Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Brain Imaging Behav ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270776

RESUMO

Presbycusis, associated with a diminished quality of life characterized by bilateral sensorineural hearing loss at high frequencies, has become an increasingly critical public health problem. This study aimed to identify directed functional connectivity (FC) of the hippocampus in patients with presbycusis and to explore the causes if the directed functional connections of the hippocampus were disrupted. Presbycusis patients (n = 32) and age-, sex-, and education-matched healthy controls (n = 40) were included in this study. The seed regions of bilateral hippocampus were selected to identify directed FC in patients with presbycusis using Granger causality analysis (GCA) approach. Correlation analyses were conducted to detect the associations of disrupted directed FC of hippocampus with clinical measures of presbycusis. Compared to healthy controls, decreased directed FC between inferior parietal lobule, insula, right supplementary motor area, middle temporal gyrus and hippocampus were detected in presbycusis patients. Furthermore, a negative correlation between TMB score and the decline of directed FC from left inferior parietal lobule to left hippocampus (r = -0.423, p = 0.025) and from right inferior parietal lobule to right hippocampus (r = -0.516, p = 0.005) were also observed. The decreased directed functional connections of the hippocampus were detected in patients with presbycusis, which was associated with specific cognitive performance. This study mainly emphasizes the crucial role of hippocampus in presbycusis and will enhance our understanding of the neuropathological mechanisms of presbycusis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31284868

RESUMO

BACKGROUND: Glycogen synthase kinase-3 (GSK3) is associated with various key biological processes and has been considered as an important therapeutic target for the treatment of many diseases. Great efforts have been made on the development of GSK3 inhibitors, especially ATP-competitive GSK3ß inhibitor, but it is still a great challenge to develop selective GSK3ß inhibitors because of the high sequence homology with other kinases. OBJECTIVE: In order to reveal the selectivity mechanisms of GSK3ß inhibition at the molecular level, a series of ATP-competitive GSK3ß inhibitor was analyzed by a systematic computational method, combining 3D-QSAR, molecular docking, molecular dynamic simulations and free energy calculations. METHODS: Firstly, 3D-QSAR with CoMFA was built to explore the general structure activity relationships. Secondly, CDOCKER and Flexible docking were employed to predicted the reasonable docking poses of all studied inhibitors. And then, both GSK3ß and CDK2 complexes were selected to conduct molecular dynamics simulations. Finally, the free energy calculations were employed to find the key selective-residues. RESULTS: CoMFA model suggested the steric, hydrophobic fields play key roles in the bioactivities of inhibitors, and the binding mechanisms were well analyzed through molecular docking. The binding free energies predicted are in good agreement with the experimental bioactivities and the free energy calculations showed that the binding of GSK3ß/inhibitors was mainly contributed from hydrogen bonding and hydrophobic interaction. CONCLUSION: Some key residues for selective binding were highlighted, which may afford important guidance for the rational design of novel ATP-competitive GSK3ß inhibitors.

3.
IEEE Trans Cybern ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31329571

RESUMO

This paper concentrates on the linear least mean square (LLMS) filtered and smoothed estimators for networked linear stochastic systems. Multiple packet losses, Markovian communication constraints, and superposed process noise are considered simultaneously. In order to reduce the channel load during communication, at every step, just one transmission node is permitted to send data packets. Hence, a Markovian communication protocol is utilized to arrange the packets of these transmission nodes. Moreover, multiple data packet dropouts occur during transmission due to an imperfect communication channel. Therefore, the global observation information cannot be obtained by the state estimator. The real state of Markov chain is assumed to be unknown to the estimator except the transition probability matrix. By means of the innovation analysis approach and orthogonal projection principle, we design Kalman-like estimators in a recursive form. Finally, through simulation experiments, we verify the effectiveness and superiority of the designed algorithm.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31297712

RESUMO

In natural produced bacteria, ß-carotene hydroxylase (CrtZ) and ß-carotene ketolase (CrtW) convert ß-carotene into astaxanthin. To increase astaxanthin production in heterologous strain, simple and effective strategies based on the co-expression of CrtZ and CrtW were applied in E. coli. First, nine artificial operons containing crtZ and crtW genes from different sources were constructed and, respectively, introduced into E. coli ZF237T, a ß-carotene producing host. Among the nine resulting strains, five accumulated detectable amounts of astaxanthin ranging from 0.49 to 8.07 mg/L. Subsequently, the protein fusion CrtZ to CrtW using optimized peptide linkers further increased the astaxanthin production. Strains expressing fusion proteins with CrtZ rather than CrtW attached to the N-terminus accumulated much more astaxanthin. The astaxanthin production of the best strain ZF237T/CrtZAs-(GS)1-WBs was 127.6% and 40.2% higher than that of strains ZF237T/crtZAsWBs and ZF237T/crtZBsWPs, respectively. The strategies depicted here also will be useful for the heterologous production of other natural products.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30703039

RESUMO

A novel control strategy for synchronization control for network systems with communication constraints is presented in this paper. The dynamics of nodes in the network are nonidentical. The communication topology of network is weakly connected with communication constraints. The designed distributed controller for each node has two parts: reference generator (RG) and regulator. All RGs adopt the communication channels to exchange local information and track the target trajectory. Meanwhile, regulator can ensure that nonidentical node achieves synchronization with its RG. In order to reduce the communication frequency between node and its regulator, a sampled-date control strategy is utilized. The upper bound of the aperiodic sampling instants is calculated through the small-gain theorem, where the closed-loop system is equivalently formulated as the feedback interconnection of a linear time-invariant system and an integral sampled-data operator. Finally, some simulation results are given to demonstrate the effectiveness of the controller design strategy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30369455

RESUMO

This paper studies the synchronization issue of time-varying Markovian jump neural networks (NNs). The denial-of-service (DoS) attack is considered in the communication channel connecting master NNs and slave NNs. An observer is designed based on the measurements of master NNs transmitted over this unreliable channel to estimate their states. The deception attack is used to destroy the controller by changing the sign of the control signal. Then, the mixed-type attacks are expressed uniformly, and a synchronization error system is established using this function. A finite-horizon 2-l#x221E; performance is proposed, and sufficient conditions are derived to ensure that the synchronization error system satisfies this performance. The controllers are then obtained by a recursive linear matrix inequality algorithm. At last, a simulation result to show the feasibility of the developed results is given.

7.
IEEE Trans Cybern ; 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29993924

RESUMO

The problem of asynchronous and resilient filtering for discrete-time Markov jump neural networks subject to extended dissipativity is investigated in this paper. The modes of the designed resilient filter are assumed to run asynchronously with the modes of original Markov jump neural networks, which accord well with practical applications and are described through a hidden Markov model. Due to the fluctuation of the filter parameters, a resilient filter taking into account parameter uncertainty is adopted. Being different from the norm-bound type of uncertainty which has been studied in a considerable number of the existing literatures, the interval type of uncertainty is introduced so as to describe uncertain phenomenon more accurately. By means of convex optimal method, the gains of filter are derived to guarantee the stochastic stability and extended dissipativity of the filtering error system under the wave of the filter parameters. Considering the limited computing power of MATLAB solver, a relatively simple simulation is exploited to verify the effectiveness and merits of the theoretical findings where the relationships among optimal performance index, uncertain parameter σ, and asynchronous rate are revealed.

8.
IEEE Trans Cybern ; 48(4): 1253-1262, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28391218

RESUMO

In this paper, we investigate the synchronization for heterogeneous network subject to event-triggering communication. The designed controller for each node includes reference generator (RG) and regulator. The predicted value of relative information between intermittent communication can significantly reduce the transmitted information. Based on the event triggering strategy and time-dependent threshold, all RGs can exponentially track the target trajectory. Then by the action of regulator, each node synchronizes with its RG. Meanwhile, a positive lower bound is obtained for the interevent intervals. Numerical example is given to demonstrate the effectiveness of the proposed event triggering strategy.

9.
Biotechnol Lett ; 40(2): 393-398, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29236191

RESUMO

OBJECTIVES: To investigate the capacity of a genome-reduced Bacillus subtilis strain as chassis cell for acetoin production from xylose. RESULTS: To endow the genome-reduced Bacillus subtilis strain BSK814 with the ability to utilize xylose, we inserted a native xyl operon into its genome and deleted the araR gene. The resulting strain BSK814A2 produced 2.94 g acetoin/l from 10 g xylose/l, which was 39% higher than control strain BSK19A2. The deletion of the bdhA and acoA genes further improved xylose utilization efficiency and increased acetoin production to 3.71 g/l in BSK814A4. Finally, BSK814A4 produced up to 23.3 g acetoin/l from 50 g xylose/l, with a yield of 0.46 g/g xylose. Both the titer and yield were 39% higher than those of control strain BSK19A4. CONCLUSIONS: As a chassis cell, genome-reduced B. subtilis showed significantly improved capacity for the production of the overflow product acetoin from xylose compared with wild-type strain.


Assuntos
Acetoína/metabolismo , Bacillus subtilis/genética , Genoma Bacteriano/genética , Engenharia Metabólica/métodos , Xilose/metabolismo , Acetoína/análise , Bacillus subtilis/metabolismo , Redes e Vias Metabólicas , Xilose/análise
10.
IEEE Trans Cybern ; 47(1): 130-141, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26731784

RESUMO

In this paper, the problem of output synchronization is investigated for the heterogeneous network with an uncertain leader. It is assumed that parameter perturbations influence the nonidentical linear agents, whose outputs are controlled to track the output of an uncertain leader. Based on the hierarchical structure of the communication graph, a novel control scheme is proposed to guarantee the output synchronization. As there exist parameter uncertainties in the models of the agents, the internal model principle is used to gain robustness versus plant parameter uncertainties. Furthermore, as the precise model of the leader is also not available, the adaptive control principle is adopted to tune the parameters in the local controllers. The developed new technique is able to simultaneously handle uncertainties in the follower parameters as well as the leader parameters. The agents in the upper layers will be treated as the exosystems of the agents in the lower layers. The local controllers are constructed in a sequential order. It is shown that the output synchronization can be achieved globally asymptotically and locally exponentially. Finally, a simulation example is given to illustrate the effectiveness and potential of the theoretic results obtained.

11.
IEEE Trans Cybern ; 46(9): 2132-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26316291

RESUMO

This paper is concerned with the consensus of multiagent systems with nonlinear dynamics through the use of aperiodic sampled-data controllers, which are more flexible than classical periodic sampled-data controllers. By input delay approach, the resulting sampled-data system is reformulated as a continuous system with time-varying delay in the control input. A continuous Lyapunov functional, which captures the information on sampling pattern, together with the free-weighting matrix method, is then used to establish a sufficient condition for consensusability. For a more general case that the sampled-data controllers are subject to constant input delays, a novel discontinuous Lyapunov functional is introduced on the basis of the vector extension of Wirtinger's inequality. This functional can lead to simplified and efficient stability conditions for computation and optimization. Further results on the estimate of maximal allowable sampling interval upper bound is given as well. Numerical example is provided to show the effectiveness and merits of the proposed protocol.

12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(9): 3003-7, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30085494

RESUMO

For the influence of temperature drift of the spectral responsivity on the repeatability infrared spectral emissivity measurement system, a temperature drift correction method is proposed based on the polynomial fitting. By analyzing the function of detector output voltage depended on its temperature. After studying the functional relationship between the temperature and spectral responsivity of detector, the spectral response curve varies with temperature is fitted and get the fitting equation. Calculating the drift correction factor of spectral responsivity, the output voltage of infrared detector is corrected. The effect of spectral response drift on the output voltage of detector is eliminated. With the development of temperature drift correction device of spectral responsivity, the temperature drift curve of spectral response is measured. Compared to the exponential fitting, the fitting consistency of sixth-order polynomial curve is excellent. Because of the application of this method, the repeatability of spectral emissivity measurement system is improved.

13.
Sci Rep ; 5: 13435, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26306712

RESUMO

Regulating and ameliorating enzyme expression and activity greatly affects the performance of a given synthetic pathway. In this study, a new synthetic pathway for cis, cis-muconic acid (ccMA) production was reconstructed without exogenous induction by regulating the constitutive expression of the important enzyme catechol 1,2-dioxygenase (CatA). Next, new CatAs with significantly improved activities were developed to enhance ccMA production using structure-assisted protein design. Nine mutations were designed, simulated and constructed based on the analysis of the CatA crystal structure. These results showed that mutations at Gly72, Leu73 and/or Pro76 in CatA could improve enzyme activity, and the activity of the most effective mutant was 10-fold greater than that of the wild-type CatA from Acinetobacter sp. ADP1. The most productive synthetic pathway with a mutated CatA increased the titer of ccMA by more than 25%. Molecular dynamic simulation results showed that enlarging the entrance of the substrate-binding pocket in the mutants contributed to their increased enzyme activities and thus improved the performance of the synthetic pathway.


Assuntos
Catecol 1,2-Dioxigenase/metabolismo , Escherichia coli/fisiologia , Melhoramento Genético/métodos , Transdução de Sinais/fisiologia , Ácido Sórbico/análogos & derivados , Catecol 1,2-Dioxigenase/genética , Engenharia Metabólica/métodos , Engenharia de Proteínas/métodos , Ácido Sórbico/isolamento & purificação , Ácido Sórbico/metabolismo , Biologia Sintética/métodos
14.
Genome Res ; 24(7): 1209-23, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24985915

RESUMO

Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community.


Assuntos
Biologia Computacional/métodos , Drosophila melanogaster/genética , Perfilação da Expressão Gênica , Anotação de Sequência Molecular , Transcriptoma , Animais , Análise por Conglomerados , Drosophila melanogaster/classificação , Evolução Molecular , Éxons , Feminino , Genoma de Inseto , Humanos , Masculino , Motivos de Nucleotídeos , Filogenia , Matrizes de Pontuação de Posição Específica , Regiões Promotoras Genéticas , Edição de RNA , Sítios de Splice de RNA , Processamento de RNA , Reprodutibilidade dos Testes , Sítio de Iniciação de Transcrição
15.
Circ Cardiovasc Genet ; 7(3): 335-43, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24951659

RESUMO

BACKGROUND: Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits. METHODS AND RESULTS: The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with ≥1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency ≥1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test. CONCLUSIONS: We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci.


Assuntos
Envelhecimento/genética , Estudo de Associação Genômica Ampla , Cardiopatias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Variação Genética , Genômica , Cardiopatias/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Projetos de Pesquisa , Análise de Sequência de DNA
16.
J Natl Cancer Inst ; 106(4): dju052, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24681603

RESUMO

BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor-δ/ß (PPAR-d) is upregulated in human colorectal cancers, but its role in colonic tumorigenesis remains controversial. METHODS: We generated a novel mouse model of intestinally targeted PPAR-d overexpression to simulate PPAR-d upregulation in human colon carcinogenesis. Colon-specific PPAR-d overexpression was confirmed by real-time reverse transcription polymerase chain reaction, immunoblotting, and activity assays. Mice with and without targeted PPAR-d overexpression were tested for azoxymethane (AOM)-induced colonic tumorigenesis. Mouse whole-genome transcriptome microarray analyses were performed to identify PPAR-d target genes to promote tumorigenesis. We used linear models to test for PPAR-d overexpression trend effects on tumor multiplicity. All statistical tests were two-sided. RESULTS: Targeted PPAR-d overexpression markedly increased colonic tumor incidence (from 0 of 10 wild-type [WT] littermate mice to 9 of 10 mice [P < .001] in 2 FVB/N background mouse lines [villin-PPAR-d-1 and villin-PPAR-d-2] at a 5-mg/kg AOM dose) and multiplicity (number of tumors per mouse per mg/kg dose of AOM increased from 0.47 [95% confidence interval [CI] = 0.22 to 0.72] for the WT littermates to 2.15 [95% CI = 1.90 to 2.40] [P < .001] for the villin-PPAR-d-1 mice and from 0.44 [95% CI = 0.09 to 0.79] for the WT littermates to 1.91 [95% CI = 1.57 to 2.25] [P < .001] for the villin-PPAR-d-2 mice). PPAR-d overexpression reversed resistance to AOM-induced colonic tumorigenesis in C57BL/6 mice. PPAR-d overexpression modulated expression of several novel PPAR-d target genes in normal-appearing colonic epithelial cells of mice with PPAR-d overexpression in a pattern that matched the changes in colonic tumors. CONCLUSIONS: Our finding that PPAR-d upregulation profoundly enhances susceptibility to colonic tumorigenesis should impact the development of strategies of molecularly targeting PPAR-d in cancer and noncancerous diseases.


Assuntos
Neoplasias do Colo/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Azoximetano , Carcinógenos , Neoplasias do Colo/induzido quimicamente , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/metabolismo , PPAR beta/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Regulação para Cima
17.
Genome Res ; 24(7): 1193-208, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24714809

RESUMO

The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.


Assuntos
Drosophila melanogaster/genética , Variação Genética , Genoma de Inseto , Fenótipo , Animais , Cromatina/genética , Cromatina/metabolismo , Drosophila melanogaster/microbiologia , Feminino , Ligação Genética , Tamanho do Genoma , Estudo de Associação Genômica Ampla , Genótipo , Técnicas de Genotipagem , Sequenciamento de Nucleotídeos em Larga Escala , Mutação INDEL , Desequilíbrio de Ligação , Masculino , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Reprodutibilidade dos Testes
18.
Cancer Med ; 3(3): 472-84, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24634093

RESUMO

The expression of 15-lipoxygenase-1 (15-LOX-1) is downregulated in colon cancer and other major cancers, and 15-LOX-1 reexpression in cancer cells suppresses colonic tumorigenesis. Various lines of evidence indicate that 15-LOX-1 expression suppresses premetastatic stages of colonic tumorigenesis; nevertheless, the role of 15-LOX-1 loss of expression in cancer epithelial cells in metastases continues to be debated. Hypoxia, a common feature of the cancer microenvironment, promotes prometastatic mechanisms such as the upregulation of hypoxia-inducible factor (HIF)-1α, a transcriptional master regulator that enhances cancer cell metastatic potential, angiogenesis, and tumor cell invasion and migration. We have, therefore, tested whether restoring 15-LOX-1 in colon cancer cells affects cancer cells' hypoxia response that promotes metastasis. We found that 15-LOX-1 reexpression in HCT116, HT29LMM, and LoVo colon cancer cells inhibited survival, vascular endothelial growth factor (VEGF) expression, angiogenesis, cancer cell migration and invasion, and HIF-1α protein expression and stability under hypoxia. These findings demonstrate that 15-LOX-1 expression loss in cancer cells promotes metastasis and that therapeutically targeting ubiquitous 15-LOX-1 loss in cancer cells has the potential to suppress metastasis.


Assuntos
Araquidonato 15-Lipoxigenase/biossíntese , Neoplasias do Colo/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Araquidonato 15-Lipoxigenase/genética , Hipóxia Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Metástase Neoplásica , Fator A de Crescimento do Endotélio Vascular
19.
BMC Genomics ; 15: 86, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24479613

RESUMO

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.


Assuntos
Abelhas/genética , Genes de Insetos , Animais , Composição de Bases , Bases de Dados Genéticas , Sequências Repetitivas Dispersas/genética , Anotação de Sequência Molecular , Fases de Leitura Aberta/genética , Peptídeos/análise , Análise de Sequência de RNA , Homologia de Sequência de Aminoácidos
20.
Sheng Wu Gong Cheng Xue Bao ; 29(6): 760-71, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24063236

RESUMO

Promoter is one of important elements for gene expression and regulation. In the construction of recombinants for metabolic engineering and synthetic biology, it is necessary to have the promoters with varying strengths for fine-tuning metabolic pathway to reach the metabolic balance, decrease the accumulation of intermediate and increase the production of target metabolite. However, the natural promoters available are not completely suitable for fine-tuning metabolic pathway due to discrete strength, lack of versatility and standardization. To deal with this problem, in this study, a new 88 bp synthetic promoter, which contains the typical -35 box, -10 box as well as ribosome bind site, was designed. Then, the promoter library was constructed by introducing some degenerate base pairs in the sequence of 6 bp in the upstream of the initial transcription site and 14 bp in spacer region between -35 and -10 box. 720 promoters with varying strengths were screened out from a library of more than 5 000 clones via the expression of red fluorescent protein mCherry under the control of the synthetic promoter. The sequence analysis based on 35 promoters with varying strengths showed the promoters with varying strengths are base preference. The purine bases in -13 site and pyrimidine bases in the transcriptional initiation sequence are of high frequency; the purine and pyrimidine bases are of the similar frequency in the spacer sequence between -35 and -10 box in strong promoter. In the end, five characterized promoters with varying strengths were selected to tune the synthetic pathway of cis,cis-muconic acid in Escherichia coli. The results showed that the promoters with varying strengths can regulate the production of cis,cis-muconic acid and the accumulation of the intermediate catechol.


Assuntos
Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Engenharia Metabólica/métodos , Regiões Promotoras Genéticas , Ácido Sórbico/análogos & derivados , Sequência de Bases , Escherichia coli/metabolismo , Genes Bacterianos , Dados de Sequência Molecular , Ácido Sórbico/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA