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1.
Materials (Basel) ; 14(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361383

RESUMO

A multi-scale fatigue analysis method for braided ceramic matrix composites (CMCs) based on sub-models is developed in this paper. The finite element shape function is used as the interpolation function for transferring the displacement information between the macro-scale and meso-scale models. The fatigue failure criterion based on the shear lag theory is used to implement the coupling calculation of the meso-scale and micro-scale. Combining the meso-scale cell model and the fatigue failure criterion based on the shear lag theory, the fatigue life of 2D SiC/SiC is analyzed. The analysis results are in good agreement with the experimental results, which proves the accuracy of the meso-scale cell model and the fatigue life calculation method. A multi-scale sub-model fatigue analysis method is used to study the fatigue damage of 2D SiC/SiC stiffened plates under random tension-tension loads. The influence of the sub-models at different positions in the macro-model element on the analysis results was analyzed. The results shows that the fatigue analysis method proposed in this paper takes into account the damage condition of the meso-structured of composite material, and at the same time has high calculation efficiency, and has low requirements for modeling of the macro finite element model, which can be better applied to the fatigue analysis of CMCs structure.

2.
Addict Biol ; 25(2): e12739, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31056833

RESUMO

Cocaine is a common abused drug that can induce abnormal synaptic and immune responses in the central nervous system (CNS). High mobility group box 1 (HMGB1) is one kind of inflammatory molecules that is expressed both on neurons and immune cells. Previous studies of HMGB1 in the CNS have largely focused on immune function, and the role of HMGB1 in neurons and cocaine addiction remains unknown. Here, we show that cocaine exposure induced the translocation and release of HMGB1 in the nucleus accumbens (NAc) neurons. Gain and loss of HMGB1 in the NAc bidirectionally regulate cocaine-induced conditioned place preference. From the nucleus to the cytosol, HMGB1 binds to glutamate receptor subunits (GluA2/GluN2B) on the membrane, which regulates cocaine-induced synaptic adaptation and the formation of cocaine-related memory. These data unveil the role of HMGB1 in neurons and provide the evidence for the HMGB1 involvement in drug addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/genética , Proteína HMGB1/genética , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Recompensa , Animais , Cocaína/farmacologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Modelos Animais de Doenças , Masculino , Núcleo Accumbens/fisiopatologia , Ratos , Ratos Sprague-Dawley
3.
Appl Environ Microbiol ; 85(3)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446553

RESUMO

In subduction zones, serpentinization and biological processes may release alkanes to the deep waters, which would probably result in the rapid spread of Alcanivorax However, the timing and area of the alkane distribution and associated enrichment of alkane-degrading microbes in the dark world of the deep ocean have not been explored. In this study, we report the richness (up to 17.8%) of alkane-degrading bacteria, represented by Alcanivorax jadensis, in deep water samples obtained at 3,000 to 6,000 m in the Mariana Trench in two cruises. The relative abundance of A. jadensis correlated with copy numbers of functional almA and alkB genes, which are involved in alkane degradation. In these water samples, we detected a high flux of alkanes, which probably resulted in the prevalence of A. jadensis in the deep waters. Contigs of A. jadensis were binned from the metagenomes for examination of alkane degradation pathways and deep sea-specific pathways, which revealed a lack of nitrate and nitrite dissimilatory reduction in our A. jadensis strains. Comparing the results for the two cruises conducted close to each other, we suggest periodic release of alkanes that may spread widely but periodically in the trench. Distribution of alkane-degrading bacteria in the world's oceans suggests the periodic and remarkable contributions of Alcanivorax to the deep sea organic carbon and nitrogen sources.IMPORTANCE In the oligotrophic environment of the Mariana Trench, alkanes as carbohydrates are important for the ecosystem, but their spatial and periodic spreading in deep waters has never been reported. Alkane-degrading bacteria such as Alcanivorax spp. are biological signals of the alkane distribution. In the present study, Alcanivorax was abundant in some waters, at depths of up to 6,000 m, in the Mariana Trench. Genomic, transcriptomic, and chemical analyses provide evidence for the presence and activities of Alcanivorax jadensis in deep sea zones. The periodic spreading of alkanes, probably from the subductive plates, might have fundamentally modified the local microbial communities, as well as perhaps the deep sea microenvironment.


Assuntos
Alcanivoraceae/metabolismo , Alcanos/metabolismo , Água do Mar/microbiologia , Alcanivoraceae/classificação , Alcanivoraceae/genética , Alcanivoraceae/isolamento & purificação , Alcanos/análise , Biodegradação Ambiental , Ecossistema , Nitratos/metabolismo , Nitritos/metabolismo , Filogenia , Água do Mar/química
4.
Appl Environ Microbiol ; 84(1)2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054873

RESUMO

Protective symbiosis has been reported in many organisms, but the molecular mechanisms of the mutualistic interactions between the symbionts and their hosts are unclear. Here, we sequenced the 424-kbp genome of "Candidatus Spiroplasma holothuricola," which dominated the hindgut microbiome of a sea cucumber, a major scavenger captured in the Mariana Trench (6,140 m depth). Phylogenetic relationships indicated that the dominant bacterium in the hindgut was derived from a basal group of Spiroplasma species. In this organism, the genes responsible for the biosynthesis of amino acids, glycolysis, and sugar transporters were lost, strongly suggesting endosymbiosis. The highly decayed genome consists of two chromosomes and harbors genes coding for proteolysis, microbial toxin, restriction-methylation systems, and clustered regularly interspaced short palindromic repeats (CRISPRs), composed of three cas genes and 76 CRISPR spacers. The holothurian host is probably protected against invading viruses from sediments by the CRISPRs/Cas and restriction systems of the endosymbiotic spiroplasma. The protective endosymbiosis indicates the important ecological role of the ancient Spiroplasma symbiont in the maintenance of hadal ecosystems.IMPORTANCE Sea cucumbers are major inhabitants in hadal trenches. They collect microbes in surface sediment and remain tolerant against potential pathogenic bacteria and viruses. This study presents the genome of endosymbiotic spiroplasmas in the gut of a sea cucumber captured in the Mariana Trench. The extreme reduction of the genome and loss of essential metabolic pathways strongly support its endosymbiotic lifestyle. Moreover, a considerable part of the genome was occupied by a CRISPR/Cas system to provide immunity against viruses and antimicrobial toxin-encoding genes for the degradation of microbes. This novel species of Spiroplasma is probably an important protective symbiont for the sea cucumbers in the hadal zone.


Assuntos
Genoma Bacteriano , Pepinos-do-Mar/microbiologia , Spiroplasma/genética , Simbiose , Animais , Oceano Pacífico , Filogenia , Análise de Sequência de DNA , Spiroplasma/fisiologia
5.
BMC Med Genomics ; 10(1): 55, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28874147

RESUMO

BACKGROUND: Inhibition of nonsense-mediated mRNA decay (NMD) in tumor cells can suppress tumor growth through expressing new antigens whose mRNAs otherwise are degraded by NMD. Thus NMD inhibition is a promising approach for developing cancer therapies. Apparently, the success of this approach relies on the basal NMD activity in cancer cells. If NMD is already strongly inhibited in tumors, the approach would not work. Therefore, it is crucial to assess NMD activity in cancers to forecast the efficacy of NMD-inhibition based therapy. METHODS: Here we develop three metrics using RNA-seq data to measure NMD activity, and apply them to a dataset consisting of 72 lung cancer (adenocarcinoma) patients. RESULTS: We show that these metrics have good correlations, and that the NMD activities in adenocarcinoma samples vary among patients: some cancerous samples show significantly stronger NMD activities than the normal tissues while some others show the opposite pattern. The variation of NMD activities among these samples may be partly explained by the varying expression of NMD effectors. CONCLUSIONS: In sum, NMD activity varies among lung cancerous samples, which forecasts varying efficacies of NMD-inhibition based therapy. The developed metrics can be further used in other cancer types to assess NMD activity.


Assuntos
Neoplasias Pulmonares/genética , Degradação do RNAm Mediada por Códon sem Sentido/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Éxons/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA
6.
Biomed Res Int ; 2016: 4895476, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27243032

RESUMO

Nowadays, pollution levels are rapidly increasing all over the world. One of the most important pollutants is PM2.5. It is known that the pollution environment may cause several problems, such as greenhouse effect and acid rain. Among them, the most important problem is that pollutants can induce a number of serious diseases. Some studies have reported that PM2.5 is an important etiologic factor for lung cancer. In this study, we extensively investigate the associations between PM2.5 and 22 disease classes recommended by Goh et al., such as respiratory diseases, cardiovascular diseases, and gastrointestinal diseases. The protein-protein interactions were used to measure the linkage between disease genes and genes that have been reported to be modulated by PM2.5. The results suggest that some diseases, such as diseases related to ear, nose, and throat and gastrointestinal, nutritional, renal, and cardiovascular diseases, are influenced by PM2.5 and some evidences were provided to confirm our results. For example, a total of 18 genes related to cardiovascular diseases are identified to be closely related to PM2.5, and cardiovascular disease relevant gene DSP is significantly related to PM2.5 gene JUP.


Assuntos
Doença , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/química , Mapeamento de Interação de Proteínas/métodos , Poluentes Atmosféricos/efeitos adversos , Predisposição Genética para Doença , Humanos
7.
Biochim Biophys Acta ; 1860(11 Pt B): 2750-5, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27266344

RESUMO

Genomic alterations in DNA can cause human cancer. DNA copy number variants (CNV), as one of the types of DNA mutations, have been considered to be associated with various human cancers. CNVs vary in size from 1bp up to one complete chromosome arm. In order to understand the difference between different human cancers on CNVs, in this study, we developed a method to computationally classify six human cancer types by using only CNV level values. The CNVs of 23,082 genes were used as features to construct the classifier. Then the features are carefully selected by mRMR (minimum Redundancy Maximum Relevance Feature Selection) and IFS (Incremental Feature Selection) methods. An accuracy of over 0.75 was reached by using only the CNVs of 19 genes based on Dagging method in 10-fold cross validation. It was indicated that these 19 genes may play important roles in differentiating cancer types. We also analyzed the biological functions of several top genes within the 19 gene list. The statistical results and biological analysis of these genes from this work might further help understand different human cancer types and provide guidance for related validation experiments. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.


Assuntos
Variações do Número de Cópias de DNA/genética , Neoplasias/genética , Cromossomos/genética , Genômica/métodos , Humanos , Mutação/genética
8.
J Genet Genomics ; 42(8): 423-36, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26336799

RESUMO

Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs (lincRNAs) play in diverse cellular processes, our knowledge of how lincRNAs function in cancer remains sparse. Here, we present a comprehensive landscape of RNA-seq transcriptome profiles of lung adenocarcinomas and their paired normal counterparts to unravel gene regulation rules of lincRNAs. Consistent with previous findings of co-expression between neighboring protein-coding genes, lincRNAs were typically co-expressed with their neighboring genes, which was found in both cancerous and normal tissues. By building a mathematical model based on correlated gene expression, we distinguished an additional subset of lincRNAs termed "regulatory lincRNAs", representing their dominant roles in gene regulation. The number of regulatory lincRNAs was significantly higher in cancerous compared to normal tissues, and most of them positively regulated protein-coding genes in trans. Functional validation, using knockdown, determined that regulatory lincRNA, GAS5, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory lincRNAs with inclusion of some cancer-associated lincRNAs. Our integrated analysis reveals enhanced regulatory effects of lincRNAs and provides a resource for the study of regulatory lincRNAs that play critical roles in lung adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Regulação da Expressão Gênica , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Análise de Sequência de RNA , Adenocarcinoma de Pulmão , Biomarcadores Tumorais/metabolismo , Humanos , Modelos Teóricos , RNA Longo não Codificante/química , RNA Nucleolar Pequeno/metabolismo , Transcriptoma
9.
Biomed Res Int ; 2015: 964795, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874234

RESUMO

Thyroid cancer is a typical endocrine malignancy. In the past three decades, the continued growth of its incidence has made it urgent to design effective treatments to treat this disease. To this end, it is necessary to uncover the mechanism underlying this disease. Identification of thyroid cancer-related genes and chemicals is helpful to understand the mechanism of thyroid cancer. In this study, we generalized some previous methods to discover both disease genes and chemicals. The method was based on shortest path algorithm and applied to discover novel thyroid cancer-related genes and chemicals. The analysis of the final obtained genes and chemicals suggests that some of them are crucial to the formation and development of thyroid cancer. It is indicated that the proposed method is effective for the discovery of novel disease genes and chemicals.


Assuntos
Bases de Dados Genéticas , Ligantes , Neoplasias da Glândula Tireoide/genética , Algoritmos , Descoberta de Drogas , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
10.
PLoS One ; 10(3): e0123147, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25822500

RESUMO

Gathering vast data sets of cancer genomes requires more efficient and autonomous procedures to classify cancer types and to discover a few essential genes to distinguish different cancers. Because protein expression is more stable than gene expression, we chose reverse phase protein array (RPPA) data, a powerful and robust antibody-based high-throughput approach for targeted proteomics, to perform our research. In this study, we proposed a computational framework to classify the patient samples into ten major cancer types based on the RPPA data using the SMO (Sequential minimal optimization) method. A careful feature selection procedure was employed to select 23 important proteins from the total of 187 proteins by mRMR (minimum Redundancy Maximum Relevance Feature Selection) and IFS (Incremental Feature Selection) on the training set. By using the 23 proteins, we successfully classified the ten cancer types with an MCC (Matthews Correlation Coefficient) of 0.904 on the training set, evaluated by 10-fold cross-validation, and an MCC of 0.936 on an independent test set. Further analysis of these 23 proteins was performed. Most of these proteins can present the hallmarks of cancer; Chk2, for example, plays an important role in the proliferation of cancer cells. Our analysis of these 23 proteins lends credence to the importance of these genes as indicators of cancer classification. We also believe our methods and findings may shed light on the discoveries of specific biomarkers of different types of cancers.


Assuntos
Neoplasias/metabolismo , Proteínas/metabolismo , Biologia Computacional/métodos , Humanos , Análise Serial de Proteínas/métodos , Proteoma/metabolismo
11.
Glia ; 63(3): 483-96, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25377529

RESUMO

Microglia, the major immune cells in central nervous system, act as the surveillance and scavenger of immune defense and inflammatory response. Previous studies suggest that there might be close relationship between acid-sensing ion channels (ASICs) and inflammation, however, the exact role of ASICs in microglia during inflammation remains elusive. In the present study, we identified the existence of ASICs in the primary cultured rat microglia and explored their functions. By using reverse transcriptase polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), western blotting, and immunofluorescence experiments, we demonstrated that ASIC1, ASIC2a, and ASIC3 were existed in cultured and in situ rat microglia. After lipopolysaccharide (LPS) stimulation, the expressions of microglial ASIC1 and ASIC2a were upregulated. Meanwhile, ASIC-like currents and acid-induced elevation of intracellular calcium were increased, which could be inhibited by the nonspecific ASICs antagonist amiloride and specific homomeric ASIC1a blocker PcTx1. In addition, both inhibitors reduced the expression of inflammatory cytokines, including inducible nitric oxide synthase and cyclooxygenase 2 stimulated by LPS. Furthermore, we also observed significant increase in the expression of ASIC1 and ASIC2a in scrape-stimulated microglial migration. Amiloride and PcTx1 prevented the migration by inhibiting ERK phosphorylation. Taken together, these results suggest that ASICs participate in neuroinflammatory response, which will provide a novel therapeutic strategy for controlling the inflammation-relevant neuronal diseases.


Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Movimento Celular/fisiologia , Inflamação/metabolismo , Microglia/fisiologia , Bloqueadores do Canal Iônico Sensível a Ácido/farmacologia , Animais , Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Potenciais da Membrana/fisiologia , Microglia/efeitos dos fármacos , Estimulação Física , RNA Mensageiro/metabolismo , Ratos
12.
Nucleic Acids Res ; 42(22): 13969-80, 2014 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-25428370

RESUMO

Numerous eukaryotic genes are alternatively spliced. Recently, deep transcriptome sequencing has skyrocketed proportion of alternatively spliced genes; over 95% human multi-exon genes are alternatively spliced. One fundamental question is: are all these alternative splicing (AS) events functional? To look into this issue, we studied the most common form of alternative 5' splice sites-GYNNGYs (Y = C/T), where both GYs can function as splice sites. Global analyses suggest that splicing noise (due to stochasticity of splicing process) can cause AS at GYNNGYs, evidenced by higher AS frequency in non-coding than in coding regions, in non-conserved than in conserved genes and in lowly expressed than in highly expressed genes. However, ∼20% AS GYNNGYs in humans and ∼3% in mice exhibit tissue-dependent regulation. Consistent with being functional, regulated GYNNGYs are more conserved than unregulated ones. And regulated GYNNGYs have distinctive sequence features which may confer regulation. Particularly, each regulated GYNNGY comprises two splice sites more resembling each other than unregulated GYNNGYs, and has more conserved downstream flanking intron. Intriguingly, most regulated GYNNGYs may tune gene expression through coupling with nonsense-mediated mRNA decay, rather than encode different proteins. In summary, AS at GYNNGY 5' splice sites is primarily splicing noise, and secondarily a way of regulation.


Assuntos
Processamento Alternativo , Sítios de Splice de RNA , Animais , Sequência de Bases , Sequência Conservada , Humanos , Macaca mulatta , Camundongos , Especificidade de Órgãos
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