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1.
Appl Opt ; 58(12): 3293-3300, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31044809

RESUMO

In this paper, we propose a high-resolution terahertz coded-aperture imaging method with fast beam scanning for near-field three-dimensional targets. This method utilizes a coded aperture to modulate incident terahertz waves randomly and drive the terahertz beam to scan the entire imaging space step by step. Theoretical analyses based on physical optics are performed, and simulation experiments are implemented to demonstrate the feasibility of the proposed method.

2.
Mol Ther Oncolytics ; 14: 82-93, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31024988

RESUMO

Lung cancer is one of the leading causes of cancer-associated death, with the etiology largely unknown. The aim of this study was to identify key driver genes with therapeutic potentials in lung adenocarcinoma (LUAD). Transcriptome microarray data from four GEO datasets (GEO: GSE7670, GSE10072, GSE68465, and GSE43458) were jointly analyzed for differentially expressed genes (DEGs). Ontologic analysis showed that most of the upregulated DEGs enriched in collagen catabolic and fibril organization processes were regulated by matrix metalloproteinases (MMPs). Matrix metalloproteinase 11 (MMP11), the highest upregulated MMP family member in LUAD-transformed cells, acted in an autocrine manner and was significantly increased in sera of LUAD patients. MMP11 depletion severely impaired LUAD cell proliferation, migration, and invasion in vitro, in line with retarded tumor growth in xenograft models. Treatment of different human LUAD cell lines with anti-MMP11 antibody significantly retarded cell growth and migration. Administration of anti-MMP11 antibody at a dose of 1 µg/g body weight significantly suppressed tumor growth in xenograft models. These findings indicate that MMP11 is a key cancer driver gene in LUAD and is an appealing target for antibody therapy.

3.
J Mol Graph Model ; 89: 131-138, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30884450

RESUMO

The iridium(III) complexes could be excellent second-order nonlinear optical (NLO) switch materials due to various advantages including abundant valence states, the diversity of coordination forms and rich electrochemical properties. In this work, the substituent effect and the multi-state switchable response of a series of novel Ir(CˆN)2ADC complexes (CˆN = cyclometalated ligands and ADC = diaminocarbene), induced by electrochemical behavior, have been calculated by density functional theory. The results show that the introducing strong electron-withdrawing groups on ADC ligands significantly enhanced the static first hyperpolarizabilities (ßtot). Moreover, a distinct improvement of the ßtot values can be found from the neutral complexes to the corresponding redox states. By this way, the remarkable multi-state NLO switch can be achieved. Remarkably, the ßtot values of the one-electron-oxidized complex 1+ and the one-electron-reduced complex 1- are ∼5.4 and ∼12.7 times larger than the corresponding neutral complex 1, respectively. The larger ßtot values are attributed to the lower transition energy and remarkable bathochromic shift of maximal absorption wavelength, which can be further illustrated by the separate distribution of ß density. We envision that these studied iridium complexes can be seen as versatile and novel second-order NLO switching materials.

4.
BMC Bioinformatics ; 19(1): 401, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390627

RESUMO

BACKGROUND: Identifying cancer biomarkers from transcriptomics data is of importance to cancer research. However, transcriptomics data are often complex and heterogeneous, which complicates the identification of cancer biomarkers in practice. Currently, the heterogeneity still remains a challenge for detecting subtle but consistent changes of gene expression in cancer cells. RESULTS: In this paper, we propose to adaptively capture the heterogeneity of expression across samples in a gene regulation space instead of in a gene expression space. Specifically, we transform gene expression profiles into gene regulation profiles and mathematically formulate gene regulation probabilities (GRPs)-based statistics for characterizing differential expression of genes between tumor and normal tissues. Finally, an unbiased estimator (aGRP) of GRPs is devised that can interrogate and adaptively capture the heterogeneity of gene expression. We also derived an asymptotical significance analysis procedure for the new statistic. Since no parameter needs to be preset, aGRP is easy and friendly to use for researchers without computer programming background. We evaluated the proposed method on both simulated data and real-world data and compared with previous methods. Experimental results demonstrated the superior performance of the proposed method in exploring the heterogeneity of expression for capturing subtle but consistent alterations of gene expression in cancer. CONCLUSIONS: Expression heterogeneity largely influences the performance of cancer biomarker identification from transcriptomics data. Models are needed that efficiently deal with the expression heterogeneity. The proposed method can be a standalone tool due to its capacity of adaptively capturing the sample heterogeneity and the simplicity in use. SOFTWARE AVAILABILITY: The source code of aGRP can be downloaded from https://github.com/hqwang126/aGRP .


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Neoplasias/genética , Simulação por Computador , Perfilação da Expressão Gênica , Humanos , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos , Probabilidade , Análise de Sequência de RNA , Software , Transcriptoma
5.
Environ Pollut ; 242(Pt A): 778-787, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30031311

RESUMO

It has generally been assumed that the immobilization of U(VI) via polyphosphate accumulating microorganisms may present a sink for uranium, but the potential mechanisms of the process and the stability of precipitated uranium under aerobic conditions remain elusive. This study seeks to explore the mechanism, capacity, and stability of uranium precipitation under aerobic conditions by a purified indigenous bacteria isolated from acidic tailings (pH 6.5) in China. The results show that over the treatment ranges investigated, maximum removal of U(VI) from aqueous solution was 99.82% when the initial concentration of U(VI) was 42 µM, pH was 3.5, and the temperature was with 30 °C much higher than that of other reported microorganisms. The adsorption mechanism was elucidated via the use of SEM-EDS, XPS and FTIR. SEM-EDS showed two peaks of uranium on the surface. A plausible explanation for this, supported by FTIR, is that uranium precipitated on the biosorbent surfaces. XPS measurements indicated that the uranium product is most likely a mixture of 13% U(VI) and 87% U(IV). Notably, the reoxidation experiment found that the uranium precipitates were stable in the presence of Ca2+ and Mg2+, however, U(IV) is oxidized to U(VI) in the presence of NO3- and Na+ ions, resulting in rapid dissolution. It implies that the synthesized Leifsonia sp. coated biochar could be utilized as a green and effective biosorbent. However, it may not a good choice for in-situ remediation due to the subsequent re-oxidation under aerobic conditions. These observations can be of some guiding significance to the application of the bioremediation technology in surface environments.


Assuntos
Biodegradação Ambiental , Carvão Vegetal/química , Poluentes Radioativos do Solo/análise , Urânio/análise , Adsorção , China , Íons , Oxirredução , Poluentes Radioativos do Solo/química , Temperatura Ambiente , Urânio/química
6.
Genes (Basel) ; 9(7)2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954150

RESUMO

Although a number of methods have been proposed for identifying differentially expressed pathways (DEPs), few efforts consider the dynamic components of pathway networks, i.e., gene links. We here propose a signaling dynamics detection method for identification of DEPs, DynSig, which detects the molecular signaling changes in cancerous cells along pathway topology. Specifically, DynSig relies on gene links, instead of gene nodes, in pathways, and models the dynamic behavior of pathways based on Markov chain model (MCM). By incorporating the dynamics of molecular signaling, DynSig allows for an in-depth characterization of pathway activity. To identify DEPs, a novel statistic of activity alteration of pathways was formulated as an overall signaling perturbation score between sample classes. Experimental results on both simulation and real-world datasets demonstrate the effectiveness and efficiency of the proposed method in identifying differential pathways.

7.
IET Syst Biol ; 11(6): 174-181, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29125126

RESUMO

Inferring gene regulatory networks (GRNs) from gene expression data is an important but challenging issue in systems biology. Here, the authors propose a dictionary learning-based approach that aims to infer GRNs by globally mining regulatory signals, known or latent. Gene expression is often regulated by various regulatory factors, some of which are observed and some of which are latent. The authors assume that all regulators are unknown for a target gene and the expression of the target gene can be mapped into a regulatory space spanned by all the regulators. Specifically, the authors modify the dictionary learning model, k-SVD, according to the sparse property of GRNs for mining the regulatory signals. The recovered regulatory signals are then used as a pool of regulatory factors to calculate a confidence score for a given transcription factor regulating a target gene. The capability of recovering hidden regulatory signals was verified on simulated data. Comparative experiments for GRN inference between the proposed algorithm (OURM) and some state-of-the-art algorithms, e.g. GENIE3 and ARACNE, on real-world data sets show the superior performance of OURM in inferring GRNs: higher area under the receiver operating characteristic curves and area under the precision-recall curves.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Biologia de Sistemas , Regulação da Expressão Gênica , Curva ROC
8.
BMC Bioinformatics ; 18(1): 375, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28830341

RESUMO

BACKGROUND: Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal. RESULTS: This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis. CONCLUSIONS: Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.


Assuntos
Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Modelos Estatísticos , Neoplasias/diagnóstico , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA/química , RNA/metabolismo , Análise de Sequência de RNA
9.
J Biomed Inform ; 73: 104-114, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28756161

RESUMO

Identifying differentially expressed pathways (DEPs) plays important roles in understanding tumor etiology and promoting clinical treatment of cancer or other diseases. By assuming gene expression to be a sparse non-negative linear combination of hidden pathway signals, we propose a pathway crosstalk-based transcriptomics data analysis method (ctPath) for identifying differentially expressed pathways. Biologically, pathways of different functions work in concert at the systematic level. The proposed method interrogates the crosstalks between pathways and discovers hidden pathway signals by mapping high-dimensional transcriptomics data into a low-dimensional pathway space. The resulted pathway signals reflect the activity level of pathways after removing pathway crosstalk effect and allow a robust identification of DEPs from inherently complex and noisy transcriptomics data. CtPath can also correct incomplete and inaccurate pathway annotations which frequently occur in public repositories. Experimental results on both simulation data and real-world cancer data demonstrate the superior performance of ctPath over other popular approaches. R code for ctPath is available for non-commercial use at the URL http://micblab.iim.ac.cn/Download/.


Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Expressão Gênica , Humanos , Neoplasias , Transdução de Sinais
10.
J Phys Chem A ; 120(46): 9330-9340, 2016 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-27934245

RESUMO

Zwitterionic complexes have been the subject of great interest in the past several decades due to their multifunctional application in supramolecular chemistry. Herein, a series of internally stable charge-compensated carboranylated square-planar Pt(II) zwitterionic complexes have been explored by density functional theory aim to assessing their structures, the first hyperpolarizabilities, first hyperpolarizability densities, and electronic absorption spectra. It is found that the first hyperpolarizabilities of two-dimensional (2D) structure complexes are much larger with respect to the one-dimensional complex. It is ascribed to the lower transition energy and more obvious charge transfer, which can be further illustrated by their large amplitude and separate distribution of first hyperpolarizability density. In addition, the first hyperpolarizabilities of 2D complexes can be further significantly modified by introducing electron-donating/withdrawing groups on the carborane cage. As a consequence, we believe that these 2D zwitterionic complexes can behave as novel second-order nonlinear optical chromophore with a promising future.

11.
IET Syst Biol ; 10(6): 252-259, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27879480

RESUMO

Inferring gene regulatory networks (GRNs) from microarray expression data are an important but challenging issue in systems biology. In this study, the authors propose a Bayesian information criterion (BIC)-guided sparse regression approach for GRN reconstruction. This approach can adaptively model GRNs by optimising the l1-norm regularisation of sparse regression based on a modified version of BIC. The use of the regularisation strategy ensures the inferred GRNs to be as sparse as natural, while the modified BIC allows incorporating prior knowledge on expression regulation and thus avoids the overestimation of expression regulators as usual. Especially, the proposed method provides a clear interpretation of combinatorial regulations of gene expression by optimally extracting regulation coordination for a given target gene. Experimental results on both simulation data and real-world microarray data demonstrate the competent performance of discovering regulatory relationships in GRN reconstruction.


Assuntos
Escherichia coli/genética , Redes Reguladoras de Genes , Saccharomyces cerevisiae/genética , Biologia de Sistemas , Algoritmos , Área Sob a Curva , Teorema de Bayes , Biologia Computacional , Simulação por Computador , Bases de Dados Factuais , Perfilação da Expressão Gênica , Curva ROC , Análise de Regressão
12.
J Mol Graph Model ; 67: 111-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27262529

RESUMO

Carborane has been the subject of great interest over the last decades due to its high structural, chemical, biological stability and diverse applications. In the present work, carboranyl-substituted indole/indoline compounds and their functionalized derivatives have been systematically investigated by density functional theory (DFT) method with the view of assessing their electronic structures and first hyperpolarizabilities. Significantly, the first hyperpolarizabilities can be obviously enhanced by the introduction of a strong electron-withdrawing group for closed-ring forms, while the strong electron-donating group is beneficial for large first hyperpolarizabilities for open-ring forms. It indicates that the NLO properties of these compounds can be enhanced by controlling their relative substituent groups. Furthermore, the time-dependent DFT calculation illustrates that the enhancement of the first hyperpolarizabilities are found due to the obvious charge transfer (CT) transition, and closed-ring forms have a significant difference on the CT patterns versus open-ring ones. Investigation of the structure-property relationship and substituent effects at the molecular level can benefit for further exploration of carboranyl-substituted indole/indoline derivatives with versatile and fascinating NLO properties.


Assuntos
Compostos de Boro/química , Indóis/química , Dinâmica não Linear , Fenômenos Ópticos , Modelos Moleculares , Teoria Quântica , Eletricidade Estática , Fatores de Tempo
13.
IET Syst Biol ; 9(4): 147-54, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26243831

RESUMO

This study proposes a gene link-based method for survival time-related pathway hunting. In this method, the authors incorporate gene link information to estimate how a pathway is associated with cancer patient's survival time. Specifically, a gene link-based Cox proportional hazard model (Link-Cox) is established, in which two linked genes are considered together to represent a link variable and the association of the link with survival time is assessed using Cox proportional hazard model. On the basis of the Link-Cox model, the authors formulate a new statistic for measuring the association of a pathway with survival time of cancer patients, referred to as pathway survival score (PSS), by summarising survival significance over all the gene links in the pathway, and devise a permutation test to test the significance of an observed PSS. To evaluate the proposed method, the authors applied it to simulation data and two publicly available real-world gene expression data sets. Extensive comparisons with previous methods show the effectiveness and efficiency of the proposed method for survival pathway hunting.


Assuntos
Biomarcadores Tumorais/análise , Mineração de Dados/métodos , Neoplasias/metabolismo , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Ligação Genética , Humanos , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Taxa de Sobrevida
14.
Zhonghua Nan Ke Xue ; 21(2): 119-23, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25796683

RESUMO

OBJECTIVE: To observe the influence of different concentrations of bisphenol A (BPA) on glucose metabolism and lactate dehydrogenase (LDH) expression in rat Sertoli cells in vitro and investigate the mechanisms of BPA inducing male infertility. METHODS: Using two-step enzyme digestion, we isolated Sertoli cells from male Wistar rats and constructed a primary Sertoli cell system, followed by immunohistochemical FasL staining. We randomly divided the Sertoli cells into a control group to be cultured in the serum-free minimal essential medium (MEM) plus dimethyl sulfoxide (DMSO) and three experimental groups to be treated with 100 nmol/L, 10 µmol/L, and 1 mmol/L BPA, respectively, in the MEM plus DMSO. After 48 hours of treatment, we measured the proliferation of the cells by CCK-8 assay, determined the concentrations of metabolites by NMR spectroscopy, and detected the expression of LDH in the Sertoli cells by RT-PCR and Western blot. RESULTS: The purity of the isolated Sertoli cells was (96.05 ± 1.28)% (n = 10). Compared with the control group, the 100 nmol/L, 10 µmol/L, and 1 mmol/L BPA groups showed no remarkable changes in the proliferation of Sertoli cells ([98 ± 8]%, [96 ± 3]%, and [95 ± 3]%, P >0.05), but the 10 µmol/L and 1 mmol/L of BPA groups exhibited significantly decreased concentrations of intracellular glucose ([3.89 ± 0.07] vs [3.36 ± 0.24] and [3.04 ± 0.21] pmol/cell, P <0.05) and lactate ([0.43 ± 0.06] vs [0.29 ± 0.05] and [0.20 ± 0.03] pmol/cell, P <0.05). The expression of LDH mRNA was decreased with the increased concentration of BPA, while that of LDH protein reduced only in the 1 mmol/L BPA group (P <0.05). CONCLUSION: High-concentration BPA decreases the expression of LDH and alters glucose metabolism in Sertoli cells, and therefore may reduce the provision of lactate for germ cells and impair spermatogenesis.


Assuntos
Compostos Benzidrílicos/farmacologia , Glucose/metabolismo , L-Lactato Desidrogenase/metabolismo , Fenóis/farmacologia , Células de Sertoli/efeitos dos fármacos , Animais , Compostos Benzidrílicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultura Livres de Soro , Dimetil Sulfóxido/farmacologia , Técnicas In Vitro , Infertilidade Masculina/induzido quimicamente , Masculino , Fenóis/administração & dosagem , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Células de Sertoli/metabolismo , Espermatogênese/efeitos dos fármacos
15.
Indian J Orthop ; 49(6): 577-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26806962

RESUMO

BACKGROUND: Post traumatic osteonecrosis of a vertebral body occurring in a delayed fashion was first described by the German doctor Kümmell in 1895. Several studies have reported percutaneous vertebroplasty (PVP), or percutaneous kyphoplasty (PKP) for Kümmell's disease achieves good outcomes. However, it is unknown whether a technique is superior for the treatment of this disease. The objective of the study is to compare the efficacy of PVP and PKP for the treatment of Kümmell's disease. MATERIALS AND METHODS: A retrospective review was conducted for 73 patients with Kümmell's disease. PVP was performed in 38 patients and PKP in 35 patients. Visual analogue score (VAS) was used to evaluate pain. The anterior vertebral height was measured. The operative time, the incidence of cement leakage and the costs were recorded. RESULTS: In both PVP group and PKP group, the VAS and anterior vertebral height significantly improved at 1-day postoperatively (P < 0.05), and the improvement sustained at the final followup (P > 0.05). Between the PVP and PKP groups, there were no significant differences in VAS and the anterior vertebral height at 1-day postoperatively and at the final followup (P > 0.05). The operating time and expense in the PKP group were higher than the PVP group (P < 0.001). Cement leakages in the PKP group were fewer than PVP group (P < 0.05). CONCLUSIONS: PVP is a faster, less expensive option that still provides a comparable pain relief and restoration of vertebral height to PKP for the treatment of Kümmell's disease. PKP has a significant advantage over PVP in term of the fewer cement leakages.

16.
Bioinformatics ; 31(4): 572-80, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25411328

RESUMO

MOTIVATION: Tremendous amount of omics data being accumulated poses a pressing challenge of meta-analyzing the heterogeneous data for mining new biological knowledge. Most existing methods deal with each gene independently, thus often resulting in high false positive rates in detecting differentially expressed genes (DEG). To our knowledge, no or little effort has been devoted to methods that consider dependence structures underlying transcriptomics data for DEG identification in meta-analysis context. RESULTS: This article proposes a new meta-analysis method for identification of DEGs based on joint non-negative matrix factorization (jNMFMA). We mathematically extend non-negative matrix factorization (NMF) to a joint version (jNMF), which is used to simultaneously decompose multiple transcriptomics data matrices into one common submatrix plus multiple individual submatrices. By the jNMF, the dependence structures underlying transcriptomics data can be interrogated and utilized, while the high-dimensional transcriptomics data are mapped into a low-dimensional space spanned by metagenes that represent hidden biological signals. jNMFMA finally identifies DEGs as genes that are associated with differentially expressed metagenes. The ability of extracting dependence structures makes jNMFMA more efficient and robust to identify DEGs in meta-analysis context. Furthermore, jNMFMA is also flexible to identify DEGs that are consistent among various types of omics data, e.g. gene expression and DNA methylation. Experimental results on both simulation data and real-world cancer data demonstrate the effectiveness of jNMFMA and its superior performance over other popular approaches. AVAILABILITY AND IMPLEMENTATION: R code for jNMFMA is available for non-commercial use via http://micblab.iim.ac.cn/Download/. CONTACT: hqwang@ustc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Metilação de DNA , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Simulação por Computador , Humanos , Neoplasias Pulmonares/genética , Metanálise como Assunto
17.
Biomed Res Int ; 2014: 375980, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24982873

RESUMO

With the development of next-generation DNA sequencing technologies, large-scale cancer genomics projects can be implemented to help researchers to identify driver genes, driver mutations, and driver pathways, which promote cancer proliferation in large numbers of cancer patients. Hence, one of the remaining challenges is to distinguish functional mutations vital for cancer development, and filter out the unfunctional and random "passenger mutations." In this study, we introduce a modified method to solve the so-called maximum weight submatrix problem which is used to identify mutated driver pathways in cancer. The problem is based on two combinatorial properties, that is, coverage and exclusivity. Particularly, we enhance an integrative model which combines gene mutation and expression data. The experimental results on simulated data show that, compared with the other methods, our method is more efficient. Finally, we apply the proposed method on two real biological datasets. The results show that our proposed method is also applicable in real practice.


Assuntos
Algoritmos , Simulação por Computador , Mutação/genética , Neoplasias/genética , Transdução de Sinais/genética , Genes Neoplásicos , Humanos , Neoplasias Pulmonares/genética , Cadeias de Markov , Método de Monte Carlo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo
18.
Cancer Immunol Immunother ; 63(9): 911-24, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24893855

RESUMO

BACKGROUND: Cancer vaccines reproducibly cure laboratory animals and reveal encouraging trends in brain tumor (glioma) patients. Identifying parameters governing beneficial vaccine-induced responses may lead to the improvement of glioma immunotherapies. CD103(+) CD8 T cells dominate post-vaccine responses in human glioma patients for unknown reasons, but may be related to recent thymic emigrant (RTE) status. Importantly, CD8 RTE metrics correlated with beneficial immune responses in vaccinated glioma patients. METHODS: We show by flow cytometry that murine and human CD103(+) CD8 T cells respond better than their CD103(-) counterparts to tumor peptide-MHC I (pMHC I) stimulation in vitro and to tumor antigens on gliomas in vivo. RESULTS: Glioma responsive T cells from mice and humans both exhibited intrinsic de-sialylation-affecting CD8 beta. Modulation of CD8 T cell sialic acid with neuraminidase and ST3Gal-II revealed de-sialylation was necessary and sufficient for promiscuous binding to and stimulation by tumor pMHC I. Moreover, de-sialylated status was required for adoptive CD8 T cells and lymphocytes to decrease GL26 glioma invasiveness and increase host survival in vivo. Finally, increased tumor ST3Gal-II expression correlated with clinical vaccine failure in a meta-analysis of high-grade glioma patients. CONCLUSIONS: Taken together, these findings suggest that de-sialylation of CD8 is required for hyper-responsiveness and beneficial anti-glioma activity by CD8 T cells. Because CD8 de-sialylation can be induced with exogenous enzymes (and appears particularly scarce on human T cells), it represents a promising target for clinical glioma vaccine improvement.


Assuntos
Antígenos CD/imunologia , Neoplasias Encefálicas/terapia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/farmacologia , Células Dendríticas/imunologia , Glioma/terapia , Cadeias alfa de Integrinas/imunologia , Animais , Antígenos CD/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Feminino , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/terapia , Glioma/imunologia , Glioma/metabolismo , Humanos , Imunoterapia Adotiva/métodos , Cadeias alfa de Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neuraminidase/metabolismo , Neuraminidase/farmacologia , Sialiltransferases/metabolismo , Sialiltransferases/farmacologia
19.
Huan Jing Ke Xue ; 35(4): 1215-22, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24946567

RESUMO

The variations of black carbon (BC) mass concentration in Shanghai are analyzed and discussed by using hourly averaged data monitored continuously at Shanghai Urban Environmental Meteorological Center from January 2008 to December 2012. The results show that the annual mean mass concentration of BC decreased from (4 045.3 +/- 3 375.4) ng x m(-3) in 2008 to (2 766.2 +/- 2 078.9) ng x m(-3) in 2012, and the annual changes are 2.3%, - 6.5%, -18.7% and -12.1%, respectively. The yearly averaged BC mass concentration in Shanghai is on the low side of middle-level compared with other mega-cities of China. According to the test data,the highest monthly averaged concentration of BC appeared in November and December,which were 5 426.6 ng x m(-3) and 5 365.3 ng x m(-3), respectively,and then in January, June and October, which were 4402.5, 3763.3 and 3412.7 ng x m(-3), respectively. The diurnal cycles of the BC mass concentration show that there are two obvious peaks during morning 07:00-10:00 and during evening 18:00-22:00 Beijing time (BT), and the first peak was higher than the second on weekdays, but opposite on weekends and holidays. The daily mean mass concentration of BC was 9% higher on weekdays than on weekends and holidays. In addition, an empirical equation is obtained for daily BC concentration estimation and prediction using all the effective test data during the 5-year observation period and employing the regression analysis.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Fuligem/análise , Carbono/análise , China , Cidades , Estações do Ano
20.
J Exp Bot ; 65(15): 4191-200, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24803501

RESUMO

The diversity of phenylpropanoids offers a rich inventory of bioactive chemicals that can be exploited for plant improvement and human health. Recent evidence suggests that glycosylation may play a role in the partitioning of phenylpropanoid precursors for a variety of downstream uses. This work reports the functional characterization of a stress-responsive glycosyltransferase, GT1-316 in Populus. GT1-316 belongs to the UGT84A subfamily of plant glycosyltransferase family 1 and is designated UGT84A17. Recombinant protein analysis showed that UGT84A17 is a hydroxycinnamate glycosyltransferase and able to accept a range of unsubstituted and substituted cinnamic and benzoic acids as substrates in vitro. Overexpression of GT1-316 in transgenic Populus led to plant-wide increases of hydroxycinnamoyl-glucose esters, which were further elevated under N-limiting conditions. Levels of the two most abundant flavonoid glycosides, rutin and kaempferol-3-O-rutinoside, decreased, while levels of other less abundant flavonoid and phenylpropanoid conjugates increased in leaves of the GT1-316-overexpressing plants. Transcript levels of representative phenylpropanoid pathway genes were unchanged in transgenic plants, supporting a glycosylation-mediated redirection of phenylpropanoid carbon flow as opposed to enhanced phenylpropanoid pathway flux. The metabolic response of N-replete transgenic plants overlapped with that of N-stressed wild types, as the majority of phenylpropanoid derivatives significantly affected by GT1-316 overexpression were also significantly changed by N stress in the wild types. These results suggest that UGT84A17 plays an important role in phenylpropanoid metabolism by modulating biosynthesis of hydroxycinnamoyl-glucose esters and their derivatives in response to developmental and environmental cues.


Assuntos
Ácidos Cumáricos/metabolismo , Glicosiltransferases/metabolismo , Hidroxibenzoatos/metabolismo , Populus/enzimologia , Estresse Fisiológico , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Populus/genética
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