Genomic signatures and evolutionary history of the endangered blue-crowned laughingthrush and other Garrulax species.

BACKGROUND: The blue-crowned laughingthrush (Garrulax courtoisi) is a critically endangered songbird endemic to Wuyuan, China, with population of ~323 individuals. It has attracted widespread attention, but the lack of a published genome has limited research and species protection. RESULTS: We report two laughingthrush genome assemblies and reveal the taxonomic status of laughingthrush species among 25 common avian species according to the comparative genomic analysis. The blue-crowned laughingthrush, black-throated laughingthrush, masked laughingthrush, white-browed laughingthrush, and rusty laughingthrush showed a close genetic relationship, and they diverged from a common ancestor between ~2.81 and 12.31 million years ago estimated by the population structure and divergence analysis using 66 whole-genome sequencing birds from eight laughingthrush species and one out group (Cyanopica cyanus). Population inference revealed that the laughingthrush species experienced a rapid population decline during the last ice age and a serious bottleneck caused by a cold wave during the Chinese Song Dynasty (960-1279 AD). The blue-crowned laughingthrush is still in a bottleneck, which may be the result of a cold wave together with human exploitation. Interestingly, the existing blue-crowned laughingthrush exhibits extremely rich genetic diversity compared to other laughingthrushes. These genetic characteristics and demographic inference patterns suggest a genetic heritage of population abundance in the blue-crowned laughingthrush. The results also suggest that fewer deleterious mutations in the blue-crowned laughingthrush genomes have allowed them to thrive even with a small population size. We believe that cooperative breeding behavior and a long reproduction period may enable the blue-crowned laughingthrush to maintain genetic diversity and avoid inbreeding depression. We identified 43 short tandem repeats that can be used as markers to identify the sex of the blue-crowned laughingthrush and aid in its genetic conservation. CONCLUSIONS: This study supplies the missing reference genome of laughingthrush, provides insight into the genetic variability, evolutionary potential, and molecular ecology of laughingthrush and provides a genomic resource for future research and conservation.

Computer-aided assessment of the chemokine receptors CXCR3, CXCR4 and CXCR7 expression in gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a vicious and invasive disease. The major challenge in the clinical treatment of GBC is the lack of a suitable prognosis method. Chemokine receptors such as CXCR3, CXCR4 and CXCR7 play vital roles in the process of tumour progression and metastasis. Their expression levels and distribution are proven to be indicative of the progression of GBC, but are hard to be decoded by conventional pathological methods, and therefore, not commonly used in the prognosis of GBC. In this study, we developed a computer-aided image analysis method, which we used to quantitatively measure the expression levels of CXCR3, CXCR4 and CXCR7 in the nuclei and cytoplasm of glandular and interstitial cells from a cohort of 55 GBC patients. We found that CXCR3, CXCR4 and CXCR7 expressions are associated with the clinicopathological variables of GBC. Cytoplasmic CXCR3, nuclear CXCR7 and cytoplasmic CXCR7 were significant predictive factors of histology invasion, whereas cytoplasmic CXCR4 and nuclear CXCR4 were significantly correlated with T and N stage and were associated with the overall survival and disease-free survival. These results suggest that the quantification and localisation of CXCR3, CXCR4 and CXCR7 expressions in different cell types should be considered using computer-aided assessment to improve the accuracy of prognosis in GBC.

Microbial diversity and community composition of fecal microbiota in dual-purpose and egg type ducks.

Introduction: Ducks are important agricultural animals, which can be divided into egg and dual-purpose type ducks according to economic use. The gut microbiota of ducks plays an important role in their metabolism, immune regulation, and health maintenance. Methods: Here, we use 16S rDNA V4 hypervariable amplicon sequencing to investigate the compositions and community structures of fecal microbiota between egg (five breeds, 96 individuals) and dual-purpose type ducks (four breeds, 73 individuals) that were reared under the same conditions. Results: The alpha diversity of fecal microflora in egg type ducks was significantly higher than that in dual-type ducks. In contrast, there is no significant difference in the fecal microbial community richness between the two groups. MetaStat analysis showed that the abundance of Peptostreptococcaceae, Streptococcaceae, Lactobacillus, Romboutsia, and Campylobacter were significantly different between the two groups. The biomarkers associated with the egg and dual-purpose type ducks were identified using LEfSe analysis and IndVal index. Function prediction of the gut microbiota indicated significant differences between the two groups. The functions of environmental information processing, carbohydrate metabolism, lipid metabolism, xenobiotic biodegradation and metabolism, and metabolism of terpenoids and polyketides were more abundant in egg type ducks. Conversely, the genetic information processing, nucleotide metabolism, biosynthesis of amino acids and secondary metabolites, glycan biosynthesis and metabolism, fatty acid elongation, and insulin resistance were significantly enriched in dual-purpose type ducks. Discussion: This study explored the structure and diversity of the gut microbiota of ducks from different economic-use groups, and provides a reference for improving duck performance by using related probiotics in production.

Identification of Key Candidate Genes for Beak Length Phenotype by Whole-Genome Resequencing in Geese.

The domestic goose is an important economic animal in agriculture and its beak, a trait with high heritability, plays an important role in promoting food intake and defending against attacks. In this study, we sequenced 772 420-day-old Xingguo gray geese (XGG) using a low-depth (~1 ×) whole-genome resequencing strategy. We detected 12,490,912 single nucleotide polymorphisms (SNPs) using the standard GATK and imputed with STITCH. We then performed a genome-wide association study on the beak length trait in XGG. The results indicated that 57 SNPs reached genome-wide significance levels for the beak length trait and were assigned to seven genes, including TAPT1, DHX15, CCDC149, LGI2, SEPSECS, ANAPC4, and Slc34a2. The different genotypes of the most significant SNP (top SNP), which was located upstream of LGI2 and explained 7.24% of the phenotypic variation in beak length, showed significant differences in beak length. Priority-based significance analysis concluded that CCDC149, LGI2, and SEPSECS genes in the most significant quantitative trait locus interval were the most plausible positional and functional candidate genes for beak length development in the XGG population. These findings not only enhance our understanding of the genetic mechanism of the beak length phenotype in geese, but also lay the foundation for further studies to facilitate the genetic selection of traits in geese.

Chromosome-level genome and population genomics reveal evolutionary characteristics and conservation status of Chinese indigenous geese.

Geese are herbivorous birds that play an essential role in the agricultural economy. We construct the chromosome-level genome of a Chinese indigenous goose (the Xingguo gray goose, XGG; Anser cygnoides) and analyze the adaptation of fat storage capacity in the goose liver during the evolution of Anatidae. Genomic resequencing of 994 geese is used to investigate the genetic relationships of geese, which supports the dual origin of geese (Anser cygnoides and Anser anser). Chinese indigenous geese show higher genetic diversity than European geese, and a scientific conservation program can be established to preserve genetic variation for each breed. We also find that a 14-bp insertion in endothelin receptor B subtype 2 (EDNRB2) that determines the white plumage of Chinese domestic geese is a natural mutation, and the linkaged alleles rapidly increase in frequency as a result of genetic hitchhiking, leading to the formation of completely different haplotypes of white geese under strong artificial selection. These genomic resources and our findings will facilitate marker-assisted breeding of geese and provide a foundation for further research on geese genetics and evolution.

A high-quality assembly reveals genomic characteristics, phylogenetic status, and causal genes for leucism plumage of Indian peafowl.

BACKGROUND: The dazzling phenotypic characteristics of male Indian peafowl (Pavo cristatus) are attractive both to the female of the species and to humans. However, little is known about the evolution of the phenotype and phylogeny of these birds at the whole-genome level. So far, there are no reports regarding the genetic mechanism of the formation of leucism plumage in this variant of Indian peafowl. RESULTS: A draft genome of Indian peafowl was assembled, with a genome size of 1.05 Gb (the sequencing depth is 362×), and contig and scaffold N50 were up to 6.2 and 11.4 Mb, respectively. Compared with other birds, Indian peafowl showed changes in terms of metabolism, immunity, and skeletal and feather development, which provided a novel insight into the phenotypic evolution of peafowl, such as the large body size and feather morphologies. Moreover, we determined that the phylogeny of Indian peafowl was more closely linked to turkey than chicken. Specifically, we first identified that PMEL was a potential causal gene leading to the formation of the leucism plumage variant in Indian peafowl. CONCLUSIONS: This study provides an Indian peafowl genome of high quality, as well as a novel understanding of phenotypic evolution and phylogeny of Indian peafowl. These results provide a valuable reference for the study of avian genome evolution. Furthermore, the discovery of the genetic mechanism for the development of leucism plumage is both a breakthrough in the exploration of peafowl plumage and also offers clues and directions for further investigations of the avian plumage coloration and artificial breeding in peafowl.

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer.

PURPOSE: Prostate cancer is the second leading cause of cancer death in men worldwide. Olaparib is clinically approved for the treatment prostate cancer, but cytotoxicity and off-target effects including DNA damage limit its clinical applications. In the current study, new strategies to improve the therapeutic efficacy of olaparib for the treatment of prostate cancer were investigated. METHODS: Two prostate cancer cell lines were exposed to the c-MET inhibitor PHA665752 and/or the PARP inhibitor olaparib. Cell counting kit-8, colony formation assays, and transwell assays were conducted to evaluate the cytotoxicity of olaparib alone or in combination with PHA665752 in prostate cancer cell lines. Western blotting, immunofluorescence staining, and the comet assay were used to assess the effects of PHA665752 on olaparib-induced DNA damage. RESULTS: Combined inhibition of c-MET and PARP resulted in effective and synergistic blocking of the growth of prostate cancer cell lines. Invasion and migration were significantly suppressed when the agents were combined. Mechanistically, dual blocking of PARP and c-MET in prostate cancer cell lines was associated with an impaired DNA damage response. Interestingly, immunofluorescence staining analysis of RAD51 protein indicated that the c-MET inhibitor PHA665752 significantly impaired homologous repair via downregulated translocation of RAD51 into the nucleus in prostate cancer cells. CONCLUSION: The combination of the c-MET inhibitor PHA665752 and the PARP inhibitor olaparib may be a promising therapeutic strategy in patients with prostate cancer.

Primary follicular non-Hodgkin's lymphoma of the ureter: A case report and literature review.

Ureteral cancer is a rare type of neoplasm, with the most prevalent forms including squamous cell carcinoma, transitional cell carcinoma and adenocarcinoma. Ureteral lymphoma is particularly uncommon, and forming a pre-operative diagnosis of the disease is often difficult. The current study describes the case of a 31-year-old man presenting with a space-occupying lesion located in the left lower ureter. Follicular non-Hodgkin's lymphoma was diagnosed via intraoperative frozen section and post-operative pathological analysis. The affected ureteric segment was excised, and the ureter was repaired by end-to-end anastomosis with insertion of a double-J tube for internal drainage. The patient was followed up for 10 months and presented with no signs of recurrence. The current study affirms the importance of pathological examination in the differential diagnosis of ureteral neoplasms and the selection of an appropriate treatment.