Opioid and Notch signaling pathways are reciprocally regulated through miR- 29a and miR-212 expression

Background

The abuse of opioids, such as morphine and phentanyl or other drugs as heroin is a social and health problem that affects an increasing number of people each year. The activation of the mu opioid receptor triggers several molecular changes that alter the expression of diverse genes, including miRNAs. The dysregulation of these molecules could explain some of the developmental alterations that are induced after drug intake. In addition, the Notch signaling cascade has also been related to alterations on these processes.

<Emphasis Type="Italic">Zingiber officinale</Emphasis> extends <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> life span in xenobiotic-induced oxidative stress conditions

Background

The possibility of dietary ginger to enhance oxidative stress resistance and to extend life span was studied on Drosophila melanogaster.

Methods

Oxidative stress was induced by a reducing agent dithiothreitol. Experimental groups of male D. melanogaster were cultured on media containing: 1) no additive; 2) dithiothreitol, added into the nutritional mixture to the final concentration of 10 mM; 3) 25 mg of ginger powder g^–1 of the nutritional mixture; and 4) 10 mM of dithiothreitol and 25 mg of ginger powder g^–1 of the nutritional mixture. The number of alive fruit flies was inspected daily, and mean life span was determined for each experimental group.

Results

The addition of dithiothreitol to D. melanogaster nutritional mixture was established to result in an increase in concentration of two markers of oxidative stress conditions (thiobarbituric acid reactive substances as products of lipid peroxidation and carbonylated proteins as products of protein oxidation) in fly tissues. It was followed by significant reduction of mean life span and maximum life span of the last 10% of flies. Plant preparation, being added simultaneously with dithiothreitol, significantly diminished the negative effects of this xenobiotic. In conditions of additional stress load induced by hydrogen peroxide or high temperature, survival of insects treated with dithiothreitol on the background of ginger powder was the highest.

Conclusions

Thus, the presented data give the evidence that ginger preparations can reduce oxidative stress outcomes and significantly increase the life expectancy of fruit flies in stress conditions.

     

Molecular mechanism of Arabidopsis thaliana profilins as antifungal proteins

Background

It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms.

IgG glycosylation and DNA methylation are interconnected with smoking

Background

Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic.

Stabilization of G-quadruplex structure on vascular endothelial growth factor gene promoter depends on CpG methylation site and cation type

Background

DNA methylation at the 5-position of cytosine is an epigenetic modification of CpG dinucleotides. In addition to CpG methylation, the G-quadruplex (G4) structure has been reported as a regulator of gene expression. The identification of G4 forming sequences in CpG islands suggests an involvement of CpG-methylated G4 structures in biological processes; however, few reports have addressed the effects of CpG methylation on G4 structure.

Overexpression of human Argonaute2 inhibits cell and tumor growth

Background

Argonaute (Ago) proteins are essential for the biogenesis and function of ~ 20–30 nucleotide long RNAs such as microRNAs (miRNAs). Ago expression increases or decreases under various physiological conditions, although the functional consequences are unknown. In addition, while reduced global miRNA production was shown to enhance cellular transformation and tumorigenesis, how Ago proteins contribute to human diseases has not been reported.

Method

Ago2, an essential Ago isoform in mammals, was stably expressed in 293 T, the human embryonic kidney cell line, and H1299, the human lung adenocarcinoma cell line. miRNA and mRNA expression was investigated by quantitative PCR and microarray profiling. Cell proliferation and migration was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay in the cell cultures, respectively. How Ago2 affected cell growth in vivo was determined by H1299 xenograft tumor growth in mice. Changes in Ago2 expression in human lung cancer samples were investigated by quantitative PCR and immunohistochemistry.

Results

Stable Ago2 overexpression elicited specific changes in miRNA and mRNA expression in both 293 T and H1299 cells. It also inhibited cell proliferation and migration in cell cultures as well as xenograft tumor growth in nude mice. Ago2 expression was lower in human lung adenocarcinomas than in the paired, non-cancerous tissues.

General significance

We concluded that changes in Ago2 expression might have significant physiological and pathological consequences in vivo.     

A combined literature and in silico analysis enlightens the role of the NDRG family in the gut

Background

The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse.

Mutations of acetylcholinesterase which confer insecticide resistance in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> populations

Background

Organophosphate and carbamate insecticides irreversibly inhibit acetylcholinesterase causing death of insects. Resistance-modified acetylcholinesterases(AChEs) have been described in many insect species and sequencing of their genes allowed several point mutations to be described. However, their relative frequency and their cartography had not yet been addressed.

Results

To analyze the most frequent mutations providing insecticide resistance in Drosophila melanogaster acetylcholinesterase, the Ace gene was cloned and sequenced in several strains harvested from different parts of the world. Sequence comparison revealed four widespread mutations, I161V, G265A, F330Y and G368A. We confirm here that mutations are found either isolated or in combination in the same protein and we show that most natural populations are heterogeneous, composed of a mixture of different alleles. In vitro expression of mutated proteins showed that combining mutations in the same protein has two consequences: it increases resistance level and provides a wide spectrum of resistance.

Conclusion

The presence of several alleles in natural populations, offering various resistance to carbamate and organophosphate compounds will complicate the establishment of resistance management programs.

     

Novel link prediction for large-scale miRNA-lncRNA interaction network in a bipartite graph

Background

Current knowledge and data on miRNA-lncRNA interactions is still limited and little effort has been made to predict target lncRNAs of miRNAs. Accumulating evidences suggest that the interaction patterns between lncRNAs and miRNAs are closely related to relative expression level, forming a titration mechanism. It could provide an effective approach for characteristic feature extraction. In addition, using the coding non-coding co-expression network and sequence data could also help to measure the similarities among miRNAs and lncRNAs. By mathematically analyzing these types of similarities, we come up with two findings that (i) lncRNAs/miRNAs tend to collaboratively interact with miRNAs/lncRNAs of similar expression profiles, and vice versa, and (ii) those miRNAs interacting with a cluster of common target genes tend to jointly target at the common lncRNAs.

Methods

In this work, we developed a novel group preference Bayesian collaborative filtering model called GBCF for picking up a top-k probability ranking list for an individual miRNA or lncRNA based on the known miRNA-lncRNA interaction network.

Results

To evaluate the effectiveness of GBCF, leave-one-out and k-fold cross validations as well as a series of comparison experiments were carried out. GBCF achieved the values of area under ROC curve of 0.9193, 0.8354+/??0.0079, 0.8615+/??0.0078, and 0.8928+/??0.0082 based on leave-one-out, 2-fold, 5-fold, and 10-fold cross validations respectively, demonstrating its reliability and robustness.

Conclusions

GBCF could be used to select potential lncRNA targets of specific miRNAs and offer great insights for further researches on ceRNA regulation network.

     

Potential role for Ext1-dependent heparan sulfate in regulating P311 gene expression in A549 carcinoma cells

Background

Exostosin-1 (EXT1), a member of the EXT protein family, is indispensable for synthesis of heparan sulfate (HS) chains that bind to and modulate the signaling efficiency of numerous growth factor activities. We have previously shown that Ext1 mutated mouse embryonic fibroblasts produce short sulfated HS chains which dramatically influence tumor cell behavior in a 3-dimensional (3D) heterospheroid system composed of tumor cells and fibroblasts.

Silencing of <Emphasis Type="Italic">Mythimna separata chitinase</Emphasis> genes via oral delivery of <Emphasis Type="Italic">in planta</Emphasis>-expressed RNAi effectors from a recombinant plant virus

Objectives

To evaluate transient expression of RNA interference (RNAi) effectors in Nicotiana benthamiana plants by using recombinant virus vectors and also oral delivery of the effectors for silencing of Mythimna separata endogenous gene expression.

Results

Mythimna separata is a serious pest of corn production in China. To evaluate RNAi approaches to target specific RNAs in M. separate, we cloned fragments of the M. separata chitinase sequences into a virus vector in order to produce RNAi effectors during virus infection and replication in plants. When the infected plants were fed to M. separata, expression levels of target MseChi1 and MseChi2 genes were down-regulated by 76 and 45 %, respectively, and sequence-specific siRNAs were detected in recipient insects. RNAi-based silencing of chitinase genes also led to body weight decreases by 43 %.

Conclusion

Our research demonstrates target mRNA knockdown and suggests a promising application for controlling of M. separata by in planta expression of RNAi effectors using a recombinant plant virus.

     

Modulation of Mcl-1 transcription by serum deprivation sensitizes cancer cells to cisplatin

Background

The development of approaches that increase therapeutic effects of anti-cancer drugs is one of the most important tasks of oncology. Caloric restriction in vivo or serum deprivation (SD) in vitro has been shown to be an effective tool for sensitizing cancer cells to chemotherapeutic drugs. However, the detailed mechanisms underlying the enhancement of apoptosis in cancer cells by SD remain to be elucidated.

Metabolic profiling of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> metamorphosis: a new insight into the central metabolic pathways

Introduction

Metamorphosis is a complicated process in which cell proliferation, differentiation, and death are orchestrated to form the mature structures of insects. In Drosophila, this process is controlled by ecdysone, a steroid hormone responsible for tissue remodeling and organogenesis that gives rise to the adult fly.

Objective

By using a metabolomics approach, this study aimed to elucidate global changes in the central metabolic pathways in Drosophila throughout metamorphosis and then further examine the effects of temperature and origin on metabolic profiles.

Methods

Targeted and non-targeted metabolic profiling of time-course samples from Drosophila were constructed to cover a wide range of cellular metabolites during metamorphosis.

Results

This was the first wide-scale metabolomics study of Drosophila metamorphosis focusing on central metabolism. The abundance of detected metabolites changed drastically and correlated strongly with the development of Drosophila pupae. In non-stress conditions, temperature affected the developmental time, but the metabolic state at a certain stage of metamorphosis remained stable. Between D. melanogaster Canton S and Oregon R, similar metabolic profiles throughout metamorphosis was observed. However, there were still differences in purine and pyrimidine metabolism at an early stage in the pupal period, which was matched by differences in ecdysteroid levels.

Conclusion

This study supported the strength of metabolomics in the field of developmental biology. The results provided a general view on the metabolic profile of Drosophila during metamorphosis, which provides basic 3 knowledge for future metabolomics studies using Drosophila.