13 research outputs found

    IN THE EYE OF THE PUBLIC: MILITARY–MEDIA RELATIONS IN SOUTH AFRICA

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    School for Security and Africa Studies: Political Science (Mil

    Measurements in wound healing : effects of topical agents on full thickness dermal incised wounds in an animal model

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    Bibliography: leaves 55-59.Inert topical agents in the form of creams, lotions and ointments are often applied to wounds to create an environment conducive to wound healing. These agents, although not pharmacologically active on the intact skin, have activity when applied to wounds where the stratum comeum barrier to penetration is absent. From measurements of simple parameters like the rate of re-epitheliasation. it is known that some topical agents enhance wound healing while others retard the healing process. There is data available on the antiseptic and anti-microbial properties of most of the topical agents in use today, but ail the effects of these products on the micro-environment of wounds and their influence on the process of healing is not known. Central to the study of wounds and wound healing is the need for accurate methods to evaluate wounds. Parameters used for measuring outcome should be unambiguous and measurements should be accurate and reproducible. At present, no universally accepted methods of assessing wounds exist. Clinical evaluation is usually subjective and not quantitative, resulting in unacceptable levels of inter- and intra-observer variation. Similarly lacking are clear histological correlates of what we consider good healing characteristics of a wound. As our knowledge increase about the complex process of wound healing, in particular the hormones and peptide growth factors that regulate the process, possibilities arise for therapeutic intervention to enhance or improve clinical outcome. At the same time, the need for objective measurements becomes more urgent, as we need to evaluate and compare treatment options. Previous measurement systems were developed, ranging from visual scoring systems to measurement of biological and chemical wound constituents. Physical characteristics of healing wounds can also be measured by properties such as the tensile strength. The structural and ultra- structural elements of healing wounds remain difficult to measure, although immuno-histochemistry and scanning electron microscopy allows some quantification and simple morphometric measurements. With current advances in computer technology however, rapid, automatic measurements can be made from tissue sections for a variety of practical applications in the pathology laboratory. Image analysis offers dynamic functional imaging, linking multiple data sources to provide composite quantitative systems. Further correlation of detailed histologic examination of wounds to a detailed clinical assessment of the same wounds is important, not only to add credibility to clinical scoring schemes, but also to understand which structural features of the dermis are important for the severity of scarring (and therefore which should be the object of future therapeutic or preventative strategies)

    MagiCMicroRna: a web implementation of AgiMicroRna using shiny

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    BACKGROUND: MicroRNA expression can be quantified using sequencing techniques or commercial microRNA-expression arrays. Recently, the AgiMicroRna R-package was published that enabled systematic preprocessing and statistical analysis for Agilent microRNA arrays. Here we describe MagiCMicroRna, which is a user-friendly web interface for this package, together with a new filtering approach. RESULTS: We used MagiCMicroRna to normalize and filter an Agilent miRNA microarray dataset of cancerous and normal tissues from 14 different patients. With the standard filtering procedure, 250 out of 817 microRNAs remained, whereas the new group-specific filtering approach resulted in broader datasets for further analysis in most groups (>279 microRNAs remaining). CONCLUSIONS: The user-friendly web interface of MagiCMicroRna enables researchers to normalize and filter Agilent microarrays by the click of one button. Furthermore, MagiCMicroRna provides flexibility in choosing the filtering method. The new group-specific filtering approach lead to an increased number and additional tissue-specific microRNAs remaining for subsequent analysis compared to the standard procedure. The MagiCMicroRna web interface and source code can be downloaded from https://bitbucket.org/mutgx/magicmicrorna.git. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-015-0035-5) contains supplementary material, which is available to authorized users

    Dynamic Interplay between the Transcriptome and Methylome in Response to Oxidative and Alkylating Stress

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    In recent years, it has been shown that free radicals not only react directly with DNA but also regulate epigenetic processes such as DNA methylation, which may be relevant within the context of, for example, tumorigenesis. However, how these free radicals impact the epigenome remains unclear. We therefore investigated whether methyl and hydroxyl radicals, formed by <i>tert</i>-butyl hydroperoxide (TBH), change temporal DNA methylation patterns and how this interferes with genome-wide gene expression. At three time points, TBH-induced radicals in HepG2 cells were identified by electron spin resonance spectroscopy. Total 5-methylcytosine (5mC) levels were determined by liquid chromatography and tandem mass spectrometry and genome-wide changes in 5mC and gene expression by microarrays. Induced methylome changes rather represent an adaptive response to the oxidative stress-related reactions observed in the transcriptome. More specifically, we found that methyl radicals did not induce DNA methylation directly. An initial oxidative and alkylating stress-related response of the transcriptome during the early phase of TBH treatment was followed by an epigenetic response associated with cell survival signaling. Also, we identified genes of which the expression seems directly regulated by DNA methylation. This work suggests an important role of the methylome in counter-regulating primary oxidative and alkylating stress responses in the transcriptome to restore normal cell function. Altogether, the methylome may play an important role in counter-regulating primary oxidative and alkylating stress responses in the transcriptome presumably to restore normal cell function

    Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma

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    Chronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with hepatocellular carcinoma (HCC) development. AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental exposures, such as AFB1, may create a persistent epigenetic footprint. Deregulation of epigenetic mechanisms has actually been reported in HCC patients following AFB1 exposure; however, no attempts have yet been made to investigate early effects on the epigenome level which may be persistent on longer term, thereby possibly initiating carcinogenic events. In this study, we aim to identify methyl DNA-mRNA-interactions representative for a persistent epigenetic footprint associated with the early onset of AFB1-induced HCC. For this, primary human hepatocytes were exposed to 0.3 mu M of AFB1 for 5 days. Persistent epigenetic effects were measured 3 days after terminating the carcinogenic exposure. Whole genome DNA methylation changes and whole genome transcriptomic analysis were analyzed applying microarray technologies, and cross-omits interactions were evaluated. Upon combining transcriptomics data with results on DNA methylation, a range of persistent hyper- and hypo-methylated genes was identified which also appeared affected on the transcriptome level. For six of the hypo-methylated and up-regulated genes, namely TXNRDI, PCNA, CCNK, DIAPH3, RAB27A and HISTIH2BF, a clear role in carcinogenic events could be identified. This study is the first to report on a carcinogen-induced persistent impact on the epigenetic footprint in relation with the transcriptome which could be indicative for the early onset of AFB1-related development of HCC
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