Background The Southern Ocean is the coldest ocean on Earth but a hot spot of evolution. The bottom-dwelling Eocene ancestor of Antarctic notothenioid fishes survived polar marine glaciation and underwent adaptive radiation, forming >120 species that fill all water column niches today. Genome-wide changes enabling physiological adaptations and the rapid expansion of the Antarctic notothenioids remain poorly understood. Results We sequenced and compared 2 notothenioid genomes—the cold-adapted and neutrally buoyant Antarctic toothfish Dissostichus mawsoni and the basal Patagonian robalo Eleginops maclovinus , representing the temperate ancestor. We detected >200 protein gene families that had expanded and thousands of genes that had evolved faster in the toothfish, with diverse cold-relevant functions including stress response, lipid metabolism, protein homeostasis, and freeze resistance. Besides antifreeze glycoprotein, an eggshell protein had functionally diversified to aid in cellular freezing resistance. Genomic and transcriptomic comparisons revealed proliferation of selcys–transfer RNA genes and broad transcriptional upregulation across anti-oxidative selenoproteins, signifying their prominent role in mitigating oxidative stress in the oxygen-rich Southern Ocean. We found expansion of transposable elements, temporally correlated to Antarctic notothenioid diversification. Additionally, the toothfish exhibited remarkable shifts in genetic programs towards enhanced fat cell differentiation and lipid storage, and promotion of chondrogenesis while inhibiting osteogenesis in bone development, collectively contributing to the achievement of neutral buoyancy and pelagicism. Conclusions Our study revealed a comprehensive landscape of evolutionary changes essential for Antarctic notothenioid cold adaptation and ecological expansion. The 2 genomes are valuable resources for further exploration of mechanisms underlying the spectacular notothenioid radiation in the coldest marine environment.

Transcriptional plasticity is a major driver of phenotypic differences between species. The lower temperature limit (LTL), namely the lower end of survival temperature, is an important trait delimiting the geographical distribution of a species, however, the genetic mechanisms are poorly understood. We investigated the inter-species transcriptional diversification in cold responses between zebrafish Danio rerio and tilapia Oreochromis niloticus, which were reared at a common temperature (28 °C) but have distinct LTLs. We identified significant expressional divergence between the two species in the orthologous genes from gills when the temperature cooled to the LTL of tilapia (8 °C). Five KEGG pathways were found sequentially over-represented in the zebrafish/tilapia divergently expressed genes in the duration (12 hour) of 8 °C exposure, forming a signaling cascade from metabolic regulation to apoptosis via FoxO signaling. Consistently, we found differential progression of apoptosis in the gills of the two species in which zebrafish manifested a delayed and milder apoptotic phenotype than tilapia, corresponding with a lower LTL of zebrafish. We identified diverged expression in 25 apoptosis-related transcription factors between the two species which forms an interacting network with diverged factors involving the FoxO signaling and metabolic regulation. We propose a genetic network which regulates LTL in fishes.

Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.

Background Recent studies showed that circRNAs are involved in the biological process of some human cancers. However, little is known about their functions in colorectal cancer (CRC). Methods Here we first revealed the expression profiles of circRNAs in the CRC tissues and the adjacent non-tumorous tissues using high-throughput sequencing. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs were also explored. The miRNA and mRNA expression profiles were then obtained by analyzing relevant CRC data retrived from the TCGA database. We obtained and analyzed the competing endogenous RNA (ceRNA) network of the top three pairs of the largest up-regulated and down-regulated circRNAs. Results In this study, we obtained 50,410 circRNAs in the CRC tissue and the adjacent non-tumor tissues, of which 33.7% (16,975) were new, and revealed differential changes in circRNA expression during colorectal carcinogenesis. We have identified six potential key circRNAs (circPIEZO1-3, hsa_circ_0067163, hsa_circ_0140188, hsa_circ_0002632, hsa_circ_0001998 and hsa_circ_0023990) associated with CRC, which play important roles in carcinogenesis as ceRNA for regulation of miRNA-mRNA network. In the subsequent KEGG analysis, several CRC-related pathways were found. Conclusions Our findings advance the understanding of the pathogenesis of CRC from the perspective of circRNAs and provide some circRNAs as candidate diagnostic biomarkers or potential therapeutic targets.

Semantic segmentation is a process of linking each pixel in an image to a class label, and is widely used in the field of autonomous vehicles and robotics. Although deep learning methods have already made great progress for semantic segmentation, they either achieve great results with numerous parameters or design lightweight models but heavily sacrifice the segmentation accuracy. Because of the strict requirements of real-world applications, it is critical to design an effective real-time model with both competitive segmentation accuracy and small model capacity. In this paper, we propose a lightweight network named DABNet, which employs Depth-wise Asymmetric Bottleneck (DAB) and Point-wise Aggregation Decoder (PAD) module to tackle the challenging real-time semantic segmentation in urban scenes. Specifically, the DAB module creates a sufficient receptive field and densely utilizes the contextual information, and the PAD module aggregates the feature maps of different scales to optimize performance through the attention mechanism. Compared with existing methods, our network substantially reduces the number of parameters but still achieves high accuracy with real-time inference ability. Extensive ablation experiments on two challenging urban scene datasets (Cityscapes and CamVid) have proved the effectiveness of the proposed approach in real-time semantic segmentation.INDEX TERMS Real-time semantic segmentation, encoder-decoder network, convolutional neural network, urban scenes, lightweight network.