The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression.

BACKGROUND: We hypothesised that differences in microRNA expression profiles contribute to the contrasting natural history and clinical outcome of the two most common types of malignant germ cell tumour (GCT), yolk sac tumours (YSTs) and germinomas. RESULTS: By direct comparison, using microarray data for paediatric GCT samples and published qRT-PCR data for adult samples, we identified microRNAs significantly up-regulated in YSTs (n = 29 paediatric, 26 adult, 11 overlapping) or germinomas (n = 37 paediatric). By Taqman qRT-PCR we confirmed differential expression of 15 of 16 selected microRNAs and further validated six of these (miR-302b, miR-375, miR-200b, miR-200c, miR-122, miR-205) in an independent sample set. Interestingly, the miR-302 cluster, which is over-expressed in all malignant GCTs, showed further over-expression in YSTs versus germinomas, representing six of the top eight microRNAs over-expressed in paediatric YSTs and seven of the top 11 in adult YSTs. To explain this observation, we used mRNA expression profiles of paediatric and adult malignant GCTs to identify 10 transcription factors (TFs) consistently over-expressed in YSTs versus germinomas, followed by linear regression to confirm associations between TF and miR-302 cluster expression levels. Using the sequence motif analysis environment iMotifs, we identified predicted binding sites for four of the 10 TFs (GATA6, GATA3, TCF7L2 and MAF) in the miR-302 cluster promoter region. Finally, we showed that miR-302 family over-expression in YST is likely to be functionally significant, as mRNAs down-regulated in YSTs were enriched for 3' untranslated region sequences complementary to the common seed of miR-302a~miR-302d. Such mRNAs included mediators of key cancer-associated processes, including tumour suppressor genes, apoptosis regulators and TFs. CONCLUSIONS: Differential microRNA expression is likely to contribute to the relatively aggressive behaviour of YSTs and may enable future improvements in clinical diagnosis and/or treatment.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Indirect Imaging using Heterodyne Remote Digital Holography

Conventional line-of-sight imaging techniques rely on detecting light paths bouncing from the object and reaching directly to the detector. Absence of any such direct light paths from object to detector results in a failure to recover any useful information using conventional techniques. The absence of direct light paths from object to detector can be observed in several real-world scenarios such as looking around a corner, imaging through turbid media, imaging through tissue etc. The focus of this thesis is pertaining to the problem of looking around corners (or) imaging object hidden from line of sight at macroscopic scales. This thesis focuses on adapting heterodyne interferometry to circumvent the radiometry losses due to scattering and thereby enabling its use in more challenging practical scenarios. Objects hidden around a corner were reconstructed with 500 µm resolution at 0.8 meters standoff. Using heterodyne interferometry and lock-in detection techniques, the hologram of the hidden object could be obtained even under significant radiometry losses without any power matching. Also discussed is the estimation of rapidly varying and slowly varying motion of objects around a corner using doppler shifts and speckle correlations respectively

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Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro‐angiogenic phenotype and increased cell motility and invasiveness

Oncostatin M receptor (OSMR) shows frequent copy number gain and overexpression in advanced cervical squamous cell carcinoma (SCC). We used cell-based in vitro assays, RNA interference, and integrative gene expression profiling to investigate the functional significance of this observation. CaSki and SW756 were selected as representative cervical SCC cells that overexpressed OSMR, and ME180 and MS751 as cells that did not. The STAT-dependent pro-angiogenic factors VEGF-A and ID1 were rapidly induced by OSM in CaSki/SW756 but not in ME180/MS751. However, rapid induction did occur in MS751 following forced OSMR overexpression, while depleting OSMR in CaSki abrogated VEGF-A expression. Conditioned medium from both CaSki and SW756 stimulated endothelial tube formation in vitro, effects that were inhibited by depleting OSMR in the SCC cells. For both CaSki and SW756, migration in a wound healing assay and invasion through Matrigel were stimulated by OSM and consistently inhibited by OSMR depletion. The phenotype was rescued by transfection with OSMR containing a silent mutation that provided specific siRNA resistance. Overall, there was a positive correlation between OSMR levels and invasiveness. We used gene expression profiling to identify genes induced by OSM in CaSki/SW756 but not in ME180/MS751. The most prominent gene ontology category groups for the differentially expressed genes were cell motility/invasion, angiogenesis, signal transduction, and apoptosis. We also profiled 23 cervical SCC samples, identifying genes that were differentially expressed in cases with OSMR overexpression versus those without. Integration of the datasets identified 15 genes that showed consistent differential expression in association with OSMR levels in vitro and in vivo. We conclude that OSMR overexpression in cervical SCC cells provides increased sensitivity to OSM, which induces pro-malignant changes. OSMR is a potential prognostic and therapeutic target in cervical SCC. The genes that mediate OSM:OSMR effects will be valuable indicators of the effectiveness of antibody blockade in pre-clinical systems. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Optimization of process variables for the synthesis of silver nanoparticles by Pycnoporus sanguineus using statistical experimental design

Sequential optimization strategy based on statistical experimental design and one-factor-at-a-time (OFAT) method were employed to optimize the process parameters for the enhancement of silver nanoparticles (AgNPs) production through biological synthesis using Pycnoporus sanguineus. Based on the OFAT method, three significant components influencing the size of AgNPs produced were identified as AgNO3 concentration, incubation temperature, and agitation speed. The optimum values of these process parameter for the synthesis of AgNPs were determined using response surface methodology (RSM) based on Box-Behnken design. The validity of the model developed was verified, and the statistical analysis showed that the optimum operating conditions were 0.001 M of AgNO3, 38°C, and 200 rpm with the smallest AgNPs produced at 14.86 nm. The disc diffusion method also suggested that AgNPs produced using optimum conditions have higher antimicrobial activity compared to the unoptimized AgNPs. The present study developed a robust operating condition for the production of AgNPs by P. sanguineus, which was 8.6-fold smaller than that obtained from un-optimized conditions