Wing polyphenism is an evolutionarily successful feature found in a wide range of insects. Long-winged morphs can fly, which allows them to escape adverse habitats and track changing resources, whereas short-winged morphs are flightless, but usually possess higher fecundity than the winged morphs. Studies on aphids, crickets and planthoppers have revealed that alternative wing morphs develop in response to various environmental cues, and that the response to these cues may be mediated by developmental hormones, although research in this area has yielded equivocal and conflicting results about exactly which hormones are involved. As it stands, the molecular mechanism underlying wing morph determination in insects has remained elusive. Here we show that two insulin receptors in the migratory brown planthopper Nilaparvata lugens, InR1 and InR2, have opposing roles in controlling long wing versus short wing development by regulating the activity of the forkhead transcription factor Foxo. InR1, acting via the phosphatidylinositol-3-OH kinase (PI(3)K)-protein kinase B (Akt) signalling cascade, leads to the long-winged morph if active and the short-winged morph if inactive. InR2, by contrast, functions as a negative regulator of the InR1-PI(3)K-Akt pathway: suppression of InR2 results in development of the long-winged morph. The brain-secreted ligand Ilp3 triggers development of long-winged morphs. Our findings provide the first evidence of a molecular basis for the regulation of wing polyphenism in insects, and they are also the first demonstration--to our knowledge--of binary control over alternative developmental outcomes, and thus deepen our understanding of the development and evolution of phenotypic plasticity.

Purpose: MicroRNAs (miRNA) are short noncoding RNAs that can play critical roles in diverse biological processes. They are implicated in tumorigenesis and function both as tumor suppressors and as oncogenes. The clinical significance of miRNA expression profiles in malignant gliomas remains unclear.Experimental Design: In this study, we examined the expression levels of 365 mature human miRNAs in 12 malignant gliomas, including 8 glioblastomas and 4 anaplastic astrocytomas, using TaqMan realtime quantitative PCR arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-196a, -196b, -21, and -15b, by analyzing 92 malignant gliomas by conventional real-time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 39 glioblastoma patients by Kaplan-Meier method and multivariate analysis.Results: Expression profiles in glioblastomas and anaplastic astrocytomas suggested that 16 miRNAs were candidate markers associated with the malignant progression of gliomas. Among them, miR-196a showed the most significant difference (P = 0.0038), with miR-196b also having a high significance (P = 0.0371). Both miRNAs showed increased expression levels in glioblastomas relative to both anaplastic astrocytomas and normal brains in the validation study. Furthermore, patients with high miR-196 expression levels showed significantly poorer survival by the Kaplan-Meier method (P = 0.0073). Multivariate analysis showed that miR-196 expression levels were an independent predictor of overall survival in all 39 glioblastoma patients (P = 0.021; hazard ratio, 2.81).Conclusions: Our results suggest that miR-196 may play a role in the malignant progression of gliomas and may be a prognostic predictor in glioblastomas. Clin Cancer Res; 16(16); 4289-97. ©2010 AACR.

The differently expressed lncRNAs may be associated with the pathogenesis of OA. Further functional studies are critical to confirming the function of lncRNAs in OA and to exploring new potential targets for therapy.

Highly efficient detection in the aqueous phase for water-insoluble organic molecule probes is challenging.T he bright aggregated-state electrochemiluminescence (ECL) of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles by ac o-reactant approach was discovered, and ah eterogeneous aggregationinduced emission ECL (HAIE-ECL) was constructed at the electrode surface,s howing very high ECL efficiency (37.8 %) and selective recognition for industrially important DNBP plasticizer with al ow detection limit of 0.15 nm in the water phase.Am echanistic study indicates that ECL is mainly generated due to the high electron affinity of siloles and restriction of the intramolecular motions caused by their propeller-like noncoplanar structures.T his system realizes the sensing of organic-based ECL in the water phase by solving the crucial problems of water insolubility and aggregationcaused quenching (ACQ), and demonstrates potential for further application because of its design and high efficiency.Scheme 1. Chemical structures of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles and 1,1-dimethyl-3,4-diphenyl-2,5-bis(trimethylsilyl)silole.

A major antiviral mechanism in plants is mediated by RNA silencing, which relies on the cleavage of viral dsRNA into virus-derived small interfering RNAs (vsiRNAs) by DICER-like enzymes. Members of the Argonaute (AGO) family of endonucleases then use these vsiRNA as guides to target viral RNA. This can result in a phenomenon known as recovery, whereby the plant silences viral gene expression and recovers from viral symptoms. Endogenous mRNAs can also be targeted by vsiRNAs in a phenomenon known as virus-induced gene silencing (VIGS). Although related to other RNA silencing mechanisms, it has not been established if recovery and VIGS are mediated by the same molecular mechanisms. We used tobacco rattle virus (TRV) carrying a fragment of the phytoene desaturase (PDS) gene (TRV-PDS) or expressing green fluorescent protein (TRV-GFP) as readouts for VIGS and recovery, respectively, in Arabidopsis ago mutants. Our results demonstrated roles for AGO2 and AGO4 in susceptibility to TRV, whereas VIGS of endogenous genes appeared to be largely mediated by AGO1. However, recovery appeared to be mediated by different components, as all the aforementioned mutants were able to recover from TRV-GFP inoculation. TRV RNAs from recovered plants associated less with ribosomes, suggesting that recovery involves translational repression of viral transcripts. Translationally repressed RNAs often accumulate in RNA processing bodies (PBs), where they are eventually processed by decapping enzymes. Consistent with this, we found that viral recovery induced increased PB formation and that a decapping mutant (DCP2) showed increased VIGS and virus RNA accumulation, indicating an important role for PBs in eliminating viral RNA.

Purpose: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease after long-term or high-dose glucocorticoid use. The pathogenesis of GIONFH is still controversial, and abnormal bone metabolism caused by glucocorticoids may be one of the important factors. Exosomes, owing to their positive effect on bone repair, show promising therapeutic effects on bone-related diseases. In this study, we hypothesised that exosomes reduce osteocyte apoptosis in rat GIONFH via the miR-21-PTEN-AKT signalling pathway.Methods: To evaluate the effects of exosomes in GIONFH, a dexamethasone-treated or exosome-treated in vitro cell model and a methylprednisolone-treated in vivo rat model were set up. In vitro, a CCK-8 assay and 5-ethynyl-2′-deoxyuridine staining were performed to evaluate the proliferation of osteocytes. Further, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, annexin V-fluorescein isothiocyanate-propidium iodide staining, and western blotting were conducted to evaluate the apoptosis of osteocytes. In vivo, we used micro-computed tomography and histological and immunohistochemical analyses to assess the effects of exosomes. Moreover, the mechanism of exosome action on osteocyte apoptosis through the miR-21-PTEN-AKT pathway was investigated by high-throughput RNA sequencing, fluorescence in situ hybridisation, luciferase reporter assays, and western blotting.Results: High-throughput RNA sequencing results showed that the AKT signalling pathway was up-regulated in the exosome group. Quantitative PCR and western blotting confirmed that the relative expression of genes in the AKT pathway was up-regulated. Western blotting revealed that AKT activated by exosomes inhibited osteocyte apoptosis. RNA fluorescence in situ hybridisation and luciferase reporter assays were performed to confirm the interaction between miR-21 and PTEN. According to the experiment in vivo, exosomes prevented GIONFH in a rat model as evidenced by micro-computed tomography scanning and histological and immunohistochemical analyses.Conclusions: Exosomes are effective at inhibiting osteocyte apoptosis (in MLO-Y4 cells) and at preventing rat GIONFH. These beneficial effects are mediated by the miR-21-PTEN-AKT signalling pathway.

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A novel mussel-inspired γ-PGA–DA tissue-adhesive hydrogel via a horseradish peroxidase-mediated reaction with robust tissue adhesive strength and hemostasis performance when wet.