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1.
Nature ; 519(7544): 464-7, 2015 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-25799997

RESUMO

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.


Assuntos
Hemípteros/anatomia & histologia , Hemípteros/metabolismo , Receptor de Insulina/metabolismo , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo , Animais , Feminino , Fatores de Transcrição Forkhead/deficiência , Fatores de Transcrição Forkhead/metabolismo , Hemípteros/enzimologia , Hemípteros/genética , Insulina/metabolismo , Masculino , Dados de Sequência Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/deficiência , Transdução de Sinais , Asas de Animais/anatomia & histologia , Asas de Animais/enzimologia
2.
Tumour Biol ; 36(6): 4689-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25619477

RESUMO

Low molecular weight heparin (LMWH) improving the cancer survival has been attracting attention for many years. Our previous study found that LMWH (Fraxiparine) strongly downregulated the invasive, migratory, and adhesive ability of human lung adenocarcinoma A549 cells. Here, we aimed to further identify the antitumor effects and possible mechanisms of Fraxiparine on A549 cells and human highly metastatic lung cancer 95D cells. The ability of cell invasion, migration, and adhesion were measured by Transwell, Millicell, and MTT assays. FITC-labeled phalloidin was used to detect F-actin bundles in cells. Chemotactic migration was analyzed in a modified Transwell assay. Measurement of protein expression and phosphorylation activity of PI3K, Akt, and mTOR was performed with Western blot. Our studies found that Fraxiparine significantly inhibited the invasive, migratory, and adhesive characteristics of A549 and 95D cells after 24 h incubation and showed a dose-dependent manner. Fraxiparine influenced the actin cytoskeleton rearrangement of A549 and 95D cells by preventing F-actin polymerization. Moreover, Fraxiparine could significantly inhibit CXCL12-mediated chemotactic migration of A549 and 95D cells in a concentration-dependent manner. Furthermore, Fraxiparine might destroy the interaction between CXCL12-CXCR4 axis, then suppress the PI3K-Akt-mTOR signaling pathway in lung cancer cells. For the first time, our data indicated that Fraxiparine could significantly inhibit the motility of lung cancer cells by restraining the actin cytoskeleton reorganization, and its related mechanism might be through inhibiting PI3K-Akt-mTOR signaling pathway mediated by CXCL12-CXCR4 axis. Therefore, Fraxiparine would be a potential drug for lung cancer metastasis therapy.


Assuntos
Adenocarcinoma/genética , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/biossíntese , Neoplasias Pulmonares/genética , Nadroparina/administração & dosagem , Receptores CXCR4/biossíntese , Citoesqueleto de Actina/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Adesão Celular/efeitos dos fármacos , Quimiocina CXCL12/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Receptores CXCR4/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Virol ; 86(21): 11941, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23043173

RESUMO

Bombyx mori nucleopolyhedrovirus (BmNPV), a member of the Baculoviridae, is a major pathogen of silkworm and has also been recently developed as an expression vector for heterologous gene expression in the silkworm larvae and pupae. To better understand the diversity of this important baculovirus, we sequenced the complete genome of the BmNPV strain isolated from India, where its host is available throughout the year due to its tropical climate. The genome of the Indian strain consists of 127,879 nucleotides, with a G+C content of 40.36%. There are 138 open reading frames (ORFs) encoding the predicted proteins of more than 50 amino acids. Genomic comparison of the Indian strain with 3 other reported BmNPV strains showed that the baculovirus repeat ORFs (bro) and homologous repeat regions (hr's) are highly variable. These results suggest that the BmNPV strain heterogeneity is mainly caused by single-nucleotide polymorphisms (SNPs) and changes in the hr's and bro genes.


Assuntos
DNA Viral/química , DNA Viral/genética , Genoma Viral , Nucleopoliedrovírus/genética , Animais , Composição de Bases , Bombyx/virologia , Índia , Dados de Sequência Molecular , Nucleopoliedrovírus/isolamento & purificação , Fases de Leitura Aberta , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
4.
Org Biomol Chem ; 11(7): 1242-50, 2013 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-23318505

RESUMO

Non-viral gene vectors play an important role in the development of gene therapy. In this report, different hydrophobic chains were introduced into low molecular weight (LMW) PEI-based biodegradable oligomers to form a series of lipopolymers (LPs), and their structure-activity relationships were studied. Results revealed that the nine polymers can condense plasmid DNA well to form nanoparticles with appropriate sizes (120-250 nm) and positive zeta-potentials (+25-40 V). In vitro experiments were carried out and it was found that LP2 showed much higher transfection efficiency both in the presence and in the absence of serum under the polymer/DNA weight ratio of 0.8 in A549 cells.


Assuntos
Antineoplásicos/farmacologia , DNA/farmacologia , Vetores Genéticos/farmacologia , Polietilenoimina/química , Polímeros/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , DNA/química , DNA/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Estrutura Molecular , Peso Molecular , Polietilenoimina/metabolismo , Polímeros/química , Polímeros/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
5.
Bioorg Med Chem ; 21(11): 3105-13, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23601818

RESUMO

A series of novel 1,4,7,10-tetraazacyclododecanes (cyclen)-based cationic lipids bearing histidine imidazole group 10a-10e were synthesized. These amphiphilic molecules have different hydrophobic tails (long chain, cholesterol or α-tocopherol) and various type of linking groups (ether, carbamate or ester). These molecules were used as non-viral gene delivery vectors, and their structure-activity relationships were investigated. As expected, the imidazole group could largely improve the buffering capabilities comparing to cyclen. The liposomes formed from 10 and dioleoylphosphatidyl ethanolamine (DOPE) could bind and condense plasmid DNA into nanoparticles with proper size and zeta-potentials. Comparing with Lipofectamine 2000, the formed lipoplexes gave lower transfected cells proportion, but higher fluorescence intensity, indicating their good intracellular delivering ability. Furthermore, results indicate that transfection efficiency of the cationic lipids is influenced by not only the hydrophobic tails but also the linking group. The cyclen-based cationic lipid with α-tocopherol hydrophobic tail and an ester linkage could give the highest transfection efficiency in the presence of serum.


Assuntos
Técnicas de Transferência de Genes , Compostos Heterocíclicos/química , Imidazóis/química , Lipídeos/síntese química , Tensoativos/síntese química , Cátions , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclamos , Corantes Fluorescentes , Genes Reporter , Proteínas de Fluorescência Verde , Humanos , Lipídeos/farmacologia , Estrutura Molecular , Nanopartículas/química , Plasmídeos/química , Plasmídeos/genética , Relação Estrutura-Atividade , Tensoativos/farmacologia , alfa-Tocoferol/química
6.
Ticks Tick Borne Dis ; 5(6): 864-70, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25150725

RESUMO

The tick Ixodes persulcatus is the predominant tick species in Northeastern China, and it is a major vector in transmission of tick-borne diseases. By 16S rRNA Illumina sequencing, we investigated the microbiome of I. persulcatus and assessed the variation of the microbiome before and after blood feeding. The prolonged blood meal dramatically altered the composition of the microbiome but did not influence the bacterial diversity. Overall, 373 and 289 bacterial genera were assigned to unfed and fed ticks, respectively. To investigate microbes that were potentially transmitted to vertebrate hosts during a blood meal, we examined the microbiome in rat blood after tick bites. Our data showed that 237 bacterial genera were suspected to be pathogens of vertebrates because they were commonly detected in unfed ticks, fed ticks, and rat blood samples after tick bites. Additionally, the prevalence survey on Borrelia burgdorferi s.l., Ehrlichia chaffeensis, Anaplasma phagocytophilum and Yersinia pestis was performed. We found that B. garinii and B. afzelii are the predominant genospecies of the Lyme disease spirochete in I. persulcatus ticks. This is the first time that the microbial composition in this tick species and in rat blood transmitted via tick bites has been reported. These data may ultimately assist in identification of novel pathogens transmitted by I. persulcatus ticks.


Assuntos
Vetores Aracnídeos/microbiologia , Borrelia burgdorferi/isolamento & purificação , Ixodes/microbiologia , Doença de Lyme/transmissão , Microbiota , Doenças Transmitidas por Carrapatos/transmissão , Animais , Borrelia burgdorferi/genética , China/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Doença de Lyme/epidemiologia , Doença de Lyme/microbiologia , Masculino , Prevalência , RNA Ribossômico 16S/genética , Ratos , Análise de Sequência de DNA , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia
7.
Genome Biol ; 15(12): 521, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25609551

RESUMO

BACKGROUND: The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts. RESULTS: We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal's exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host. CONCLUSIONS: Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.


Assuntos
Genoma de Inseto , Hemípteros/genética , Hemípteros/microbiologia , Herbivoria , Oryza/fisiologia , Adaptação Biológica , Animais , Artrópodes/genética , Ásia , Bactérias/genética , Evolução Molecular , Genômica , Hemípteros/fisiologia , Especificidade de Hospedeiro , Dados de Sequência Molecular , Família Multigênica , Filogenia , Homologia de Sequência do Ácido Nucleico , Simbiose
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