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The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) late expression factor gene lef-10 has been identified to be required for viral late gene expression by transient expression assay. Our previous work has shown that the gene product LEF-10 can form very stable high-molecular-weight complexes, but the structure and function of the protein remain unknown. In this study, we demonstrated that LEF-10 was essential for the replication of AcMNPV, and its truncated fragment containing amino acid residues 1 to 48 were sufficient to support the virus survival. Our data also suggested that the LEF-10 could spontaneously aggregate to form punctate spots in virus infected Sf9 cells at low frequency, and the aggregation of the protein could be induced by LEF-10 over-expression. When the protein aggregated to form punctate spots, soluble LEF-10 proteins were depleted and this could result in the down-regulation of viral late gene expression. [ABSTRACT FROM AUTHOR]

Extraordinary variation has been found in mitochondrial (mt) genome inheritance, gene content and arrangement among bivalves. However, only few bivalve mt genomes have been comparatively analyzed to infer their evolutionary scenarios. In this study, the complete mt genome of the venerid Paphia euglypta (Bivalvia: Veneridae) was firstly studied and, secondly, it was comparatively analyzed with other venerids (e.g., Venerupis philippinarum and Meretrix petechialis) to better understand the mt genome evolution within a family. Though several common features such as the AT content, codon usage of protein-coding genes, and AT/GC skew are shared by the three venerids, a high level of variability is observed in genome size, gene content, gene order, arrangements and primary sequence of nucleotides or amino acids. Most of the gene rearrangement can be explained by the 'tandem duplication and random loss' model. From the observed rearrangement patterns, we speculate that block interchange between adjacent genes may be common in the evolution of mt genomes in venerids. Furthermore, this study presents several new findings in mt genome annotation of V. philippinarum and M. petechialis, and hence we have reannotated the genome of these two species as: (1) the ORF of the formerly annotated cox2 gene in V. philippinarum is deduced by using a truncated 'T' codon and a second cox2 gene is identified; (2) the trnS-AGN gene is identified and marked in the mt genome of both venerids. Thus, this study demonstrated a high variability of mt genomes in the Veneridae, and showed the importance of comparative mt genome analysis to interpret the evolution of the bivalve mt genome. Une variation extraordinaire a été observée en ce qui a trait à la transmission, au contenu génique et à l'arrangement du génome mitochondrial (mt) chez les bivalves. Cependant, seuls quelques génomes mt ont été comparés chez les bivalves pour en comprendre l'évolution. Dans ce travail, le génome mt complet du Vénéridé Paphia euglypta (Bivalvia : Veneridae) a été étudié et ensuite comparé à ceux d'autres Vénéridés (e.g., Venerupis philippinarum et Meretrix petechialis) afin de mieux comprendre l'évolution du génome mt au sein d'une famille. Bien que plusieurs caractéristiques étaient semblables chez les trois Vénéridés, comme le contenu en AT, l'usage des codons au sein des régions codant pour des protéines et le biais AT/GC, une grande variabilité a été observée en ce qui a trait à la taille du génome, le contenu et l'ordre génique, l'arrangement et la séquence primaire des nucléotides ou des acides aminés. La plupart des réarrangements géniques pouvaient s'expliquer via le modèle de « duplication en tandem suivie d'une perte aléatoire ». À partir des réarrangements observés, les auteurs proposent que l'échange de blocs entre gènes adjacents pourrait être un phénomène répandu dans l'évolution des génomes mt chez les Vénéridés. De plus, cette étude présente plusieurs nouvelles trouvailles en matière d'annotation des génomes mt chez le V. philippinarum et le M. petechialis. Les auteurs ont ainsi produit une nouvelle annotation du génome mt de ces deux espèces avec les modifications suivantes : 1) l'ORF du gène précédemment annoté comme étant cox2 chez le V. philippinarum a été déduit en utilisant un codon « T » tronqué et un second gène cox2 a été identifié ; 2) et le gène trnS-AGN a été identifié et annoté dans les génomes mt des deux espèces. Ainsi, cette étude a montré la grande variabilité des génomes mt chez les Vénéridés et l'importance de l'analyse comparée des génomes mt pour déduire l'évolution du génome mt chez les bivalves. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most frequently diagnosed histological subtype of lung cancer. Our purpose was to explore molecular subtypes and core genes for LUAD using multi-omics analysis.Methods: Methylation, transcriptome, copy number variation (CNV), mutations and clinical feature information concerning LUAD were retrieved from The Cancer Genome Atlas Database (TCGA). Molecular subtypes were conducted via the "iClusterPlus" package in R, followed by Kaplan-Meier survival analysis. Correlation between iCluster subtypes and immune cells was analyzed. Core genes were screened out by integration of methylation, CNV and gene expression, which were externally validated by independent datasets.Results: Two iCluster subtypes were conducted for LUAD. Patients in imprinting centre 1 (iC1) subtype had a poorer prognosis than those in iC2 subtype. Furthermore, iC2 subtype had a higher level of B cell infiltration than iC1 subtype. Two core genes including CNTN4 and RFTN1 were screened out, both of which had higher expression levels in iC2 subtype than iC1 subtype. There were distinct differences in CNV and methylation of them between two subtypes. After validation, low expression of CNTN4 and RFTN1 predicted poorer clinical outcomes for LUAD patients.Conclusion: Our findings comprehensively analyzed genomics, epigenomics, and transcriptomics of LUAD, offering novel underlying molecular mechanisms for LUAD. Two multi-omics-based core genes (CNTN4 and RFTN1) could become potential therapeutic targets for LUAD. [ABSTRACT FROM AUTHOR]

Summary: Global warming has profound impact on growth and development, and plants constantly adjust their internal circadian clock to cope with external environment. However, how clock‐associated genes fine‐tune thermoresponsive growth in plants is little understood.We found that loss‐of‐function mutation of REVEILLE5 (RVE5) reduces the expression of circadian gene EARLY FLOWERING 4 (ELF4) in Arabidopsis, and confers accelerated hypocotyl growth under warm‐temperature conditions.Both RVE5 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) accumulate at warm temperatures and bind to the same EE cis‐element presented on ELF4 promoter, but the transcriptional repression activity of RVE5 is weaker than that of CCA1. The binding of CCA1 to ELF4 promoter is enhanced in the rve5‐2 mutant at warm temperatures, and overexpression of ELF4 in the rve5‐2 mutant background suppresses the rve5‐2 mutant phenotype at warm temperatures.Therefore, the transcriptional repressor RVE5 finetunes ELF4 expression via competing at a cis‐element with the stronger transcriptional repressor CCA1 at warm temperatures. Such a competition–attenuation mechanism provides a balancing system for modulating the level of ELF4 and thermoresponsive hypocotyl growth under warm‐temperature conditions. See also the Commentary on this article by Balcerowicz, 237: 9–11. [ABSTRACT FROM AUTHOR]

The number of B cells is increased and the O-glycans of IgA1 are incompletely galactosylated in IgA nephropathy (IgAN). Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN. Patients with IgAN exhibit higher miR-374b in B cells compared to controls. We show that miR-374b targets PTEN and Cosmc by luciferase assays and western blot analysis. Inhibition of miR-374b increased PTEN and Cosmc expression, and prevented cell proliferation and aberrant glycosylation of IgA1, thus representing a new therapeutic approach for IgAN. [ABSTRACT FROM AUTHOR]

Euphorbia helioscopia L. is a traditional Chinese medicine; recently research found that its ethyl acetate extract (EAE) plays an important role on tumor cell proliferation, apoptosis, invasion, and metastasis in vitro. But the effect of EAE for tumor cells in vivo has not been reported. To explore the inhibitory effect of EAE and molecular mechanism on hepatocellular carcinoma (HCC) SMMC-7721 cells in vivo, we utilized the nude mouse xenograft model of HCC. Treated with EAE (50, 100, and 200 μg/mL), the volume of xenograft was measured during the entire process of EAE treatment. In EAE treatment group, the volume of xenograft was significantly reduced compared with the control group (P<0.05) and the protein expressions of CyclinD1, bcl-2, and MMP-9 were reduced, while those of bax, caspase-3, and nm23-H1 were increased. A significant change trend with increasing EAE concentrations has presented, compared with controls. Moreover, the ultrastructural morphology of xenografts showed significant changes, including nuclear pyknosis and chromatin condensation, We found that EAE could effectively inhibit tumor growth, induce apoptosis, and inhibit tumor invasion and metastasis in vivo; it is suggested that EAE is a potential candidate for as a new anticancer agent. [ABSTRACT FROM AUTHOR]