A chromosome-level genome assembly of the jade perch (Scortum barcoo).

Endemic to Australia, jade perch (Scortum barcoo) is a highly profitable freshwater bass species. It has extraordinarily high levels of omega-3 polyunsaturated fatty acids (PUFAs), which detailed genes involved in are largely unclear. Meanwhile, there were four chromosome-level bass species have been previous sequenced, while the bass ancestor genome karyotypes have not been estimated. Therefore, we sequenced, assembled and annotated a genome of jade perch to characterize the detailed genes for biosynthesis of omega-3 PUFAs and to deduce the bass ancestor genome karyotypes. We constructed a chromosome-level genome assembly with 24 pairs of chromosomes, 657.7 Mb in total length, and the contig and the scaffold N50 of 4.8 Mb and 28.6 Mb respectively. We also identified repetitive elements (accounting for 19.7% of the genome assembly) and predicted 26,905 protein-coding genes. Meanwhile, we performed genome-wide localization and characterization of several important genes encoding some key enzymes in the biosynthesis pathway of PUFAs. These genes may contribute to the high concentration of omega-3 in jade perch. Moreover, we conducted a series of comparative genomic analyses among four representative bass species at a chromosome level, resulting in a series of sequences of a deductive bass ancestor genome.

Smad4 Deficiency Promotes Pancreatic Cancer Immunogenicity by Activating the Cancer-Autonomous DNA-Sensing Signaling Axis.

Smad4, a key mediator of the transforming growth factor-ß signaling, is mutated or deleted in 20% of pancreatic ductal adenocarcinoma (PDAC) cancers and significantly affects cancer development. However, the effect of Smad4 loss on the immunogenicity and tumor immune microenvironment of PDAC is still unclear. Here, a surprising function of Smad4 in suppressing mouse PDAC tumor immunogenicity is identified. Although Smad4 deletion in tumor cells enhances proliferation in vitro, the in vivo growth of Smad4-deficient PDAC tumor is significantly inhibited on immunocompetent C57BL/6 (B6) mice, but not on immunodeficient mice or CD8+ cell-depleted B6 mice. Mechanistically, Smad4 deficiency significantly increases tumor cell immunogenicity by promoting spontaneous DNA damage and stimulating STING-mediated type I interferon signaling,which contributes to the activation of type 1 conventional dendritic cells (cDC1) and subsequent CD8+ T cells for tumor control. Furthermore, retarded tumor growth of Smad4-deficient PDAC cells on B6 mice is largely reversed when Sting is codeleted, or when the cells are implanted into interferon-alpha receptor-deficientmice or cDC1-deficientmice. Accordingly, Smad4 deficiency promotes PDAC immunogenicity by inducing tumor-intrinsic DNA damage-elicited type I interferon signaling.

VPsero: Rapid Serotyping of Vibrio parahaemolyticus Using Serogroup-Specific Genes Based on Whole-Genome Sequencing Data.

Vibrio parahaemolyticus has emerged as a significant enteropathogen in human and marine habitats worldwide, notably in regions where aquaculture products constitute a major nutritional source. It is a growing cause of diseases including gastroenteritis, wound infections, and septicemia. Serotyping assays use commercially available antisera to identify V. parahaemolyticus strains, but this approach is limited by high costs, complicated procedures, cross-immunoreactivity, and often subjective interpretation. By leveraging high-throughput sequencing technologies, we developed an in silico method based on comparison of gene clusters for lipopolysaccharide (LPSgc) and capsular polysaccharide (CPSgc) by firstly using the unique-gene strategy. The algorithm, VPsero, which exploits serogroup-specific genes as markers, covers 43 K and all 12 O serogroups in serotyping assays. VPsero is capable of predicting serotypes from assembled draft genomes, outputting LPSgc/CPSgc sequences, and recognizing possible novel serogroups or populations. Our tool displays high specificity and sensitivity in prediction toward V. parahaemolyticus strains, with an average sensitivity in serogroup prediction of 0.910 for O and 0.961 for K serogroups and a corresponding average specificity of 0.990 for O and 0.998 for K serogroups.

Punicalagin Prevents Hepatic Steatosis through Improving Lipid Homeostasis and Inflammation in Liver and Adipose Tissue and Modulating Gut Microbiota in Western Diet-Fed Mice.

SCOPE: Punicalagin (PU)-rich pomegranate peel extract has been shown before to exert protective effects against high fat-induced hepatic damage. The aim of this study is to explore whether and how PU antagonizes hepatic steatosis in Western diet-fed (WD) mice. METHODS AND RESULTS: Mice are fed either chow diet, WD (containing 42% fat, 15% protein, and 43% carbohydrates), or WD supplemented with PU (50 mg kg-1 body weight/day) for 13 weeks. Weight gain, hepatic fat content, and inflammation in the liver and adipose tissues are measured. Compared to the WD group, PU-treated mice have lower fat content, decreased levels of alanine transaminase, and inflammation in liver. PU also changed the transcriptional expression of important genes in fatty acid oxidation pathway and alleviated glucose intolerance. Furthermore, PU improved adiponectin signaling and lipid metabolism in visceral adipose tissue. Moreover, PU improved gut microbiota dysbiosis induced by WD and enhanced gut barrier function. CONCLUSIONS: The findings suggest that PU improves hepatic steatosis induced by WD, in part through regulating lipid homeostasis and inflammation in liver and adipose tissue and restoring microbiota shift and impaired gut barrier function. Thus, PU can be potentially developed as a potential prevention strategy in combating nonalcoholic fatty liver disease.

Characterization of two kcnk3 genes in Nile tilapia (Oreochromis niloticus): Molecular cloning, tissue distribution, and transcriptional changes in various salinity of seawater.

As one important member of the two-pore-domain potassium channel (K2P) family, potassium channel subfamily K member 3 (KCNK3) has been reported for thermogenesis regulation, energy homeostasis, membrane potential conduction, and pulmonary hypertension in mammals. However, its roles in fishes are far less examined and published. In the present study, we identified two kcnk3 genes (kcnk3a and kcnk3b) in an euryhaline fish, Nile tilapia (Oreochromis niloticus), by molecular cloning, genomic survey and laboratory experiments to investigate their potential roles for osmoregulation. We obtained full-length coding sequences of the kcnk3a and kcnk3b genes (1209 and 1173 bp), which encode 402 and 390 amino acids, respectively. Subsequent multiple sequence alignments, putative 3D-structure model prediction, genomic survey and phylogenetic analysis confirmed that two kcnk3 paralogs are widely presented in fish genomes. Interestingly, a DNA fragment inversion of a kcnk3a cluster was found in Cypriniforme in comparison with other fishes. Quantitative real-time PCRs demonstrated that both the tilapia kcnk3 genes were detected in all the examined tissues with a similar distribution pattern, and the highest transcriptions were observed in the heart. Meanwhile, both kcnk3 genes in the gill were proved to have a similar transcriptional change pattern in response to various salinity of seawater, implying that they might be involved in osmoregulation. Furthermore, three predicted transcription factors (arid3a, arid3b, and arid5a) of both kcnk3 genes also showed a similar pattern as their target genes in response to the various salinity, suggesting their potential positive regulatory roles. In summary, we for the first time characterized the two kcnk3 genes in Nile tilapia, and demonstrated their potential involvement in osmoregulation for this economically important fish.

Molecular cloning of two kcnk3 genes from the Northern snakehead (Channa argus) for quantification of their transcriptions in response to fasting and refeeding.

Potassium channel subfamily K member 3 (KCNK3) has been reported to play important roles in membrane potential conduction, pulmonary hypertension and thermogenesis regulation in mammals. However, its roles remain largely unknown and scarce reports were seen in fish. In the present study, we for the first time identified two kcnk3 genes (kcnk3a and kcnk3b) from the carnivorous Northern snakehead (Channa argus) by molecular cloning and a genomic survey. Subsequently, their transcription changes in response to different feeding status were investigated. Full-length coding sequences of the kcnk3a and kcnk3b genes are 1203 and 1176 bp, encoding 400 and 391 amino acids, respectively. Multiple alignments, 3D-structure prediction and phylogenetic analysis further suggested that these kcnk3 genes may be highly conserved in vertebrates. Tissue distribution analysis by real-time PCR demonstrated that both the snakehead kcnk3s were widely transcribed in majority of the examined tissues but with different distribution patterns. In a short-term (24-h) fasting experiment, we observed that brain kcnk3a and kcnk3b genes showed totally opposite transcription patterns. In a long-term (2-week) fasting and refeeding experiment, we also observed differential change patterns for the brain kcnk3 genes. In summary, our findings suggest that the two kcnk3 genes are close while present different transcription responses to fasting and refeeding. They therefore can be potentially selected as novel target genes for improvement of production and quality of this economically important fish.