Ocean Colour Remote Sensing of Flood Plumes in the Great Barrier Reef

The objective of the research reported in this thesis was to develop a technique to monitor the dynamics of sediments and nutrients entering the coastal ocean with river plumes associated with high intensity low frequency events (e.g. floods), using ocean colour remote sensing. To achieve this objective, an inverse bio-optical model was developed, based on analytical and empirical relationships between concentrations of optically significant substances and remote sensing of water-leaving radiance. The model determines concentrations of water-colouring substances such as chlorophyll, suspended sediments, and coloured dissolved organic matter, as well as the values of optical parameters using water-leaving radiances derived from the Sea-viewing Wide Field-of-view Sensor (SeaWiFS). To solve atmospheric correction in coastal waters, the aerosol type over clear waters is transferred to adjacent turbid water pixels. The vicinity of the Herbert River, central Great Barrier Reef zone, Australia, was used as a case study for the application of the algorithm developed. The satellite ocean colour technique was successfully validated using sea-truth measurements of water-colouring constituents acquired in the area during various seasons throughout 2002-2004. A high correlation between chlorophyll and dissolved organic matter was found in the coastal waters of the region, and when the bio-optical model was constrained to make chlorophyll a function of dissolved organic matter, the relationship between in situ and satellite-derived data was substantially improved. With reliable retrieval of the major water-colouring constituents, the technique was subsequently applied to study fluxes of particulate and dissolved organic and inorganic matter following a flood event in the Herbert River during the austral summer of 1999. Extensive field observations covering a seasonal flood in the Herbert River in February 2004 revealed high sediment and nutrient exports from the river to the adjacent coastal waters during the flood event. Due to rapid settling, the bulk of the sediment-rich influx was deposited close inshore, while the majority of nutrients exported from the river were consumed by phytoplankton in a relatively small area of the coastal ocean. With the help of ocean colour remote sensing, it was demonstrated that river-borne sediments and nutrients discharged by a typical flood in the Herbert River are mostly precipitated or consumed within the first 20 km from the coast and therefore are unlikely to reach and possibly affect the midshelf coral reefs of this section of the Great Barrier Reef lagoon

Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding

The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML

Study of FoxA Pioneer Factor at Silent Genes Reveals Rfx-Repressed Enhancer at Cdx2 and a Potential Indicator of Esophageal Adenocarcinoma Development

Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult mouse liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within conserved sequences, suggesting possible function. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors. We found one such target site at a cryptic “shadow” enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA. The Cdx2 shadow enhancer exhibits a subset of regulatory properties of the upstream Cdx2 promoter region. While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma. By contrast, we find that Rfx1 expression in the esophageal epithelium becomes gradually extinguished during progression to cancer, i.e, expression of Rfx1 decreased markedly in dysplasia and adenocarcinoma. We propose that this decreased expression of Rfx1 could be an indicator of progression from Barrett's esophagus to adenocarcinoma and that similar analyses of other transcription factors bound to silent genes can reveal unanticipated regulatory insights into oncogenic progression and cellular reprogramming

Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding

The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML

[Breweries and malting plants.]

This document on breweries and malting plants has been published within the SPIN project. In this project information has been collected on industrial plants or industrial processes to afford support to governmental policy on emission reduction. This document contains information on the processes, emission sources, emissions to air and water, waste, emission factors, use of energy and energy factors, emission reduction, energy conservation, research on clean technology and standards and licences