A nonalcoholic fatty liver disease cirrhosis model in gerbil:the dynamic relationship between hepatic lipid metabolism and cirrhosis

Nonalcoholic fatty liver disease (NAFLD) usually takes decades to develop into cirrhosis, which limits the longitudinal study of NAFLD. This work aims at developing a NAFLD-caused cirrhosis model in gerbil and examining the dynamic relationship between hepatic lipid metabolism and cirrhosis. We fed gerbil a high-fat and high-cholesterol diet (HFHCD) for 24 weeks, and recorded the gerbil's phenotype at 3, 6, 9, 12, 15, 18, 21, 24 weeks. The model's pathological process, lipid metabolism, oxidative stress, liver collagen deposition and presence of relevant cytokines were tested and evaluated during the full-time frame of disease onset. The gerbil model can induce nonalcoholic steatohepatitis (NASH) within 9 weeks, and can develop cirrhosis after 21 weeks induction. The model's lipids metabolism disorder is accompanied with the liver damage development. During the NAFLD progression, triglycerides (TG) and free fatty acids (FFA) have presented distinct rise and fall tendency, and the turning points are at the fibrosis stage. Besides that, the ratios of total cholesterol (CHO) to high-density lipoprotein cholesterol (HDL-C) exhibited constant growth tendency, and have a good linear relationship with hepatic stellate cells (HSC) (R-2 = 0.802, P <0.001). The gerbil NAFLD cirrhosis model has been developed and possesses positive correlation between lipids metabolism and cirrhosis. The compelling rise and fall tendency of TG and FFA indicated that the fibrosis progression can lead to impairment in lipoprotein synthesis and engender decreased TG level. CHO/HDL-C ratios can imply the fibrosis progress and be used as a blood indicator for disease prediction and prevention

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000

Genome-wide identification and expression analysis of the PHD-finger gene family in Solanum tuberosum.

Plant homeodomain (PHD) proteins are prevalent in eukaryotes and play important roles in plant growth, development and abiotic stress response. In this study, the comprehensive study of the PHD family (StPHD) was performed in potato (Solanum tuberosum L.). Seventy-two PHD genes (named StPHD1-72) were identified and grouped into 10 subfamilies based on phylogenetic analysis. Similar structure organizations were found within each subfamily according to the exon/intron structures and protein motif analysis. These genes were unequally scattered on the chromosomes of potato, with 9 pairs of segmental duplicated genes and 6 pairs of tandem duplicated genes showing that both segmental duplicated and tandem duplicated events contributed to the expansion of the potato PHD family. The gene ontology (GO) analysis suggests that StPHD mainly functioned at the intracellular level and was involved in various binding, metabolic and regulation processes. The analysis of expression patterns of StPHD genes showed that these genes were differentially expressed in 10 different tissues and responded specifically to heat, salt and drought stress based on the FPKM (Fragments per kilobase of transcript per million mapped reads) values of the RNA-seq data. Furthermore, the real-time quantitative PCR for 12 selected StPHD genes revealed the various levels of gene expression corresponding to abiotic stress. Our results provide useful information for a better understanding of PHD genes and provide the foundation for additional functional exploration of the potato PHD gene family

Selection footprints reflect genomic changes associated with breeding efforts in 56 cucumber inbred lines

Cucumber selective breeding over recent decades has dramatically increased productivity and quality, but the genomic characterizations and changes associated with this breeding history remain unclear. Here, we analyzed the genome resequencing data of 56 artificially selected cucumber inbred lines that exhibit various phenotypes to detect trait-associated sequence variations that reflect breeding improvement. We found that the 56 cucumber lines could be assigned to group 1 and group 2, and the two groups formed a distinctive genetic structure due to the breeding history involving hybridization and selection. Differentially selected regions were identified between group 1 and group 2, with implications for genomic-selection breeding signatures. These regions included known quantitative trait loci or genes that were reported to be associated with agronomic traits. Our results advance knowledge of cucumber genomics, and the 56 selected inbred lines could be good germplasm resources for breeding

Selection footprints reflect genomic changes associated with breeding efforts in 56 cucumber inbred lines

Cucumber selective breeding over recent decades has dramatically increased productivity and quality, but the genomic characterizations and changes associated with this breeding history remain unclear. Here, we analyzed the genome resequencing data of 56 artificially selected cucumber inbred lines that exhibit various phenotypes to detect trait-associated sequence variations that reflect breeding improvement. We found that the 56 cucumber lines could be assigned to group 1 and group 2, and the two groups formed a distinctive genetic structure due to the breeding history involving hybridization and selection. Differentially selected regions were identified between group 1 and group 2, with implications for genomic-selection breeding signatures. These regions included known quantitative trait loci or genes that were reported to be associated with agronomic traits. Our results advance knowledge of cucumber genomics, and the 56 selected inbred lines could be good germplasm resources for breeding.This study was supported by the National Key Research and Development Program of China (2018YFD1000800), the National Natural Science Foundation of China (31830080), the Beijing Municipal Natural Science Foundation (6184043), and the Project of Beijing Agricultural Innovation Consortium (BAIC01)

Toward the positional cloning of qBlsr5a, a QTL underlying resistance to bacterial leaf streak, using overlapping sub-CSSLs in rice.

Bacterial leaf steak (BLS) is one of the most destructive diseases in rice. Studies have shown that BLS resistance in rice is quantitatively inherited, controlled by multiple quantitative trait loci (QTLs). A QTL with relatively large effect, qBlsr5a, was previously mapped in a region of ∼ 380 kb on chromosome 5. To fine map qBlsr5a further, a set of overlapping sub-chromosome segment substitution lines (sub-CSSLs) were developed from a large secondary F2 population (containing more than 7000 plants), in which only the chromosomal region harboring qBlsr5a was segregated. By genotyping the sub-CSSLs with molecular markers covering the target region and phenotyping the sub-CSSLs with artificial inoculation, qBlsr5a was delimited to a 30.0-kb interval, in which only three genes were predicted. qRT-PCR analysis indicated that the three putative genes did not show significant response to the infection of BLS pathogen in both resistant and susceptible parental lines. However, two nucleotide substitutions were found in the coding sequence of gene LOC_Os05g01710, which encodes the gamma chain of transcription initiation factor IIA (TFIIAγ). The nucleotide substitutions resulted in a change of the 39th amino acid from valine (in the susceptible parent) to glutamic acid (in the resistant parent). Interestingly, the resistant parent allele of LOC_Os05g01710 is identical to xa5, a major gene resistant to bacterial leaf blight (another bacterial disease of rice). These results suggest that LOC_Os05g01710 is very possibly the candidate gene of qBlsr5a