We present a new de novo transcriptome assembler, Bridger, which takes advantage of techniques employed in Cufflinks to overcome limitations of the existing de novo assemblers. When tested on dog, human, and mouse RNA-seq data, Bridger assembled more full-length reference transcripts while reporting considerably fewer candidate transcripts, hence greatly reducing false positive transcripts in comparison with the state-of-the-art assemblers. It runs substantially faster and requires much less memory space than most assemblers. More interestingly, Bridger reaches a comparable level of sensitivity and accuracy with Cufflinks. Bridger is available at https://sourceforge.net/projects/rnaseqassembly/files/?source=navbar.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0596-2) contains supplementary material, which is available to authorized users.

Mutations in the FOXA1 transcription factor define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. By annotating the FOXA1 mutation landscape from 3086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (~50% of all mutations) and R219 (~5%), a highly conserved DNA contact residue. Clinically, Wing2 mutations are seen in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumors with neuroendocrine histology. Interrogation of the biologic properties of FOXA1WT and 14 FOXA1 mutants revealed gain-of-function in mouse prostate organoid proliferation assays. 12 of these mutants, as well as FOXA1WT, promoted an exaggerated pro-luminal differentiation program whereas two different R219 mutants blocked luminal differentiation and activate a mesenchymal and neuroendocrine transcriptional program. ATAC-seq of FOXA1WT and representative Wing2 and R219 mutants revealed dramatic, mutant-specific changes in open chromatin at thousands of genomic loci, together with novel sites of FOXA1 binding and associated increases in gene expression. Of note, peaks in R219 mutant expressing cells lack the canonical core FOXA1 binding motifs (GTAAAC/T) but are enriched for a related, non-canonical motif (GTAAAG/A), which is preferentially activated by R219 mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its normal pioneering function through perturbation of normal luminal epithelial differentiation programs, providing further support to the role of lineage plasticity in cancer progression.

Chitosan has been shown to be a promising scaffold for various applications in tissue engineering. In this study, a chitosan-gelatin complex was fabricated as a scaffold by a freezing and lyophilizing technique. Chitosan's structure and characteristics are similar to those of glycosaminoglycan (GAG) and its analogs, and possesses various biological activities, whereas gelatin can serve as a substrate for cell adhesion, differentiation, and proliferation. With the use of autologous chondrocytes isolated from pig's auricular cartilage and seeded onto the chitosan-gelatin scaffold, elastic cartilages have been successfully engineered at the porcine abdomen subcutaneous tissue. After 16 weeks of implantation, the engineered elastic cartilages have acquired not only normal histological and biochemical, but also mechanical properties. The tissue sections of the engineered elastic cartilages showed that the chondrocytes were enclosed in the lacuna, similar to that of native cartilage. The presence of elastic fibers in the engineered cartilages was also demonstrated by Vehoeff's staining, and immunohistochemical staining confirmed the presence of type II collagen in the engineered cartilages. Quantitatively, the GAG in the engineered cartilages reached 90% of the concentration in native auricular cartilage. Furthermore, biomechanical analysis demonstrated that the extrinsic stiffness of the engineered cartilages reached 85% of the level in native auricular cartilage when it was harvested at 16 weeks. Thus, this study demonstrated that the chitosan-gelatin complex may serve as a suitable scaffold for cartilage tissue engineering.

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Shifts in rainfall and rising temperatures due to climate change poses a formidable challenge to the sustainability of broadacre crop yields in Western and SouthEastern Australia. Output from18 Global Climate Models (GCMs) for the Special Report on Emission Scenarios (SRES) A2 scenario was statistically downscaled to four contrasting locations. For the first time in these regions, bias corrected statistically downscaled climate data were employed to drive the Agricultural Production Systems Simulator (APSIM) crop model that integrates the effects of soil, crop phenotype, and management options for a quantitative comparison of crop yields and phenology under an historical and a plausible projected climate. The dynamic APSIM simulation model explore the implications of climate change across multiple locations and multiple time periods (1961-2010, 2030, 2060 and 2090) for multiple key crops (wheat, barley, lupin, canola, field pea) grown in three different types of soil. On average, the ensemble of downscaled GCM projections show a decrease in rainfall in the future at the four locations considered, with increased variability at two locations. At all locations and for five crops, future changes in both crop biomass and grain yield are strongly associated with changes in rainfall (P = 0.05 to P = 0.001). The overall rainfall amount is critical in determining yields but, equally, higher future temperatures can contribute to reducing crop productivity primarily due to advanced crop phenology. For example, for wheat cropping at Hamilton (a higher rainfall site), there is a significant advancement in median flowering date for 2030, 2060, and 2090 of 10, 18, and 29 days respectively with a significant 0.50% grain yield changes for each percentage change in rainfall compared to significant 0.90% grain yield changes in Cunderdin (a lower rainfall sites). At all sites except Hamilton, the change in crop grain yield is significantly correlated (P=0.001) with the percentage change in the future rainfall and the impact increased progressively from higher rainfall to lower rainfall sites. However, the magnitude of the change in crop phenology and yield were not significantly different between soil types. These results help to define regions of concern and their relative importance in the coming years. In this future climate the negative consequences for crop yields and advancement of phenology relative to baseline are not uniform across crops and locations. Of the crops studied-wheat, barley, lupin, canola and field pea-field pea is the most sensitive to the projected future climate changes, and the ensemble median changes in field pea yield range from a decrease of 12% to a decrease of 45%, depending on location. These results highlight the importance of research and policy to support strategies for adapting to climate change, such as advances in agronomy, soil moisture conservation, seasonal climate forecasting and breeding new crop varieties.