Stromal upregulation of lateral epithelial adhesions : gene expression analysis of signalling pathways in prostate epithelium

BACKGROUND: Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. METHODS: Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model. RESULTS: TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1). CONCLUSIONS: In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.

Gene expression profile of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure

BACKGROUND: Broccoli consumption has been associated with a reduced risk of prostate cancer. Isothiocyanates (ITCs) derived from glucosinolates that accumulate in broccoli are dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) derives from heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) from sprouting broccoli. While there are many studies regarding the biological activity of SF, mainly undertaken with cancerous cells, there are few studies associated with IB. METHODS: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these cells, and to quantify changes in gene expression following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. RESULTS: Global gene expression profiling identified epithelial and stromal-specific gene expression profiles. SF induced more changes in epithelial cells, whereas IB was more effective in stromal cells. Although IB and SF induced different changes in gene expression in both epithelial and stromal cells, these were associated with similar pathways, such as cell cycle and detoxification. Both ITCs increased expression of PLAGL1, a tumor suppressor gene, in stromal cells and suppressed expression of the putative tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. CONCLUSION: These data suggest that IB and SF both alter genes associated with cancer prevention, and IB should be investigated further as a potential chemopreventative agent.

mCOPA: analysis of heterogeneous features in cancer expression data

Background Cancer outlier profile analysis (COPA) has proven to be an effective approach to analyzing cancer expression data, leading to the discovery of the TMPRSS2 and ETS family gene fusion events in prostate cancer. However, the original COPA algorithm did not identify down-regulated outliers, and the currently available R package implementing the method is similarly restricted to the analysis of over-expressed outliers. Here we present a modified outlier detection method, mCOPA, which contains refinements to the outlier-detection algorithm, identifies both over- and under-expressed outliers, is freely available, and can be applied to any expression dataset. Results We compare our method to other feature-selection approaches, and demonstrate that mCOPA frequently selects more-informative features than do differential expression or variance-based feature selection approaches, and is able to recover observed clinical subtypes more consistently. We demonstrate the application of mCOPA to prostate cancer expression data, and explore the use of outliers in clustering, pathway analysis, and the identification of tumour suppressors. We analyse the under-expressed outliers to identify known and novel prostate cancer tumour suppressor genes, validating these against data in Oncomine and the Cancer Gene Index. We also demonstrate how a combination of outlier analysis and pathway analysis can identify molecular mechanisms disrupted in individual tumours. Conclusions We demonstrate that mCOPA offers advantages, compared to differential expression or variance, in selecting outlier features, and that the features so selected are better able to assign samples to clinically annotated subtypes. Further, we show that the biology explored by outlier analysis differs from that uncovered in differential expression or variance analysis. mCOPA is an important new tool for the exploration of cancer datasets and the discovery of new cancer subtypes, and can be combined with pathway and functional analysis approaches to discover mechanisms underpinning heterogeneity in cancers

‘I always look under the bed for a man’. Needs and barriers to the expression of sexuality in residential aged care: the views of residents with and without dementia

Objectives: This qualitative study canvassed residents' perceptions of the needs and barriers to the expression of sexuality in long-term care. Methods: Sixteen residents, including five with dementia, from six aged care facilities in two Australian states were interviewed. Data were analysed using a constant comparative method. Results: Four categories describe residents' views about sexuality, their needs and barriers to its expression: ‘It still matters’; ‘Reminiscence and resignation’, ‘It's personal’, and ‘It's an unconducive environment’. Discussion: Residents, including those with dementia, saw themselves as sexual beings and with a continuing need and desire to express their sexuality. The manner in which it was expressed varied. Many barriers to sexual expression were noted, including negative attitudes of staff, lack of privacy and limited opportunities for the establishment of new relationships or the continuation of old ones. Interviewees agreed that how a resident expressed their sexuality was their business and no one else's.

Characterization of sky-region morphological-temporal airborne collision detection

Automated airborne collision-detection systems are a key enabling technology for facilitat- ing the integration of unmanned aerial vehicles (UAVs) into the national airspace. These safety-critical systems must be sensitive enough to provide timely warnings of genuine air- borne collision threats, but not so sensitive as to cause excessive false-alarms. Hence, an accurate characterisation of detection and false alarm sensitivity is essential for understand- ing performance trade-offs, and system designers can exploit this characterisation to help achieve a desired balance in system performance. In this paper we experimentally evaluate a sky-region, image based, aircraft collision detection system that is based on morphologi- cal and temporal processing techniques. (Note that the examined detection approaches are not suitable for the detection of potential collision threats against a ground clutter back- ground). A novel collection methodology for collecting realistic airborne collision-course target footage in both head-on and tail-chase engagement geometries is described. Under (hazy) blue sky conditions, our proposed system achieved detection ranges greater than 1540m in 3 flight test cases with no false alarm events in 14.14 hours of non-target data (under cloudy conditions, the system achieved detection ranges greater than 1170m in 4 flight test cases with no false alarm events in 6.63 hours of non-target data). Importantly, this paper is the first documented presentation of detection range versus false alarm curves generated from airborne target and non-target image data.

Effect of bone morphogenetic protein-4 (BMP-4) on the expression of Sox2, Oct-4 and c-Myc in human periodontal ligament cells during long-term culture

Recent studies demonstrated endogenous expression level of Sox2, Oct-4 and c-Myc is correlated with the pluripotency and successful induction of induced pluripotent stem cells (iPSCs). Periondontal ligament cells (PDLCs)have multi-lineage diferentiation capability and ability to maintain undifferentiated stage, which makes PDLCs a suitable cell source for tissue repair and regeneration. To elucidate the effect of in vitro culture condition on the stemness potential of PDLCs, we explored the cell growth, proliferation, cell cycle, and the expression of Sox2, Oct-4 and c-Myc in PDLCs from passage 1 to 7 with or without the addition of recombinant human BMP4(rhBMP4). Our results revealed that BMP-4 promoted cell growth and proliferation, arrested PDLCs in S phase of cell cycle and upregulated PI value. It was revealed that without the addition of rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs only maintained nucleus location until passage 3, then lost nucleus location subsequently. The mRNA expression in PDLCs further confirmed that the level of Sox2 and Oct-4 peaked at passage 3, then decreased afterwards, whereas c-Myc maintained consistently upregulation along passages. after the treatment with rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs maintained nucleus location even at passage 7 and the mRNA expression of Sox2 and Oct-4 significantly upregulated at passage 5 and 7. These results demonstrated that addition of rhBMP-4 in the culture media could improve the current culture condition for PDLCs to maintain in an undifferentiated stage.

Spatio temporal feature evaluation for action recognition

Spatio-Temporal interest points are the most popular feature representation in the field of action recognition. A variety of methods have been proposed to detect and describe local patches in video with several techniques reporting state of the art performance for action recognition. However, the reported results are obtained under different experimental settings with different datasets, making it difficult to compare the various approaches. As a result of this, we seek to comprehensively evaluate state of the art spatio- temporal features under a common evaluation framework with popular benchmark datasets (KTH, Weizmann) and more challenging datasets such as Hollywood2. The purpose of this work is to provide guidance for researchers, when selecting features for different applications with different environmental conditions. In this work we evaluate four popular descriptors (HOG, HOF, HOG/HOF, HOG3D) using a popular bag of visual features representation, and Support Vector Machines (SVM)for classification. Moreover, we provide an in-depth analysis of local feature descriptors and optimize the codebook sizes for different datasets with different descriptors. In this paper, we demonstrate that motion based features offer better performance than those that rely solely on spatial information, while features that combine both types of data are more consistent across a variety of conditions, but typically require a larger codebook for optimal performance.