18 research outputs found

    DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

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    Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas

    Effects of the invasive annual grass Lolium multiflorum Lam. on the growth and physiology of a Southern African Mediterranean-climate geophyte Tritonia crocata (L.) Ker. Gawl. under different resource conditions

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    Thesis (M. Environmental Science (Ecological Remediation and Sustainable Utilisation))--North-West University, Potchefstroom Campus, 2008.Little is known of the physiological and biochemical mechanisms underlying competitive interactions between alien invasive grasses and native taxa, and how these are affected by resource supply. Consequently, this study compared photosystem II (PS II) function, photosynthetic gas and water exchange, enzyme and pigment concentrations, flowering and biomass accumulation in an indigenous geophyte, Tritonia crocata (L.) Ker. Gawl., grown in monoculture and admixed with the alien grass, Lolium multiflorum Lam., at different levels of water and nutrient supply. Diminished stomatal conductances were the primary cause of reduced net C02 assimilation rates, and consequent biomass accumulation in T. crocata admixed with L. multiflorum at all levels of water and nutrient supply with one exception. These corresponded with decreased soil water contents induced presumably by more efficient competition for water by L. multiflorum, whose biomass was inversely correlated with soil water content. Biochemical impairments to photosynthesis were also apparent in T. crocata admixed with L. multiflorum at low levels of water and nutrient supply. These included a decline in the density of working photosystems (reaction center per chlorophyll RC/ABS), which corresponded with a decreased leaf chlorophyll a content and a decreased efficiency of conversion of excitation energy to electron transport (Â¥0 / l-^o), pointing to a reduction in electron transport capacity beyond QA~, a decline in apparent carboxylation efficiency and Rubisco content. At low nutrient levels but high water supply, non-stomatal induced biochemical impairments to photosynthesis (decreased RC/ABS, chlorophyll a and Rubisco content) were apparent in T. crocata admixed with L. multiflorum. These attributed to a reallocation of fixed carbohydrate reserves to floral production which increased significantly in T. crocata under these conditions only and associated with a corresponding reduction in the mass of its underground storage organ (bulb). The results of this study did not support the hypothesis that under conditions of low water and low nutrient supply invasive annual grasses would have a lesser impact on the growth and physiology of native geophytes than under resource enriched conditions that favor growth of these grasses. Unresolved is whether resource limitation and allelopathic mechanisms functioned simultaneously in the inhibition of the native geophyte by the alien grass.Master

    Oxidative stress responses in the aquatic macrophyte, Ceratophyllum Demersum L., as biomarkers of metal exposure

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    Thesis (DTech (Environmental Health))--Cape Peninsula University of Technology, 2017.Metal pollution in aquatic environments is considered a major environmental concern because of variation in several abiotic factors that impose severe restrictions on organisms living in these areas. Ceratophyllum demersum L. (family Ceratophyllaceae), a hornwort or coontail, free floating rootless macrophyte has been suggested a suitable model for investigating metal stress and was used in the current study. This study assessed the use of selected biological responses, namely antioxidant responses and changes in chlorophyll concentration in Ceratophyllum demersum L., as biomarkers of metal exposure, and also investigated the field application of these responses in the Diep River. The ultimate aim was also to determine the usefulness of C. demersum as model of metal contamination and as phytoremediator after a pollution event. An investigation of metal bioaccumulation in this macrophyte exposed to different concentrations of a combination of metals over a five-week exposure period in a greenhouse, was undertaken, as well as a field study in the Diep River, Milnerton, Cape Town and a pond (reference site) at the Cape Peninsula University of Technology, Cape Town, to validate experimental results. In the laboratory study the water was contaminated once off at the beginning of the study, to simulate a pollution event. The metal concentrations in the water and plants were measured in the four treatments and the control every week over a five-week exposure period. The samples were acid-digested and analysed with an Inductively-Coupled Plasma-Mass Spectrophotometer (ICP-MS). The results showed that concentrations of the metals in the water varied in all treatments over time with no specific patterns amongst the treatment groups. This macrophyte proved highly effective in the bioaccumulation of these metals at all four exposure concentrations. The metals bioaccumulated rapidly in the plants after the water was spiked. The main focus of the study was to investigate the possible use of biochemical responses in C. demersum as possible biomarkers for metal exposure. A range of antioxidant/oxidative stress parameters were measured in the plant exposed to a combination of metals (Al, Cu, Fe, Zn) in four different treatments over the five week exposure period. Total antioxidant capacity (TAC) was measured using Total Polyphenols (TP), Ferric Reducing Antioxidant Power (FRAP) and Oxygen Radical Absorbance Capacity assay (ORAC), enzyme activity was determined using Catalase (CAT), Superoxide Dismutase (SOD), Ascorbate Acid (AsA) and Total Glutathione (GSHt) and lipid peroxidation was measured by using Thiobarbituric Acid Reactive Substances (TBARS) and Conjugated Dienes (CDs). The cocktail of the four metals induced significant changes in the antioxidant defence system of C. demersum, including the antioxidant enzyme activities. The different metal exposures disturbed the cellular redox status in the plant. The current study has demonstrated that this macrophyte shows tolerance to metal-induced oxidative stress and that it can survive under relatively high concentrations of these metals by adapting its antioxidant defence strategies. Chlorophyll was extracted in 80% chilled acetone in the dark and the absorbance values were determined using a spectrophotometer. Chlorophyll a (chl a), chlorophyll b (chl b) and total chlorophyll (chl t) contents were measured under different exposure concentrations of metals in the macrophyte. The results of this study indicated that chlorophyll contents were variable over the exposure period and no significant differences in chlorophyll concentrations were found between weeks. A field study in the Diep River and the pond located at the CPUT campus (reference site) was conducted to validate experimental results. Plants in a polluted section of the Diep River were shown to bioaccumulate metals to high concentrations. Bioaccumulation of metals in C. demersum might have induced oxidative stress, and other environmental factors such as temperature- and chemical stress might have caused chlorophyll degradation. The chlorophyll concentrations in the plants of the pond (reference site) might also have been affected by temperature and chemical stress of the water. Significantly higher AsA, CAT, ORAC, SOD and TBARS concentrations in the Diep River plants might be an indication that the plants in the river might be well adapted to the constant exposure to metals and that the plants might have developed a tolerance mechanism to cope with oxidative stress compared to those of the pond. The results show that metals are bioaccumulated quickly by C. demersum after the water is contaminated with metals, i.e. after the "pollution event". However, over time, metals are continuously exchanged between the plants and the water, accounting for the fluctuations in metal concentrations observed over time. This study has shown that C. demersum has phytoremediation potential because it was able to remove high concentrations of metals from the contaminated water. Therefore, C. demersum, can be applied as a model for metal contamination and a phytoremediator after a pollution event. The potential to antioxidant responses and chlorophyll content as biomarkers of metal exposure in C. demersum have been demonstrated

    Decision-making of vestibular schwannoma patients

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    CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma

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    Abstract Background Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients. Methods Tissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median </≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate. Results A high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004). Conclusion Only in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC
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