietic progenitor cell (HPC) expansion or survival benefit induced by IL-1β-, IL-3-, and IL-6-stimulated human umbilical vein endothelial cell (HUVEC) supernatants. In order to identify molecular mechanisms that support hematopoiesis, we examined the time-dependent expression profiles of IL-1β-, IL-3-, and IL-6-stimulated HUVECs via microarray. Here, we present 24 common upregulated elements and three common downregulated elements of IL-1β- and IL-3-stimulated HUVECs, with these factors exhibiting great potential for the observed HPC expansion. Furthermore, metabolic pathway analysis resulted in the identification of nonproteinogenic factors such as prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and determined their HPC expansion potential via delta, methylcellulose, and cobblestone assays. We confirmed PGE 2 and spermine as hematopoietic expansion factors. Furthermore, we identified several factors such as SSAT, extracellular matrix components, microRNA21, and a microvesicle-mediated cross-talk between the endothelium and HPCs that may play a crucial role in determining stem cell fate. Our results suggest that microarray in combination with functional annotations is a convenient method to identify novel factors with great impact on HPC proliferation and differentiation.
    Keywords Medicine ; R
    Subject code 570
    Language English
    Publishing date 2012-02-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Short RNA half-lives in the slow-growing marine cyanobacterium Prochlorococcus

    Steglich, Claudia / Debbie Lindell / Matthias Futschik / Robert Steen / Sallie W Chisholm / Trent Rector

    Genome biology. 2010 May, v. 11, no. 5

    2010  

    Abstract: BACKGROUND: RNA turnover plays an important role in the gene regulation of microorganisms and influences their speed of acclimation to environmental changes. We investigated whole-genome RNA stability of Prochlorococcus, a relatively slow-growing marine ... ...

    Abstract BACKGROUND: RNA turnover plays an important role in the gene regulation of microorganisms and influences their speed of acclimation to environmental changes. We investigated whole-genome RNA stability of Prochlorococcus, a relatively slow-growing marine cyanobacterium doubling approximately once a day, which is extremely abundant in the oceans. RESULTS: Using a combination of microarrays, quantitative RT-PCR and a new fitting method for determining RNA decay rates, we found a median half-life of 2.4 minutes and a median decay rate of 2.6 minutes for expressed genes - twofold faster than that reported for any organism. The shortest transcript half-life (33 seconds) was for a gene of unknown function, while some of the longest (approximately 18 minutes) were for genes with high transcript levels. Genes organized in operons displayed intriguing mRNA decay patterns, such as increased stability, and delayed onset of decay with greater distance from the transcriptional start site. The same phenomenon was observed on a single probe resolution for genes greater than 2 kb. CONCLUSIONS: We hypothesize that the fast turnover relative to the slow generation time in Prochlorococcus may enable a swift response to environmental changes through rapid recycling of nucleotides, which could be advantageous in nutrient poor oceans. Our growing understanding of RNA half-lives will help us interpret the growing bank of metatranscriptomic studies of wild populations of Prochlorococcus. The surprisingly complex decay patterns of large transcripts reported here, and the method developed to describe them, will open new avenues for the investigation and understanding of RNA decay for all organisms.
    Keywords acclimation ; gene expression ; half life ; messenger RNA ; microarray technology ; microorganisms ; nucleotides ; oceans ; operon ; Prochlorococcus ; reverse transcriptase polymerase chain reaction ; transcription (genetics)
    Language English
    Dates of publication 2010-05
    Size p. 2347.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2010-11-5-r54
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Differentially Expressed MicroRNAs in Maternal Plasma for the Noninvasive Prenatal Diagnosis of Down Syndrome (Trisomy 21)

    Julian Kamhieh-Milz / Reham Fadl Hassan Moftah / Gürkan Bal / Matthias Futschik / Viktor Sterzer / Omid Khorramshahi / Martin Burow / Gundula Thiel / Annegret Stuke-Sontheimer / Rabih Chaoui / Sundrela Kamhieh-Milz / Abdulgabar Salama

    BioMed Research International, Vol

    2014  Volume 2014

    Abstract: Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be ... ...

    Abstract Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS.
    Keywords Medicine ; R
    Subject code 500 ; 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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