18 research outputs found
The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer
The availability of bromodomain and extra-terminal inhibitors (BETi) has enabled translational epigenetic studies in cancer. BET proteins regulate transcription by selectively recognizing acetylated lysine residues on chromatin. BETi compete with this process leading to both downregulation and upregulation of gene expression. Hypoxia enables progression of triple negative breast cancer (TNBC), the most aggressive form of breast cancer, partly by driving metabolic adaptation, angiogenesis and metastasis through upregulation of hypoxia-regulated genes (for example, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor A (VEGF-A). Responses to hypoxia can be mediated epigenetically, thus we investigated whether BETi JQ1 could impair the TNBC response induced by hypoxia and exert anti-tumour effects. JQ1 significantly modulated 44% of hypoxia-induced genes, of which two-thirds were downregulated including CA9 and VEGF-A. JQ1 prevented HIF binding to the hypoxia response element in CA9 promoter, but did not alter HIF expression or activity, suggesting some HIF targets are BET-dependent. JQ1 reduced TNBC growth in vitro and in vivo and inhibited xenograft vascularization. These findings identify that BETi dually targets angiogenesis and the hypoxic response, an effective combination at reducing tumour growth in preclinical studies
The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease
Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of
potato shoots and generally results in unusable tubers. This disease has led to
multi-million dollar losses for growers in the central and western United States
over the past decade and impacts the livelihood of potato farmers in Mexico and
New Zealand. ZC is associated with ‘Candidatus
Liberibacter solanacearum’, a fastidious alpha-proteobacterium that is
transmitted by a phloem-feeding psyllid vector, Bactericera
cockerelli Sulc. Research on this disease has been hampered by a
lack of robust culture methods and paucity of genome sequence information for
‘Ca. L. solanacearum’. Here we present the
sequence of the 1.26 Mbp metagenome of ‘Ca. L.
solanacearum’, based on DNA isolated from potato psyllids. The coding
inventory of the ‘Ca. L. solanacearum’ genome was
analyzed and compared to related Rhizobiaceae to better
understand ‘Ca. L. solanacearum’ physiology and
identify potential targets to develop improved treatment strategies. This
analysis revealed a number of unique transporters and pathways, all potentially
contributing to ZC pathogenesis. Some of these factors may have been acquired
through horizontal gene transfer. Taxonomically, ‘Ca. L.
solanacearum’ is related to ‘Ca. L.
asiaticus’, a suspected causative agent of citrus huanglongbing, yet many
genome rearrangements and several gene gains/losses are evident when comparing
these two Liberibacter. species. Relative to ‘Ca. L.
asiaticus’, ‘Ca. L. solanacearum’ probably
has reduced capacity for nucleic acid modification, increased amino acid and
vitamin biosynthesis functionalities, and gained a high-affinity iron transport
system characteristic of several pathogenic microbes
An integrated analysis tool for analyzing hybridization intensities and genotypes using new-generation population-optimized human arrays
Technology Enhanced PBL in HCI Education: A Case Study
Problem Based Learning (PBL) is an instructional method in which
the base for learning is a real-world problem. A typical PBL setting is comprised
of students working together on an authentic problem, using simple tools
such as whiteboards and stationery. Online tools and multimedia technologies
have also been used to support PBL activities. There is however no empirical
work on the blended use of both physical and digital tools. This paper presents a
case study in which we employed PBL pedagogy for the teaching of a postgraduate
course in Human Computer Interaction (HCI). The activities were
situated in a multimodal information space, rich in digital and physical elements
including personal computers, projectors with downwards projection, tablets,
iPods, digital pen readers, stationery and a Facebook group for each team. We
administrated questionnaires assessing students’ motivational beliefs and overall
satisfaction with the learning experience. Our results show that students’
overall satisfaction was highly rated, while the information space contributed to
students’ engagement and collaboration