122 research outputs found

    Differential Gene Expression Analysis and Clinical Correlations within Endemic Burkitt Lymphoma

    Get PDF
    Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in equatorial Africa and is associated with malaria and Epstein-Barr virus co-infections. Molecular alterations within the eBL tumor genome and transcriptome have not been adequately investigated or compared to sporadic Burkitt lymphoma (sBL). Given that eBL has distinct clinical presentations in the jaw as opposed to the abdomen which are associated with survival, we hypothesize that transcriptome sequencing (RNA-seq) and potentially underlying genetic alterations will enhance our understanding of pathogenesis. Our results compare genome-wide RNA transcript abundances between eBL tumors from children (ages 6-7 yrs) with Stage I (Jaw tumor, n=14) and Stage II (abdominal, n=24) disease from Western Kenya to previously published work analyzing sBL which present in older children residing in developed countries and that tend not to be associated with EBV. Our initial analysis confirms mutational changes with likely functional alterations in the genes ID3 and TCF3, the key regulators of oncogenic pathways implicated in BL. However, the specific mutations observed in sBL are at lower frequency within eBL cases. This work represents the first comprehensive gene expression profile analysis of different eBL tumors. Hierarchical clustering, gene ontology and pathway analysis will provide insight into pathogenesis and new targets for chemotherapy

    Integrative microRNA and mRNA deep-sequencing expression profiling in endemic Burkitt lymphoma

    Get PDF
    BACKGROUND: Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence suggest that abnormal modulation of mRNA transcription via miRNAs might be a significant factor in lymphomagenesis. However, the alterations in these miRNAs and their correlations to their putative mRNA targets have not been extensively studied relative to normal germinal center (GC) B cells. METHODS: Using more sensitive and specific transcriptome deep sequencing, we compared previously published small miRNA and long mRNA of a set of GC B cells and eBL tumors. MiRWalk2.0 was used to identify the validated target genes for the deregulated miRNAs, which would be important for understanding the regulatory networks associated with eBL development. RESULTS: We found 211 differentially expressed (DE) genes (79 upregulated and 132 downregulated) and 49 DE miRNAs (22 up-regulated and 27 down-regulated). Gene Set enrichment analysis identified the enrichment of a set of MYC regulated genes. Network propagation-based method and correlated miRNA-mRNA expression analysis identified dysregulated miRNAs, including miR-17~95 cluster members and their target genes, which have diverse oncogenic properties to be critical to eBL lymphomagenesis. Central to all these findings, we observed the downregulation of ATM and NLK genes, which represent important regulators in response to DNA damage in eBL tumor cells. These tumor suppressors were targeted by multiple upregulated miRNAs (miR-19b-3p, miR-26a-5p, miR-30b-5p, miR-92a-5p and miR-27b-3p) which could account for their aberrant expression in eBL. CONCLUSION: Combined loss of p53 induction and function due to miRNA-mediated regulation of ATM and NLK, together with the upregulation of TFAP4, may be a central role for human miRNAs in eBL oncogenesis. This facilitates survival of eBL tumor cells with the IGH/MYC chromosomal translocation and promotes MYC-induced cell cycle progression, initiating eBL lymphomagenesis. This characterization of miRNA-mRNA interactions in eBL relative to GC B cells provides new insights on miRNA-mediated transcript regulation in eBL, which are potentially useful for new improved therapeutic strategies

    Cooperation between Russian research organizations and industrial companies: factors and problems

    Get PDF
    The study is focused on the cooperation of Russian companies with research organizations in implementing R&D projects during technological innovation. Taking into account behavioral changes, authors carry out a micro-level analysis based on empirical data of executive survey of over 600 Russian industrial firms (2011—2012) and about 350 research organizations and universities (2012). The authors emphasize the key factors of firms’ demand for outsourcing R&D reveal the main barriers to the development of university-industry cooperation and their particularities for different cooperation actors. The analysis shows that there is a positive relation between the size of a company and R&D outsourcing. As for the factor of age, the highest cooperation activity of Russian firms is observed among enterprises founded over 20 years ago. As far as concernes cooperation activity of research organizations, large ones are significantly more likely to cooperate with business. A common prerequisite for research organizations' R&D cooperation with business is sufficient academic ranking. Business and science evaluate differently various obstacles to effective cooperation. For firms, the main problems are the inflated costs of national R&Ds, insufficient research organizations’ orientation at company needs, and low quality of developments. As for representatives of research organizations, they mention as barriers primarily the lack of companies' receptivity to innovation and inadequate information about promising developments. Businesses are more optimistic about cooperation with science if they already have a relevant experience of interaction. In the case of research organizations we observe a different pattern: most problems seem more significant to organizations conducting R&D in business interests

    The Earth: Plasma Sources, Losses, and Transport Processes

    Get PDF
    This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed
    • …
    corecore