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1.
Food Chem ; 306: 125616, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622832

RESUMO

This research aimed to explore the role of protein S-nitrosylation in regulating the tenderness of postmortem beef, from the perspective of µ-calpain autolysis and protein proteolysis. Five bovine semimembranosus muscles were incubated with three treatments including S-nitrosoglutathione (GSNO, nitric oxide donor), normal saline and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, nitric oxide synthase inhibitor). The results showed that the level of protein S-nitrosylation was improved by GSNO treatment and reduced by L-NAME treatment (p < 0.05). Compared to the control, GSNO treatment had higher shear force while L-NAME treatment presented lower shear force at 7 d postmortem (p < 0.05). In addition, µ-calpain autolysis, myofibrillar protein and desmin degradation were reduced by GSNO treatment and accelerated by L-NAME treatment (p < 0.05). Therefore, it can be speculated that protein S-nitrosylation could affect beef tenderization by regulating the autolysis of µ-calpain and the degradation of myofibrillar proteins.

2.
Chemosphere ; 241: 125028, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629233

RESUMO

The kinetics of elemental mercury (Hg0) release from fly ashes and hydrated fly ash cement pastes was investigated using a homemade Hg measurement system. Three types of fly ash (FA) and ordinary Portland cement (OPC) were used to prepare cement pastes. After standard curing for 28 days, the hydrated cement paste (HCP) was ground into a fine powder for Hg emission measurements. Detectable Hg0 was found released from both fly ashes and hydrated fly ash cement pastes. The results show that elevated temperatures and evaporation of the capillary pore water in wet HCP samples accelerate Hg0 release. Both desorption of Hg0 from the particle surface of HCP powder and migration of Hg0 from the inner pores contribute to Hg0 release. The kinetic calculation indicates that the hydration products of hydrated fly ash cement have little immobilization effect on Hg0, which is mainly physically encapsulated in the HCP particles by hydration products.

3.
Stem Cell Res Ther ; 10(1): 281, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481100

RESUMO

Stem cell therapy has been applied in many fields. Basic and clinical studies on stem cell therapy for acute kidney injury (AKI) have been conducted. Stem cells have been found to exert renal protection through a variety of mechanisms, such as regulating the immune system and secreting growth factors, cytokines, and extracellular vesicles (EVs). Among them, EVs are considered to be important mediators for stem cell protection because they contain various biological components, including microRNAs (miRNAs). miRNAs are a class of small RNAs that function in posttranscriptional gene regulation. A number of studies have confirmed that miRNAs in stem cell-derived EVs can protect from AKI. miRNAs can enter the injured renal tissue through EVs released from stem cells, thereby exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenesis effects on AKI. However, the stem cell sources and AKI models used in these studies have differed. This article will summarize the miRNAs that play a role in kidney protection in stem cell EVs and clarifies the treatment characteristics and mechanisms of different miRNAs. This may provide a reference for clinical practice for acute and chronic kidney diseases.

4.
Clin Exp Ophthalmol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483932

RESUMO

PURPOSE: To explore the mechanisms of erythropoietin (EPO) in maintaining outer blood-retinal barrier (BRB) in diabetic rats. METHODS: Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin, and then followed by intravitreal injection of EPO. Two and four weeks later, the permeability of outer BRB was examined with FITC-dextran leakage assay, following a method to demarcate the inner and outer retina based on retinal blood supply. The glyoxal-treated ARPE-19 cells, incubated with EPO, soluble EPO receptor (sEPOR), Gö6976, or digoxin, were studied for cell viability and barrier function. The expressions of ZO-1, occludin, VEGFR2, HIF-1α, MAPKs, and AKT were examined with Western blot and immunofluorescence. RESULTS: The major Leakage of FITC-dextran was detected in the outer nuclear layer in both 2- and 4-week diabetic rats. The leakage was largely ameliorated in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in the RPE-Bruch's membrane choriocapillaris complex were significantly decreased, whereas HIF-1α and JNK pathways were activated, in 4-week diabetic rats. These changes were prevented by EPO treatment. The in vitro study with ARPE-19 cells confirmed these changes, and the protective effect of EPO was abolished by sEPOR. Gö6976 and digoxin rescued the tight junction and barrier function in glyoxal-treated ARPE-19 cells. CONCLUSIONS: In early diabetic rats, the outer BRB might be more severely damaged and its breakdown is the major factor for retinal oedema. EPO maintains the outer BRB integrity through down-regulation of HIF-1α and JNK signallings, and thus up-regulating ZO-1 and occludin expressions in RPE cells.

5.
Phys Chem Chem Phys ; 21(32): 17868-17879, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31380535

RESUMO

Exactly predicting the packing structures of a given molecule is a crucial topic in crystal engineering, while it remains still challenging, as it requires huge calculations, largely above common computation cost and time limitations. However, current progress in high throughput calculations makes the fast screening of structures and properties feasible. In the present work, we exemplify this by considering a special case of ascertainment of the molecular stacking mode and shear properties of energetic materials. Four energetic π-bonded molecules, 1,3,5-trinitrobenzene, 2,4,6-trinitroaniline, 1,3-diamino-2,4,6-trinitrobenzene and 2,4,6-triamino-1,3,5-trinitrobenzene, with a different number of H atoms replaced by amino groups, are adopted as samples to scan the potential energy surfaces (PESs) of dimers through high throughput calculations. It is found that the parallel stacking mode is the most energetically favored, followed by the T-shaped, coplanar and crossing ones. Such an energetically favored stacking mode is observed in all related π-stacked crystal structures at ambient conditions or low temperatures. It shows that the stacking mode can be ascertained through the PES scanning of dimers, and thereby, the stacking structures and properties related to the stacking mode, like mechanical anisotropism, can be quickly screened by means of high throughput calculations.

6.
Int J Med Sci ; 16(6): 800-812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337953

RESUMO

Cervical cancer is a common malignant tumour of the female reproductive system that seriously threatens the health of women. The aims of this study were to identify key genes and pathways and to illuminate new molecular mechanisms underlying cervical cancer. Altogether, 1829 DEGs were identified, including 794 significantly down-regulated DEGs and 1035 significantly up-regulated DEGs. GO analysis suggested that the up-regulated DEGs were mainly enriched in mitotic cell cycle processes, including DNA replication, organelle fission, chromosome segregation and cell cycle phase transition, and that the down-regulated DEGs were primarily enriched in development and differentiation processes, such as tissue development, epidermis development, skin development, keratinocyte differentiation, epidermal cell differentiation and epithelial cell differentiation. KEGG pathway analysis showed that the DEGs were significantly enriched in cell cycle, DNA replication, the p53 signalling pathway, pathways in cancer and oocyte meiosis. The top 9 hub genes with a high degree of connectivity (over 72 in the PPI network) were down-regulated TSPO, CCND1, and FOS and up-regulated CDK1, TOP2A, CCNB1, PCNA, BIRC5 and MAD2L1. Module analysis indicated that the top 3 modules were significantly enriched in mitotic cell cycle, DNA replication and regulation of cell cycle (P < 0.01). The heat map based on TCGA database preliminarily demonstrated the expression change of the key genes in cervical cancer. GSEA results were basically coincident with the front enrichment analysis results. By comprehensive analysis, we confirmed that cell cycle was a key biological process and a critical driver in cervical cancer. In conclusion, this study identified DEGs and screened the key genes and pathways closely related to cervical cancer by bioinformatics analysis, simultaneously deepening our understanding of the molecular mechanisms underlying the occurrence and progression of cervical cancer. These results might hold promise for finding potential therapeutic targets of cervical cancer.

7.
PLoS One ; 14(5): e0216116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063467

RESUMO

Mutations that confer herbicide resistance are a primary concern for herbicide-based chemical control of invasive plants and are often under-characterized structurally and functionally. As the outcome of selection pressure, resistance mutations usually result from repeated long-term applications of herbicides with the same mode of action and are discovered through extensive field trials. Here we used acetohydroxyacid synthase (AHAS) of Kochia scoparia (KsAHAS) as an example to demonstrate that, given the sequence of a target protein, the impact of genetic mutations on ligand binding could be evaluated and resistance mutations could be identified using a biophysics-based computational approach. Briefly, the 3D structures of wild-type (WT) and mutated KsAHAS-herbicide complexes were constructed by homology modeling, docking and molecular dynamics simulation. The resistance profile of two AHAS-inhibiting herbicides, tribenuron methyl and thifensulfuron methyl, was obtained by estimating their binding affinity with 29 KsAHAS (1 WT and 28 mutated) using 6 molecular mechanical (MM) and 18 hybrid quantum mechanical/molecular mechanical (QM/MM) methods in combination with three structure sampling strategies. By comparing predicted resistance with experimentally determined resistance in the 29 biotypes of K. scoparia field populations, we identified the best method (i.e., MM-PBSA with single structure) out of all tested methods for the herbicide-KsAHAS system, which exhibited the highest accuracy (up to 100%) in discerning mutations conferring resistance or susceptibility to the two AHAS inhibitors. Our results suggest that the in silico approach has the potential to be widely adopted for assessing mutation-endowed herbicide resistance on a case-by-case basis.

9.
Vet Microbiol ; 231: 40-44, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955821

RESUMO

Haemophilus parasuis is a common colonizer of the upper respiratory tract of swine and frequently causes disease, especially in weaner pigs. To date, limited epidemiological data was available for H. parasuis from healthy pigs, which might be carriers of potential pathogenic strains. In this study, from September 2016 to October 2017, we investigated the prevalence and characteristics of H. parasuis from healthy pigs in China. Totally, we obtained 244 isolates from 1675 nasal samples from 6 provinces. H. parasuis isolation was more successful in weaner pigs (22.6%, 192/849), followed by finisher pigs (9.3%, 43/463), and sows (2.5%, 9/363). The most prevalent serovars were 7 (20.1%, 49/244), followed by 3 (14.8%, 36/244), 2 (14.3%, 35/244), 11 (12.7%, 31/244), 5/12 (5.7%, 14/244) and 4 (2.5%, 6/244). Bimodal or multimodal distributions of MICs were observed for most of the tested drugs, which suggested the presence of non-wild type populations. It was noted that the MIC90 values of tilmicosin (64 µg/ml) was relatively higher than that reported in previous studies. Our results suggest that: 1) potentially pathogenic serovars of H. parasuis are identified in healthy pigs, and 2) elevated MICs and presence of mechanisms of resistance not yet described for clinically important antimicrobial agents would increase the burden of disease caused by H. parasuis.


Assuntos
Antibacterianos/farmacologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/efeitos dos fármacos , Doenças dos Suínos/epidemiologia , Suínos/microbiologia , Matadouros , Animais , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Portador Sadio/veterinária , China/epidemiologia , Fazendas , Infecções por Haemophilus/epidemiologia , Haemophilus parasuis/isolamento & purificação , Testes de Sensibilidade Microbiana , Nariz/microbiologia , Reação em Cadeia da Polimerase , Prevalência , Sorogrupo , Doenças dos Suínos/microbiologia , Desmame
10.
BMC Bioinformatics ; 20(Suppl 2): 101, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871461

RESUMO

BACKGROUND: Reference genome selection is a prerequisite for successful analysis of next generation sequencing (NGS) data. Current practice employs one of the two most recent human reference genome versions: HG19 or HG38. To date, the impact of genome version on SNV identification has not been rigorously assessed. METHODS: We conducted analysis comparing the SNVs identified based on HG19 vs HG38, leveraging whole genome sequencing (WGS) data from the genome-in-a-bottle (GIAB) project. First, SNVs were called using 26 different bioinformatics pipelines with either HG19 or HG38. Next, two tools were used to convert the called SNVs between HG19 and HG38. Lastly we calculated conversion rates, analyzed discordant rates between SNVs called with HG19 or HG38, and characterized the discordant SNVs. RESULTS: The conversion rates from HG38 to HG19 (average 95%) were lower than the conversion rates from HG19 to HG38 (average 99%). The conversion rates varied slightly among the various calling pipelines. Around 1.5% SNVs were discordantly converted between HG19 or HG38. The conversions from HG38 to HG19 had more SNVs which failed conversion and more discordant SNVs than the opposite conversion (HG19 to HG38). Most of the discordant SNVs had low read depth, were low confidence SNVs as defined by GIAB, and/or were predominated by G/C alleles (52% observed versus 42% expected). CONCLUSION: A significant number of SNVs could not be converted between HG19 and HG38. Based on careful review of our comparisons, we recommend HG38 (the newer version) for NGS SNV analysis. To summarize, our findings suggest caution when translating identified SNVs between different versions of the human reference genome.


Assuntos
Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
11.
Plant Sci ; 280: 321-329, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30824011

RESUMO

Cysteine functions not only as an amino acid in proteins but also as a precursor for a large number of essential biomolecules. Cysteine is synthesized via the incorporation of sulfide to O-acetylserine under the catalysis of O-acetylserine(thiol)lyase (OASTL). In dicotyledonous Arabidopsis, nine OASTL genes have been reported. However, in their null mutants, only the mutant of CS26 encoding S-sulfocysteine synthase showed the visible phenotypic changes, displaying significantly small plants and pale-green leaves under long-day condition but not short-day condition. Up to now, no OASTL gene or mutant has been identified in monocotyledon. In this study, we isolated a green-revertible albino mutant gra78 in rice (Oryza sativa). Its albino phenotype at the early seedling stage was sensitive to temperature but independent of photoperiod. Map-based cloning revealed that candidate gene LOC_Os01g59920 of GRA78 encodes a putative S-sulfocysteine synthase showing significant similarity with Arabidopsis CS26. Complementation experiment confirmed that mutation in LOC_Os01g59920 accounted for the mutant phenotype of gra78. GRA78 is constitutively expressed in all tissues and its encoded protein is targeted to the chloroplast. In addition, qRT-PCR suggested that expression levels of four OASTL homolog genes and five photosynthetic genes were remarkably down-regulated.


Assuntos
Liases/metabolismo , Oryza/enzimologia , Cloroplastos/fisiologia , Cloroplastos/ultraestrutura , Liases/genética , Liases/ultraestrutura , Mutação , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/ultraestrutura , Fenótipo , Fotossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plântula/enzimologia , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/ultraestrutura
12.
BMC Bioinformatics ; 20(Suppl 2): 100, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871477

RESUMO

BACKGROUND: The ability to predict which pairs of amino acid residues in a protein are in contact with each other offers many advantages for various areas of research that focus on proteins. For example, contact prediction can be used to reduce the computational complexity of predicting the structure of proteins and even to help identify functionally important regions of proteins. These predictions are becoming especially important given the relatively low number of experimentally determined protein structures compared to the amount of available protein sequence data. RESULTS: Here we have developed and benchmarked a set of machine learning methods for performing residue-residue contact prediction, including random forests, direct-coupling analysis, support vector machines, and deep networks (stacked denoising autoencoders). These methods are able to predict contacting residue pairs given only the amino acid sequence of a protein. According to our own evaluations performed at a resolution of +/- two residues, the predictors we trained with the random forest algorithm were our top performing methods with average top 10 prediction accuracy scores of 85.13% (short range), 74.49% (medium range), and 54.49% (long range). Our ensemble models (stacked denoising autoencoders combined with support vector machines) were our best performing deep network predictors and achieved top 10 prediction accuracy scores of 75.51% (short range), 60.26% (medium range), and 43.85% (long range) using the same evaluation. These tests were blindly performed on targets from the CASP11 dataset; and the results suggested that our models achieved comparable performance to contact predictors developed by groups that participated in CASP11. CONCLUSIONS: Due to the challenging nature of contact prediction, it is beneficial to develop and benchmark a variety of different prediction methods. Our work has produced useful tools with a simple interface that can provide contact predictions to users without requiring a lengthy installation process. In addition to this, we have released our C++ implementation of the direct-coupling analysis method as a standalone software package. Both this tool and our RFcon web server are freely available to the public at http://dna.cs.miami.edu/RFcon /.


Assuntos
Biologia Computacional/métodos , Aprendizado de Máquina/normas , Proteínas/metabolismo , Sequência de Aminoácidos
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(3): 207-211, 2019 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-30835347

RESUMO

OBJECTIVE: To carry out genetic testing for a family affected with distal hereditary motor neuronopathy V (dHMN V). METHODS: Potential mutations of the GARS and BSCL2 genes were analyzed with PCR and Sanger sequencing. Suspected mutation was verified among unaffected members of the family and 100 healthy controls. Prenatal diagnosis was provided based on the above results. RESULTS: Sequencing analysis has identified a heterozygous c.269C>T (p.S90L) mutation in the BSCL2 gene, which resulted in replacement of Serine (TCG) to Leucine (TTG). The same mutation was found in all other 3 patients from the pedigree but not among unaffected members or the 100 healthy controls. By prenatal diagnosis, the fetus did not carry the above mutation. CONCLUSION: Pathogenic mutation of BSCL2 gene probably underlies the dHMN V in this pedigree, which enabled prenatal diagnosis for the proband.


Assuntos
Atrofia Muscular Espinal , Feminino , Subunidades gama da Proteína de Ligação ao GTP , Humanos , Mutação , Linhagem , Gravidez
14.
PLoS One ; 14(3): e0213430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30849106

RESUMO

INTRODUCTION: Using machine learning techniques, we developed a brief questionnaire to aid neurologists and neuropsychologists in the screening of mild cognitive impairment (MCI) and dementia. METHODS: With the reduction of the survey size as a goal of this research, feature selection based on information gain was performed to rank the contribution of the 45 items corresponding to patient responses to the specified questions. The most important items were used to build the optimal screening model based on the accuracy, practicality, and interpretability. The diagnostic accuracy for discriminating normal cognition (NC), MCI, very mild dementia (VMD) and dementia was validated in the test group. RESULTS: The screening model (NMD-12) was constructed with the 12 items that were ranked the highest in feature selection. The receiver-operator characteristic (ROC) analysis showed that the area under the curve (AUC) in the test group was 0.94 for discriminating NC vs. MCI, 0.88 for MCI vs. VMD, 0.97 for MCI vs. dementia, and 0.96 for VMD vs. dementia, respectively. DISCUSSION: The NMD-12 model has been developed and validated in this study. It provides healthcare professionals with a simple and practical screening tool which accurately differentiates NC, MCI, VMD, and dementia.

15.
Chem Commun (Camb) ; 55(18): 2628-2631, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30742165

RESUMO

A thorough theoretical exploration of the formation mechanism of arylpentazole (cyclo-N5), the key precursor of cyclo-N5-, has been performed. Three arylpentazene conformers were found as intermediates, and one is crucial for cyclo-N5 production. By scrutinizing the complete reaction pathways and substituent effects, we propose a potential solution to the enhancement of cyclo-N5 yield.

16.
Phys Chem Chem Phys ; 21(5): 2397-2409, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30649112

RESUMO

The intramolecular H transfer of energetic NO2-compounds has been recognized as a possible primary step in triggering molecular decomposition for a long time. Nevertheless, studies on H transfer in different complex situations are limited, lacking a comprehensive understanding of its role in NO2-compounds. In this work, twenty intramolecular H transfer reactions are studied for eighteen nitro compounds and compared with the NO2 partition in thermodynamics and kinetics. Three factors, including the high planarity of molecules, the short transfer distance between the target H and O atoms and the high protonation of the H atom are identified to facilitate H transfer. If H transfer is more kinetically favorable than NO2 partition, and if a reverse H transfer occurs with a barrier less than 30 kcal mol-1, we define it as a reversible one. In our study, for those impact insensitive nitro compounds with H50 larger than that of 2,4,6-trinitrotoluene, all of them are found to be accompanied with reversible H transfer, while the impact sensitive compounds are not. Accordingly, we propose that the reversible H transfer can effectively buffer the external stimuli against the molecular decomposition through chemical energy absorption/release. Beyond the conventional understanding that H transfer triggers molecular decomposition, this work builds a new correlation between reversible H transfer and the low impact sensitivity of energetic nitro-compounds.

17.
Food Chem ; 274: 407-414, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30372958

RESUMO

This study aimed to determine the characteristics, metabolic pathways and cellular functions of S-nitrosylated proteins from pork postmortem muscle using bioinformatics analysis. The results showed that S-nitrosylated proteins had a broad range of molecular weight and pI value and were mainly located in the functional region of secondary structure. The motif revealed the lysine (K) positioned at -5, -7, +1 and +5 through the S-nitrosocysteine while "C-X-X-C" was identified as the motif for non-S-nitrosylation-modified cysteine. The proteins were widely localized in cell compartments and mostly belonged to enzymes participating in the metabolic process. Glycolysis was the most significant pathways of S-nitrosylated proteins in postmortem muscle. The cell death of muscle cells was predicted to be inhibited by S-nitrosylation with the potential influence on the apoptosis. Those identified pathways and cellular functions of S-nitrosylation are proposed to have a profound influence on meat quality and should be highly regarded.


Assuntos
Biologia Computacional , Células Musculares/citologia , Células Musculares/metabolismo , Proteínas Musculares/metabolismo , Óxido Nítrico/metabolismo , Animais , Autopsia , Morte Celular , Suínos
18.
BMC Syst Biol ; 12(Suppl 7): 115, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30547796

RESUMO

BACKGROUND: Reconstruction of gene regulatory networks (GRNs), also known as reverse engineering of GRNs, aims to infer the potential regulation relationships between genes. With the development of biotechnology, such as gene chip microarray and RNA-sequencing, the high-throughput data generated provide us with more opportunities to infer the gene-gene interaction relationships using gene expression data and hence understand the underlying mechanism of biological processes. Gene regulatory networks are known to exhibit a multiplicity of interaction mechanisms which include functional and non-functional, and linear and non-linear relationships. Meanwhile, the regulatory interactions between genes and gene products are not spontaneous since various processes involved in producing fully functional and measurable concentrations of transcriptional factors/proteins lead to a delay in gene regulation. Many different approaches for reconstructing GRNs have been proposed, but the existing GRN inference approaches such as probabilistic Boolean networks and dynamic Bayesian networks have various limitations and relatively low accuracy. Inferring GRNs from time series microarray data or RNA-sequencing data remains a very challenging inverse problem due to its nonlinearity, high dimensionality, sparse and noisy data, and significant computational cost, which motivates us to develop more effective inference methods. RESULTS: We developed a novel algorithm, MICRAT (Maximal Information coefficient with Conditional Relative Average entropy and Time-series mutual information), for inferring GRNs from time series gene expression data. Maximal information coefficient (MIC) is an effective measure of dependence for two-variable relationships. It captures a wide range of associations, both functional and non-functional, and thus has good performance on measuring the dependence between two genes. Our approach mainly includes two procedures. Firstly, it employs maximal information coefficient for constructing an undirected graph to represent the underlying relationships between genes. Secondly, it directs the edges in the undirected graph for inferring regulators and their targets. In this procedure, the conditional relative average entropies of each pair of nodes (or genes) are employed to indicate the directions of edges. Since the time delay might exist in the expression of regulators and target genes, time series mutual information is combined to cooperatively direct the edges for inferring the potential regulators and their targets. We evaluated the performance of MICRAT by applying it to synthetic datasets as well as real gene expression data and compare with other GRN inference methods. We inferred five 10-gene and five 100-gene networks from the DREAM4 challenge that were generated using the gene expression simulator GeneNetWeaver (GNW). MICRAT was also used to reconstruct GRNs on real gene expression data including part of the DNA-damaged response pathway (SOS DNA repair network) and experimental dataset in E. Coli. The results showed that MICRAT significantly improved the inference accuracy, compared to other inference methods, such as TDBN, etc. CONCLUSION: In this work, a novel algorithm, MICRAT, for inferring GRNs from time series gene expression data was proposed by taking into account dependence and time delay of expressions of a regulator and its target genes. This approach employed maximal information coefficients for reconstructing an undirected graph to represent the underlying relationships between genes. The edges were directed by combining conditional relative average entropy with time course mutual information of pairs of genes. The proposed algorithm was evaluated on the benchmark GRNs provided by the DREAM4 challenge and part of the real SOS DNA repair network in E. Coli. The experimental study showed that our approach was comparable to other methods on 10-gene datasets and outperformed other methods on 100-gene datasets in GRN inference from time series datasets.


Assuntos
Algoritmos , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Entropia , Fatores de Tempo
19.
Artigo em Inglês | MEDLINE | ID: mdl-30381750

RESUMO

Objective: Recent studies have demonstrated that LIN28B/let-7 plays a role in the regulation of pubertal onset in mammals. However, the role of LIN28B/ let-7 in the onset of ovine puberty remains unknown. We cloned the Duolang sheep Lin28B cDNA sequence, detected the expression change of LIN28B, let-7a and let-7g in hypothalamus, pituitary and ovary tissues at three different pubertal stages. Methods: The reverse transcriptase polymerase chain reaction (RT-PCR) was used to clone the cDNA sequence of LIN28B gene from Duolang sheep and the bioinformatics methods were applied to analyze the amino acid sequence of LIN28B protein. The mRNA expression levels of the LIN28B gene at different pubertal stages were examined by real time RT-PCR. Results: LIN28B cDNA of Duolang sheep was cloned, and two transcripts were obtained. The amino acid sequence of transcript 1 shares 99.60%, 98.78% and 94.80% identity with those of goat, wild yak and pig, respectively. Strong LIN28B mRNA expression was detected in the hypothalamus, pituitary, ovary, oviduct and uterus, while moderate expression was found in the liver, kidney, spleen and heart, weak expression was observed in the heart. No expression was found in the lungs. QPCR and western-blot analysis revealed that the LIN28B was highly expressed in the hypothalamus and ovary at prepuberty stages, and this expression significantly decreased from the prepuberty to puberty stages (P<0.05). Markedly increased levels of mRNA expression were detected in the pituitary from prepuberty to puberty (P < 0.05) and then significantly decreased from puberty to postpuberty (P < 0.05). The expression levels of let-7a and let-7g showed no significant changes among different pubertal stages (P > 0.05). Conclusion: These results provided a foundation for determining the functions of LIN28B/let-7 and their role in the onset of sheep puberty.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(8): 678-683, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30384864

RESUMO

Objective To evaluate the therapeutic effect and possible mechanism of IL-12 monoclonal antibody (IL-12 mAb) on IL-10 knockout(IL-10-/-) mice and its possible mechanism. Methods Sixteen male IL-10-/- mice of 15 weeks old were randomly divided into control group and IL-12 mAb treatment group. The IL-12 mAb treatment group were given intraperitoneal injection of IL-12 mAb (25 mg/kg, once per week), and the control group was given intraperitoneal injection of 0.2 mL of normal saline. After 4 weeks of intervention, the inflammatory bowel disease activity index (DAI) and HE staining were used to evaluate the intestinal inflammation symptoms and histological changes. The intestinal mucosal permeability test was used to evaluate the intestinal mucosal barrier function of the two groups. The expression of claudin-1 in intestinal mucosa was detected by Western blot analysis. The Th1/Th2 cell balance of intestinal mucosa was evaluated by flow cytometry. The ELISA was used to evaluate IL-13 and tumor necrosis factor alpha(TNF-α) of intestinal mucosal of the two groups. The expression of phosphorylated signal transducer and activator of transcription (p-STAT6) in intestinal mucosa was detected by Western blot nanlysis. Results Three and 4 weeks after IL-12 mAb treatment, the DAI and intestinal inflammation scores of IL-12 mAb treatment group were significantly lower than the control group. At the same time, the intestinal mucosal permeability of IL-12 mAb treatment group was significantly lower than that of the control group, and the expression of claudin-1 in intestinal mucosa was significantly higher than that of the control group. At the same time, IL-12 mAb treatment inhibited the proportion of Th1 cells in the intestinal mucosa and up-regulated the proportion of Th2 cells. In the signal pathway analysis, IL-12 mAb treatment increased the levels of p-STAT6 and IL-13 in the intestinal mucosa and inhibited the level of TNF-α. Conclusion IL-12 mAb effectively alleviates intestinal inflammation in the Crohn's disease animal model and protect the intestinal mucosal barrier, which may be through inhibition of Th1 cell immune response in the intestinal mucosa and up-regulation of STAT6 signaling.

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