摘要: Odorant-binding proteins (OBPs) are crucial in insect's olfactory perception, which participate in the initial step of odorant molecules transporting from the external environment to olfactory receptor neurons. To better understand the roles for OBPs in olfactory perception inCotesia vestalis, a solitary larval endoparasitoid of diamondback moth,Plutella xylostella, we have comprehensively screened the genome ofC. vestalis, and obtained 20 CvesOBPs, including 18 classic OBPs and two minus-C OBPs. Motif-pattern analysis indicates that the motifs ofC. vestalisOBPs are highly conserved in Hymenoptera. The results of tissue expression analysis show that five OBPs (CvesOBP1/11/12/14/16) are highly expressed in male antennae, whereas six other OBP genes (CvesOBP7/8/13/17/18/19) are significantly transcriptionally enriched in female antennae. The results of RNA interference experiments for three most highly expressed OBP genes (CvesOBP17/18/19) in female antennae demonstrate that they are likely involved in parasitic processes of female wasps, as the wasps take a longer time to target the hosts when they are knocked down.

摘要: Iron is essential to life, but surprisingly little is known about how iron is managed in nonvertebrate animals. In mammals, the well-characterizedtransferrinsbind iron and are involved in iron transport or immunity, whereas other members of thetransferrinfamily do not have a role in iron homeostasis. In insects, the functions oftransferrinsare still poorly understood. The goals of this project were to identify thetransferringenes in a diverse set of insect species, resolve the evolutionary relationships among these genes, and predict which of thetransferrinsare likely to have a role in iron homeostasis. Our phylogenetic analysis oftransferrinsfrom 16 orders of insects and two orders of noninsect hexapods demonstrated that there are four orthologous groups of insecttransferrins. Our analysis suggests thattransferrin 2arose prior to the origin of insects, andtransferrins 1,3, and4arose early in insect evolution. Primary sequence analysis of each of the insecttransferrinswas used to predict signal peptides, carboxyl-terminal transmembrane regions, GPI-anchors, and iron binding. Based on this analysis, we suggest thattransferrins 2,3, and4are unlikely to play a major role in iron homeostasis. In contrast, thetransferrin 1orthologs are predicted to be secreted, soluble, iron-binding proteins. We conclude thattransferrin 1orthologs are the most likely to play an important role in iron homeostasis. Interestingly, it appears that the louse, aphid, and thrips lineages have lost thetransferrin 1gene and, thus, have evolved to manage iron withouttransferrins.

摘要: Objectives Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA). Materials and Methods The relative expression of circSLC7A2 was significantly lower in OA tissues than it was in matched controls, as shown by real-time quantitative polymerase chain reaction (RT-qPCR). Western blotting, RT-qPCR and immunofluorescence experiments were employed to evaluate the roles of circSLC7A2, miR-4498 and TIMP3. The in vivo role and mechanism of circSLC7A2 were also conformed in a mouse model. Results circSLC7A2 was decreased in OA model and the circularization of circSLC7A2 was regulated by FUS. Loss of circSLC7A2 reduced the sponge of miR-4498 and further inhibited the expression of TIMP3, subsequently leading to an inflammatory response. We further determined that miR-4498 inhibitor reversed circSLC7A2-knockdown-induced OA phenotypes. Intra-articular injection of circSLC7A2 alleviated in vivo OA progression in a mouse model of anterior cruciate ligament transection (ACLT). Conclusions The circSLC7A2/miR-4498/TIMP3 axis of chondrocytes catabolism and anabolism plays a critical role in OA development. Our results suggest that circSLC7A2 may serve as a new therapeutic target for osteoarthritis.

摘要: Objectives: The final stage of liver development is the production of hepatocytes and cholangiocytes (biliary epithelial cells) from bipotent hepatic progenitor cells. We used HepaRG cells, which are bipotent and able to differentiate into both hepatocytes and cholangiocytes, as a model to study the action of a novel lncRNA (lnc-RHL) and its role in the regulation of bipotency leading to hepatocytes and cholangiocytes. Materials and Methods: Differentiation of HepaRG cells was assessed by marker expression and morphology which revealed their ability to differentiate into hepatocytes and cholangiocytes (modelling the behaviour of hepatoblasts in vivo). Using a qRT-PCR and RACE, we cloned a novel lncRNA (lnc-RHL; regulator of hepatic lineages) that is upregulated upon HepaRG differentiation. Using inducible knockdown of lnc-RHL concurrently with differentiation, we show that lnc-RHL is required for proper HepaRG cell differentiation resulting in diminution of the hepatocyte lineage. Results: Here, we report the discovery of lnc-RHL, a spliced and polyadenylated 670 base lncRNA expressed from the 11q23.3 apolipoprotein gene cluster. lnc-RHL expression is confined to hepatic lineages and is upregulated when bipotent HepaRG cells are caused to differentiate. HepaRG cells made deficient for lnc-RHL have reduced ability to differentiate into hepatocytes, but retain their ability to differentiate into cholangiocytes. Conclusions: Deficiency for lnc-RHL in HepaRG cells converts them from bipotent progenitor cells to unipotent progenitor cells with impaired ability to yield hepatocytes. We conclude that lnc-RHL is a key regulator of bipotency in HepaRG cells.

摘要: Objectives Abnormal expression of metabolic rate-limiting enzymes drives the occurrence and progression of hepatocellular carcinoma (HCC). This study aimed to elucidate the comprehensive model of metabolic rate-limiting enzymes associated with the prognosis of HCC. Materials and Methods HCC animal model and TCGA project were used to screen out differentially expressed metabolic rate-limiting enzyme. Cox regression, least absolute shrinkage and selection operation (LASSO) and experimentally verification were performed to identify metabolic rate-limiting enzyme signature. The area under the receiver operating characteristic curve (AUC) and prognostic nomogram were used to assess the efficacy of the signature in the three HCC cohorts (TCGA training cohort, internal cohort and an independent validation cohort). Results A classifier based on three rate-limiting enzymes (RRM1, UCK2 and G6PD) was conducted and serves as independent prognostic factor. This effect was further confirmed in an independent cohort, which indicated that the AUC at year 5 was 0.715 (95% CI: 0.653-0.777) for clinical risk score, whereas it was significantly increased to 0.852 (95% CI: 0.798-0.906) when combination of the clinical with signature risk score. Moreover, a comprehensive nomogram including the signature and clinicopathological aspects resulted in significantly predict the individual outcomes. Conclusions Our results highlighted the prognostic value of rate-limiting enzymes in HCC, which may be useful for accurate risk assessment in guiding clinical management and treatment decisions.