Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Background/Aims: The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells. Methods: Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells. Results: The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells. Conclusion: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level

Principal-Oscillation-Pattern Analysis of Gene Expression

Principal-oscillation-pattern (POP) analysis is a multivariate and systematic technique for identifying the dynamic characteristics of a system from time-series data. In this study, we demonstrate the first application of POP analysis to genome-wide time-series gene-expression data. We use POP analysis to infer oscillation patterns in gene expression. Typically, a genomic system matrix cannot be directly estimated because the number of genes is usually much larger than the number of time points in a genomic study. Thus, we first identify the POPs of the eigen-genomic system that consists of the first few significant eigengenes obtained by singular value decomposition. By using the linear relationship between eigengenes and genes, we then infer the POPs of the genes. Both simulation data and real-world data are used in this study to demonstrate the applicability of POP analysis to genomic data. We show that POP analysis not only compares favorably with experiments and existing computational methods, but that it also provides complementary information relative to other approaches

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

The Divergence in Bacterial Components Associated with Bactrocera dorsalis across Developmental Stages

Eco-evolutionary dynamics of microbiotas at the macroscale level are largely driven by ecological variables. The diet and living environment of the oriental fruit fly, Bactrocera dorsalis, diversify during development, providing a natural system to explore convergence, divergence, and repeatability in patterns of microbiota dynamics as a function of the host diet, phylogeny, and environment. Here, we characterized the microbiotas of 47 B. dorsalis individuals from three distinct populations by 16S rRNA amplicon sequencing. A significant deviation was found within the larvae, pupae, and adults of each population. Pupae were characterized by an increased bacterial taxonomic and functional diversity. Principal components analysis showed that the microbiotas of larvae, pupae, and adults clearly separated into three clusters. Acetobacteraceae, Lactobacillaceae, and Enterobacteriaceae were the predominant families in larval and adult samples, and PICRUSt analysis indicated that phosphoglycerate mutases and transketolases were significantly enriched in larvae, while phosphoglycerate mutases, transketolases, and proteases were significantly enriched in adults, which may support the digestive function of the microbiotas in larvae and adults. The abundances of Intrasporangiaceae, Dermabacteraceae (mainly Brachybacterium) and Brevibacteriaceae (mainly Brevibacterium) were significantly higher in pupae, and the antibiotic transport system ATP-binding protein and antibiotic transport system permease protein pathways were significantly enriched there as well, indicating the defensive function of microbiotas in pupae. Overall, differences in the microbiotas of the larvae, pupae, and adults are likely to contribute to differences in nutrient assimilation and living environments

Enhanced tendon–bone healing with acidic fibroblast growth factor delivered in collagen in a rabbit anterior cruciate ligament reconstruction model

Abstract Background The objective of the present study was to investigate the effectiveness of acidic fibroblast growth factor delivered in collagen (aFGF/collagen) for promoting tendon–bone interface healing after anterior cruciate ligament (ACL) reconstruction in rabbits. Methods ACL reconstructions were performed in the right hind limbs of New Zealand rabbits. Each left long digital extensor tendon was harvested as an autograft, and collagen incorporating different concentrations of aFGF or same amount of collagen alone was applied at the tendon–bone interface after ACL reconstruction. The control group underwent ACL reconstruction only. There were high and low aFGF/collagen groups, collagen alone group, and control group (n = 21 rabbits per group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks postoperatively to evaluate the effect of aFGF/collagen on tendon–bone interface healing. Results Results of biomechanical tests showed that at both 8 and 12 weeks postoperatively, the elastic modulus and stiffness in both the high and low aFGF/collagen treatment groups were significantly higher than those in the control group and collagen alone group, with that in the high aFGF/collagen concentration group being the highest. Histological analysis showed that at 8 weeks, tightly organized Sharpey-like fibers were observed in both aFGF/collagen groups with new bone growth into the tendon in the high concentration group. At 12 weeks postoperatively, a fibrocartilage transition zone was observed in the bone tunnels in both aFGF/collagen groups, especially in the high aFGF/collagen group. Conclusion Application of the aFGF/collagen composite could enhance early healing at the tendon–bone interface after ACL reconstruction, especially with the use of a high aFGF/collagen concentration

Symbiotic microbiota may reflect host adaptation by resident to invasive ant species

Exotic invasive species can influence the behavior and ecology of native and resident species, but these changes are often overlooked. Here we hypothesize that the ghost ant, Tapinoma melanocephalum, living in areas that have been invaded by the red imported fire ant, Solenopsis invicta, displays behavioral differences to interspecific competition that are reflected in both its trophic position and symbiotic microbiota. We demonstrate that T. melanocephalum workers from S. invicta invaded areas are less aggressive towards workers of S. invicta than those inhabiting non-invaded areas. Nitrogen isotope analyses reveal that colonies of T. melanocephalum have protein-rich diets in S. invicta invaded areas compared with the carbohydrate-rich diets of colonies living in non-invaded areas. Analysis of microbiota isolated from gut tissue shows that T. melanocephalum workers from S. invicta invaded areas also have different bacterial communities, including a higher abundance of Wolbachia that may play a role in vitamin B provisioning. In contrast, the microbiota of workers of T. melanocephalum from S. invicta-free areas are dominated by bacteria from the orders Bacillales, Lactobacillales and Enterobacteriales that may be involved in sugar metabolism. We further demonstrate experimentally that the composition and structure of the bacterial symbiont communities as well as the prevalence of vitamin B in T. melanocephalum workers from S. invicta invaded and non-invaded areas can be altered if T. melanocephalum workers are supplied with either protein-rich or carbohydrate-rich food. Our results support the hypothesis that bacterial symbiont communities can help hosts by buffering behavioral changes caused by interspecies competition as a consequence of biological invasions

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder.

Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p = 2.1E-7), a transcription factor mainly expressed in developmental brain. Gene targets regulated by POU3F2 showed a 2.7-fold enrichment for known ASD genes (p = 2.0E-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p = 7.1E-5). These results provide a novel connection between rare and common variants, whereby ASD genes affected by very rare mutations are regulated by an unlinked transcription factor affected by common genetic variations