Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer

Simultaneous expression of highly homologous RLN1 and RLN2 genes in prostate impairs their accurate delineation. We used PacBio SMRT sequencing and RNA-Seq in LNCaP cells in order to dissect the expression of RLN1 and RLN2 variants. We identified a novel fusion transcript comprising the RLN1 and RLN2 genes and found evidence of its expression in the normal and prostate cancer tissues. The RLN1-RLN2 fusion putatively encodes RLN2 isoform with the deleted secretory signal peptide. The identification of the fusion transcript provided information to determine unique RLN1-RLN2 fusion and RLN1 regions. The RLN1-RLN2 fusion was co-expressed with RLN1 in LNCaP cells, but the two gene products were inversely regulated by androgens. We showed that RLN1 is underrepresented in common PCa cell lines in comparison to normal and PCa tissue. The current study brings a highly relevant update to the relaxin field, and will encourage further studies of RLN1 and RLN2 in PCa and broader.

Partial intervertebral fusion secures successful outcomes after thoracoscopic anterior scoliosis correction: A low-dose computed tomography study

Study Design Retrospective review of prospectively collected data. Objectives To analyze intervertebral (IV) fusion after thoracoscopic anterior spinal fusion (TASF) and explore the relationship between fusion scores and key clinical variables. Summary of Background Information TASF provides comparable correction with some advantages over posterior approaches but reported mechanical complications, and their relationship to non-union and graft material is unclear. Similarly, the optimal combination of graft type and implant stiffness for effecting successful radiologic union remains undetermined. Methods A subset of patients from a large single-center series who had TASF for progressive scoliosis underwent low-dose computed tomographic scans 2 years after surgery. The IV fusion mass in the disc space was assessed using the 4-point Sucato scale, where 1 indicates <50% and 4 indicates 100% bony fusion of the disc space. The effects of rod diameter, rod material, graft type, fusion level, and mechanical complications on fusion scores were assessed. Results Forty-three patients with right thoracic major curves (mean age 14.9 years) participated in the study. Mean fusion scores for patient subgroups ranged from 1.0 (IV levels with rod fractures) to 2.2 (4.5-mm rod with allograft), with scores tending to decrease with increasing rod size and stiffness. Graft type (autograft vs. allograft) did not affect fusion scores. Fusion scores were highest in the middle levels of the rod construct (mean 2.52), dropping off by 20% to 30% toward the upper and lower extremities of the rod. IV levels where a rod fractured had lower overall mean fusion scores compared to levels without a fracture. Mean total Scoliosis Research Society (SRS) questionnaire scores were 98.9 from a possible total of 120, indicating a good level of patient satisfaction. Conclusions Results suggest that 100% radiologic fusion of the entire disc space is not necessary for successful clinical outcomes following thoracoscopic anterior selective thoracic fusion.

Fusion transcript loci share many genomic features with non-fusion loci

Background Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription. Results We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76 %) of these fusion transcripts were ‘read-through chimeras’ derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76 %) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85 %) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes. Conclusions Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions.

Fusion of worlds?: Consumers' self-narrative in a hybrid digital/physical world

As the Internet becomes deeply embedded in consumers' life and continuously accessed through mobile devices, the boundary between the digital and the physical becomes less defined. This thesis investigates how this blurring boundary impacts on consumers' construction of their self-narrative and found that consumers' narrative is paradoxically coherent and fragmented and depicts a heroic story of the self. Prior studies show consumers achieve their desired life story through meaningful consumption, however, the notion of fragmented lives are challenged. Further, extensive digital leisure consumption is often viewed in a less positive light. Nevertheless, consumers, who significantly consume digital leisure, do not disregard their physical world or favour one space over the other. Rather, they negotiate key aspects from their digital and physical lives and fluidly move between these two worlds, creating a hybrid narrative that saves their self and others.

Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: A cohort study

Aim Scoliosis is a common co-morbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Method Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. Results After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12–0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06–0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16–1.03; p=0.06). Interpretation With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

A data fusion approach of multiple maintenance data sources for real-world reliability modelling

A central tenet in the theory of reliability modelling is the quantification of the probability of asset failure. In general, reliability depends on asset age and the maintenance policy applied. Usually, failure and maintenance times are the primary inputs to reliability models. However, for many organisations, different aspects of these data are often recorded in different databases (e.g. work order notifications, event logs, condition monitoring data, and process control data). These recorded data cannot be interpreted individually, since they typically do not have all the information necessary to ascertain failure and preventive maintenance times. This paper presents a methodology for the extraction of failure and preventive maintenance times using commonly-available, real-world data sources. A text-mining approach is employed to extract keywords indicative of the source of the maintenance event. Using these keywords, a Naïve Bayes classifier is then applied to attribute each machine stoppage to one of two classes: failure or preventive. The accuracy of the algorithm is assessed and the classified failure time data are then presented. The applicability of the methodology is demonstrated on a maintenance data set from an Australian electricity company.

Molecular modeling of Bt Cry1Ac (DI–DII)–ASAL (Allium sativum lectin)–fusion protein and its interaction with aminopeptidase N (APN) receptor of Manduca sexta

Genetic engineering of Bacillus thuringiensis (Bt) Cry proteins has resulted in the synthesis of various novel toxin proteins with enhanced insecticidal activity and specificity towards different insect pests. In this study, a fusion protein consisting of the DI–DII domains of Cry1Ac and garlic lectin (ASAL) has been designed in silico by replacing the DIII domain of Cry1Ac with ASAL. The binding interface between the DI–DII domains of Cry1Ac and lectin has been identified using protein–protein docking studies. Free energy of binding calculations and interaction profiles between the Cry1Ac and lectin domains confirmed the stability of fusion protein. A total of 18 hydrogen bonds was observed in the DI–DII–lectin fusion protein compared to 11 hydrogen bonds in the Cry1Ac (DI–DII–DIII) protein. Molecular mechanics/Poisson–Boltzmann (generalized-Born) surface area [MM/PB (GB) SA] methods were used for predicting free energy of interactions of the fusion proteins. Protein–protein docking studies based on the number of hydrogen bonds, hydrophobic interactions, aromatic–aromatic, aromatic–sulphur, cation–pi interactions and binding energy of Cry1Ac/fusion proteins with the aminopeptidase N (APN) of Manduca sexta rationalised the higher binding affinity of the fusion protein with the APN receptor compared to that of the Cry1Ac–APN complex, as predicted by ZDOCK, Rosetta and ClusPro analysis. The molecular binding interface between the fusion protein and the APN receptor is well packed, analogously to that of the Cry1Ac–APN complex. These findings offer scope for the design and development of customized fusion molecules for improved pest management in crop plants.

Bio-inspired multifunctional metallic foams through the fusion of different biological solutions

Nature is a school for scientists and engineers. Inherent multiscale structures of biological materials exhibit multifunctional integration. In nature, the lotus, the water strider, and the flying bird evolved different and optimized biological solutions to survive. In this contribution, inspired by the optimized solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, and superior repellency towards different corrosive solutions. This approach provides an effective avenue to the development of water strider robots and other aquatic smart devices floating on water. Furthermore, the resultant multifunctional metallic foam can be used to construct an oil/water separation apparatus, exhibiting a high separation efficiency and long-term repeatability. The presented approach should provide a promising solution for the design and construction of other multifunctional metallic foams in a large scale for practical applications in the petro-chemical field. Optimized biological solutions continue to inspire and to provide design idea for the construction of multiscale structures with multifunctional integration. Inspired by the optimized biological solutions from the lotus leaf with superhydrophobic self-cleaning, the water strider leg with durable and robust superhydrophobicity, and the lightweight bird bone with hollow structures, multifunctional metallic foams with multiscale structures are fabricated, demonstrating low adhesive superhydrophobic self-cleaning, striking loading capacity, stable corrosion resistance, and oil/water separation.

Decision fusion for reliable flood mapping using remote sensing images

Flood extent mapping is a basic tool for flood damage assessment, which can be done by digital classification techniques using satellite imageries, including the data recorded by radar and optical sensors. However, converting the data into the information we need is not a straightforward task. One of the great challenges involved in the data interpretation is to separate the permanent water bodies and flooding regions, including both the fully inundated areas and the wet areas where trees and houses are partly covered with water. This paper adopts the decision fusion technique to combine the mapping results from radar data and the NDVI data derived from optical data. An improved capacity in terms of identifying the permanent or semi-permanent water bodies from flood inundated areas has been achieved. Computer software tools Multispec and Matlab were used.

Efficient content-based image retrieval based on multi-feature fusion

The increased availability of image capturing devices has enabled collections of digital images to rapidly expand in both size and diversity. This has created a constantly growing need for efficient and effective image browsing, searching, and retrieval tools. Pseudo-relevance feedback (PRF) has proven to be an effective mechanism for improving retrieval accuracy. An original, simple yet effective rank-based PRF mechanism (RB-PRF) that takes into account the initial rank order of each image to improve retrieval accuracy is proposed. This RB-PRF mechanism innovates by making use of binary image signatures to improve retrieval precision by promoting images similar to highly ranked images and demoting images similar to lower ranked images. Empirical evaluations based on standard benchmarks, namely Wang, Oliva & Torralba, and Corel datasets demonstrate the effectiveness of the proposed RB-PRF mechanism in image retrieval.