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1.
Nat Med ; 30(2): 507-518, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38233586

ABSTRACT

The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel (P = 0.0002 for B cell GES; P = 0.0165 for CD19 expression) but not SOC (P = 0.9374 for B cell GES; P = 0.5526 for CD19 expression). Axi-cel showed superior event-free survival over SOC irrespective of B cell GES and CD19 expression (P = 8.56 × 10-9 for B cell GES high; P = 0.0019 for B cell GES low; P = 3.85 × 10-9 for CD19 gene high; P = 0.0017 for CD19 gene low). Low CD19 expression in malignant cells correlated with a tumor GES consisting of immune-suppressive stromal and myeloid genes, highlighting the inter-relation between malignant cell features and immune contexture substantially impacting axi-cel outcomes. Tumor burden, lactate dehydrogenase and cell-of-origin impacted SOC more than axi-cel outcomes. T cell activation and B cell GES, which are associated with improved axi-cel outcome, decreased with increasing lines of therapy. These data highlight differences in resistance mechanisms to axi-cel and SOC and support earlier intervention with axi-cel.


Subject(s)
Biological Products , Lymphoma, Large B-Cell, Diffuse , Humans , Immunotherapy, Adoptive , Tumor Microenvironment , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/therapy , B-Lymphocytes , Adaptor Proteins, Signal Transducing , Antigens, CD19
2.
Int J Biol Macromol ; 236: 123883, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36889614

ABSTRACT

Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii), a valuable herbal medicine in China, has great medicinal and edible value. Polysaccharides, as one of the main active components of A. roxburghii, comprise glucose, arabinose, xylose, galactose, rhamnose, and mannose in different molar ratios and glycosidic bond types. By varying the sources and extraction methods of A. roxburghii polysaccharides (ARPS), different structural characteristics and pharmacological activities can be elucidated. ARPS has been reported to exhibit antidiabetic, hepatoprotective, anti-inflammatory, antioxidant, antitumor, and immune regulation activities. This review summarizes the available literature on the extraction and purification methods, structural features, biological activities, and applications of ARPS. The shortcomings of the current research and potential focus in future studies are also highlighted. This review provides systematic and current information on ARPS to promote their further exploitation and application.


Subject(s)
Drugs, Chinese Herbal , Orchidaceae , Polysaccharides/pharmacology , Polysaccharides/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Glucose , Drugs, Chinese Herbal/chemistry , Galactose/chemistry , Orchidaceae/chemistry
3.
Plant Sci ; 327: 111566, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36513314

ABSTRACT

Anoectochilus roxburghii is a rare and precious plant with medicinal and healthcare functions. Embryo abortion caused the lack of resources. Polyamine promoted its flowering and stress resistance in our previous study. But the mechanism remains unclear. The WRKY transcription factor family has been linked to a variety of biological processes in plants. In this study, two WRKY TFs (ArWRKY5 and ArWRKY20) of A. roxburghii, which showed significant response to Spd treatment, were identified and functionally analyzed. Tissue specific expression analyzation showed both of them mostly present in the flower. And ArWRKY5 expressed highest in the flower bud stage (-1 Flowering), while ArWRKY20 showed the highest expression in earlier flower bud stage (-2 Flowering) and the expression gradually decreased with flowering. The transcriptional activation activity assay and subcellular localization revealed that ArWRKY5 and ArWRKY20 were located in the nucleus and ArWRKY20 showed transcriptional activity. The heterologous expression of ArWRKY5 in Arabidopsis thaliana showed earlier flowering, while overexpression of ArWRKY20 delayed flowering. But the OE-ArWRKY20 lines had a robust body shape and a very significant increase in the number of rosette leaves. Furthermore, stamens and seed development were positively regulated by these two ArWRKYs. These results indicated that ArWRKY5 and ArWRKY20 not only play opposite roles in the floral development, but also regulate the plant growth and seed development in A. thaliana. But their specific biological functions and mechanism in A. roxburghii need to be investigated further.


Subject(s)
Orchidaceae , Plant Proteins , Arabidopsis/genetics , Arabidopsis/metabolism , Flowers , Gene Expression Regulation, Plant , Plant Leaves/metabolism , Plant Proteins/metabolism , Transcription Factors/metabolism , Orchidaceae/genetics , Orchidaceae/metabolism
4.
Int J Mol Sci ; 25(1)2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38203324

ABSTRACT

Gibberellin (GA) is an important plant hormone that is involved in various physiological processes during plant development. Sweet cherries planted in southern China have always encountered difficulty in bearing fruit. In recent years, gibberellin has successfully solved this problem, but there has also been an increase in malformed fruits. This study mainly explores the mechanism of malformed fruit formation in sweet cherries. By analyzing the synthesis pathway of gibberellin using metabolomics and transcriptomics, the relationship between gibberellin and the formation mechanism of deformed fruit was preliminarily determined. The results showed that the content of GA3 in malformed fruits was significantly higher than in normal fruits. The differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were mainly enriched in pathways such as "plant hormone signal transduction", "diterpenoid biosynthesis", and "carotenoid biosynthesis". Using Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) analysis, the gibberellin hydrolase gene GA2ox and gibberellin synthase genes GA20ox and GA3ox were found to be significantly up-regulated. Therefore, we speculate that the formation of malformed fruits in sweet cherries may be related to the accumulation of GA3. This lays the foundation for further research on the mechanism of malformed sweet cherry fruits.


Subject(s)
Prunus avium , Prunus avium/genetics , Transcriptome , Fruit/genetics , Plant Growth Regulators , Gibberellins , Metabolome , China
5.
Food Chem ; 384: 132381, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35196592

ABSTRACT

Cuticular wax has been implicated in the first line of plant defense mechanism against external stresses. In this study, cuticular wax on the fruits of two rabbiteye blueberry cultivars cv. Baldwin and Brightwell were examined in terms of the morphology and chemical composition during fruit development in the presence and absence of pre-harvest melatonin (MT) treatment. It revealed that the crystal wax appeared as numerous tubules, and its morphology was not affected by MT treatment. A dominant constituent of triterpenoid at veraison stage was ß-amyrin (45.62% of total wax) in Baldwin and oleanolic acid (22.79% of total wax) in Brightwell. Exogenous MT application significantly promoted fruit quality and increased total content of cuticular wax, however, the effect of MT on individual wax components greatly varied depending on cultivars and fruit developmental stage. Consequently, MT application may enhance sustainability of post-harvest fruit production systems by facilitating accumulation of cuticular wax.


Subject(s)
Blueberry Plants , Melatonin , Vaccinium , Blueberry Plants/chemistry , Fruit/chemistry , Melatonin/analysis , Waxes/chemistry
6.
Rheumatol Ther ; 7(1): 173-190, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31912462

ABSTRACT

INTRODUCTION: The Janus kinase (JAK) inhibitor therapeutic class has shown significant clinical benefit in the treatment of rheumatoid arthritis (RA). We sought to gain insight into the mode of action and immunological effects of filgotinib, a JAK1 selective inhibitor, in active RA by analyzing secreted and cell-based biomarkers key to RA pathophysiology in two phase 2b trials of filgotinib in active RA. METHODS: Immune cell subsets and 34 serum biomarkers were analyzed longitudinally over 12 weeks using blood samples collected from patients with active RA receiving filgotinib (100 or 200 mg once daily) or placebo (PBO) in the two phase 2b trials (DARWIN 1, on a background of methotrexate, and DARWIN 2, as monotherapy). RESULTS: Consistently across both studies, filgotinib treatment decreased multiple immune response biomarkers that have key roles in RA for immune response, and decreased markers that promote matrix degradation, angiogenesis, leukocyte adhesion, and recruitment. Filgotinib did not significantly modulate T and natural killer (NK) lymphoid subsets, but slightly increased B cell numbers after 12 weeks. Multiple correlations were observed for changes in biomarkers with disease activity score 28-CRP. MIP1ß showed modest predictivity at baseline for ACR50 response at 12 weeks in the 100 mg filgotinib dose across both studies (AUROC, 0.65 and 0.67, p < 0.05). CONCLUSIONS: Filgotinib regulates biomarkers from multiple pathways, indicative of direct and indirect network effects on the immune system and the stromal response. These effects were not associated with reductions of major circulating lymphoid populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01888874, NCT01894516.

7.
Nat Neurosci ; 20(8): 1150-1161, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28671696

ABSTRACT

The postsynaptic density (PSD) contains a collection of scaffold proteins used for assembling synaptic signaling complexes. However, it is not known how the core-scaffold machinery associates in protein-interaction networks or how proteins encoded by genes involved in complex brain disorders are distributed through spatiotemporal protein complexes. Here using immunopurification, proteomics and bioinformatics, we isolated 2,876 proteins across 41 in vivo interactomes and determined their protein domain composition, correlation to gene expression levels and developmental integration to the PSD. We defined clusters for enrichment of schizophrenia, autism spectrum disorders, developmental delay and intellectual disability risk factors at embryonic day 14 and adult PSD in mice. Mutations in highly connected nodes alter protein-protein interactions modulating macromolecular complexes enriched in disease risk candidates. These results were integrated into a software platform, Synaptic Protein/Pathways Resource (SyPPRes), enabling the prioritization of disease risk factors and their placement within synaptic protein interaction networks.


Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/genetics , Post-Synaptic Density/genetics , Synapses/metabolism , Animals , Brain Diseases/genetics , Brain Diseases/metabolism , Disease Models, Animal , Guanylate Kinases/genetics , Membrane Proteins/genetics , Mice, Transgenic , Schizophrenia/genetics , Schizophrenia/metabolism , Signal Transduction/genetics , Synapses/genetics
8.
Int J Mol Sci ; 17(12)2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27983700

ABSTRACT

Starch is one of the most important storage carbohydrates in plants. Kiwifruit typically accumulate large amounts of starch during development. The fruit retain starch until commercial maturity, and its postharvest degradation is essential for consumer acceptance. The activity of genes related to starch degradation has, however, rarely been investigated. Based on the kiwifruit genome sequence and previously reported starch degradation-related genes, 17 novel genes were isolated and the relationship between their expression and starch degradation was examined using two sets of materials: ethylene-treated (100 µL/L, 20 °C; ETH) vs. control (20 °C; CK) and controlled atmosphere stored (CA, 5% CO2 + 2% O2, 0 °C) vs. normal atmosphere in cold storage (NA, 0 °C). Physiological analysis indicated that ETH accelerated starch degradation and increased soluble solids content (SSC) and soluble sugars (glucose, fructose and sucrose), while CA inhibited starch reduction compared with NA. Using these materials, expression patterns of 24 genes that may contribute to starch degradation (seven previously reported and 17 newly isolated) were analyzed. Among the 24 genes, AdAMY1, AdAGL3 and AdBAM3.1/3L/9 were significantly induced by ETH and positively correlated with starch degradation. Furthermore, these five genes were also inhibited by CA, conforming the likely involvement of these genes in starch degradation. Thus, the present study has identified the genes with potential for involvement in starch degradation in postharvest kiwifruit, which will be useful for understanding the regulation of kiwifruit starch content and metabolism.


Subject(s)
Actinidia/growth & development , Actinidia/genetics , Fruit/growth & development , Fruit/genetics , Genes, Plant , Starch/genetics , Starch/metabolism , Actinidia/drug effects , Environment, Controlled , Ethylenes/pharmacology , Fruit/drug effects , Gene Expression Regulation, Plant/drug effects , Phylogeny , Preservation, Biological , Temperature
9.
J Ultrasound Med ; 35(5): 905-15, 2016 May.
Article in English | MEDLINE | ID: mdl-27022172

ABSTRACT

OBJECTIVES: The aim of this systematic review was to compare the postnatal outcomes, genetic testing results, and sonographic findings in 3 subtypes of tetralogy of Fallot. METHODS: Thirty-six articles from the MEDLINE and EMBASE databases were selected for this review. The postnatal outcomes, karyotyping results, and sonographic findings of fetal tetralogy of Fallot with pulmonary stenosis, tetralogy of Fallot with pulmonary atresia, and tetralogy of Fallot with an absent pulmonary valve were collected and compared. RESULTS: The survival rates (termination of pregnancy was considered fetal death) for prenatally diagnosed tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve at the end of neonatal period were significantly lower than the rate for tetralogy of Fallot with pulmonary stenosis (P < .05). The survival rate for tetralogy of Fallot with pulmonary atresia was also lower at birth (P < .001). Major chromosomal anomalies were more frequently detected in tetralogy of Fallot with pulmonary stenosis (P< .05); conversely, 22q11 deletion was present more often in fetuses with tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve (P < .001). Compared to tetralogy of Fallot with pulmonary stenosis, a right aortic arch was more associated with tetralogy of Fallot with pulmonary atresia (32.6%; P < .05), and the ductus arteriosus was almost always absent in tetralogy of Fallot with an absent pulmonary valve (87.5%; P < .001). CONCLUSIONS: The postnatal outcomes, genetic testing results, and sonographic findings are different among subtypes of tetralogy of Fallot. Documenting those details at diagnosis can help specialists better counsel their patients.


Subject(s)
Genetic Testing/statistics & numerical data , Pregnancy Outcome/epidemiology , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/epidemiology , Ultrasonography, Prenatal/methods , Female , Humans , Pregnancy , Survival Analysis
10.
BMC Syst Biol ; 10 Suppl 1: 4, 2016 Jan 11.
Article in English | MEDLINE | ID: mdl-26818594

ABSTRACT

BACKGROUND: Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. METHODS: Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. RESULTS: We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. CONCLUSIONS: The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease mechanisms.


Subject(s)
Crohn Disease/genetics , Diabetes Mellitus, Type 2/genetics , Protein Domains , Area Under Curve , Bayes Theorem , Disease/genetics , Genetic Association Studies , Likelihood Functions , Phenotype
11.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1061-5, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-26226745

ABSTRACT

The viability and life span of pollen were evaluated by TTC (2,3,5-triphenyl tetrazlium chloride) and the peroxidase solution, the stigma receptivity were estimated by benzidine-H2O2 method and the fruiting characteristics were investigated. The results showed that (1) Anoectochilus roxburghii and A. formosanus appeared the same up-and-down trend of the pollen viability, increased and then decreased. The storage temperature and storage time had significant impact on the pollen viability. With the extension of storage time, the pollen activity decreased. 4 degrees C refrigerator storage may be extended the pollen vitality. (2) The stigma had receptivity in 1st day and reached the highest level in the 4th day after blooming. A. roxburghii lost receptivity in the 8th day while A. formosanus lost receptivity in the 10th day after blooming. (3) The different pollination had significant impact on seed setting rate. The seed setting rate of artificial cross-pollination was higher than that of the artificial self-pollination. Collecting pollen in the 3rd day and carrying out artificial cross-pollination in the 4th day after blooming can significantly improve seed setting rate. The results provided technical assurance for A. roxburghii and A. formosanus breeding of new varieties and seed breeding.


Subject(s)
Flowers/physiology , Fruit/growth & development , Orchidaceae/physiology , Pollen/growth & development , Cell Survival , China , Orchidaceae/growth & development , Reproduction , Temperature
12.
Planta ; 242(5): 1167-74, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26105653

ABSTRACT

MAIN CONCLUSION: Chinese medicinal herbs have a similar appearance and are easily confused, complicating identification via traditional methods. This study provided a scientific approach, based on DNA barcoding, to accurately and rapidly identify Anoectochilus roxburghii and its adulterants. This technology complements traditional methods of identification of medicinal herbs. A comparison of the DNA barcodes matK, psbA-trnH and ITS2 was performed to verify that the ITS2 sequence is an effective marker for rapidly and accurately identifying A. roxburghii and its closely related species. Genomic DNA extracted from A. roxburghii and its adulterants were used as templates and the ITS2 sequence was amplified using PCR amplification and sequencing. Species identification was conducted using BLAST1 and neighbor-joining trees. The 12 samples were successfully classified into four species based on the ITS2 sequence. The ITS2 sequence length of A. roxburghii was 253 bp. The average intra-specific genetic distance of A. roxburghii was 0.0021, markedly lower than the inter-specific genetic distance between A. roxburghii and its adulterants (0.0380). Our findings illustrate that ITS2 sequence can accurately and efficiently distinguish A. roxburghii and its adulterants. In addition, the results provided reference for molecular identification of other Chinese herbal medicine.


Subject(s)
DNA, Plant/genetics , DNA, Ribosomal Spacer/genetics , Orchidaceae/genetics , DNA Barcoding, Taxonomic , Sequence Analysis, DNA
13.
BMC Plant Biol ; 12: 190, 2012 Oct 11.
Article in English | MEDLINE | ID: mdl-23057995

ABSTRACT

BACKGROUND: The phytohormone ethylene is involved in a wide range of developmental processes and in mediating plant responses to biotic and abiotic stresses. Ethylene signalling acts via a linear transduction pathway leading to the activation of Ethylene Response Factor genes (ERF) which represent one of the largest gene families of plant transcription factors. How an apparently simple signalling pathway can account for the complex and widely diverse plant responses to ethylene remains yet an unanswered question. Building on the recent release of the complete tomato genome sequence, the present study aims at gaining better insight on distinctive features among ERF proteins. RESULTS: A set of 28 cDNA clones encoding ERFs in the tomato (Solanum lycopersicon) were isolated and shown to fall into nine distinct subclasses characterised by specific conserved motifs most of which with unknown function. In addition of being able to regulate the transcriptional activity of GCC-box containing promoters, tomato ERFs are also shown to be active on promoters lacking this canonical ethylene-responsive-element. Moreover, the data reveal that ERF affinity to the GCC-box depends on the nucleotide environment surrounding this cis-acting element. Site-directed mutagenesis revealed that the nature of the flanking nucleotides can either enhance or reduce the binding affinity, thus conferring the binding specificity of various ERFs to target promoters.Based on their expression pattern, ERF genes can be clustered in two main clades given their preferential expression in reproductive or vegetative tissues. The regulation of several tomato ERF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signalling pathways of the two hormones. CONCLUSIONS: The data reveal that regions flanking the core GCC-box sequence are part of the discrimination mechanism by which ERFs selectively bind to their target promoters. ERF tissue-specific expression combined to their responsiveness to both ethylene and auxin bring some insight on the complexity and fine regulation mechanisms involving these transcriptional mediators. All together the data support the hypothesis that ERFs are the main component enabling ethylene to regulate a wide range of physiological processes in a highly specific and coordinated manner.


Subject(s)
Ethylenes/metabolism , Plant Growth Regulators/metabolism , Plant Proteins/metabolism , Solanum lycopersicum/genetics , Transcription Factors/metabolism , Gene Expression Regulation, Plant , Indoleacetic Acids/metabolism , Solanum lycopersicum/physiology , Multigene Family , Mutagenesis, Site-Directed , Phylogeny , Plant Proteins/genetics , Promoter Regions, Genetic , Signal Transduction , Transcription Factors/genetics
14.
BMC Syst Biol ; 5: 55, 2011 Apr 19.
Article in English | MEDLINE | ID: mdl-21504591

ABSTRACT

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases. RESULTS: Using a compiled dataset containing 1,614 associations between 671 domains and 1,145 disease phenotypes, we demonstrate the effectiveness of the proposed approach through three large-scale leave-one-out cross-validation experiments (random control, simulated linkage interval, and genome-wide scan), and we do so in terms of three criteria (precision, mean rank ratio, and AUC score). We further show that the proposed approach is robust to the parameters involved and the underlying domain-domain interaction network through a series of permutation tests. Once having assessed the validity of this approach, we show the possibility of ab initio inference of domain-disease associations and gene-disease associations, and we illustrate the strong agreement between our inferences and the evidences from genome-wide association studies for four common diseases (type 1 diabetes, type 2 diabetes, Crohn's disease, and breast cancer). Finally, we provide a pre-calculated genome-wide landscape of associations between 5,490 protein domains and 5,080 human diseases and offer free access to this resource. CONCLUSIONS: The proposed approach effectively ranks susceptible domains among the top of the candidates, and it is robust to the parameters involved. The ab initio inference of domain-disease associations shows strong agreement with the evidence provided by genome-wide association studies. The predicted landscape provides a comprehensive understanding of associations between domains and human diseases.


Subject(s)
Bayes Theorem , Systems Biology/methods , Area Under Curve , Breast Neoplasms/metabolism , Crohn Disease/metabolism , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Genome , Genome-Wide Association Study , Humans , Models, Statistical , Phenotype , Protein Interaction Mapping , Protein Structure, Tertiary , Regression Analysis
15.
BMC Bioinformatics ; 12 Suppl 1: S11, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21342540

ABSTRACT

BACKGROUND: The identification of genes responsible for human inherited diseases is one of the most challenging tasks in human genetics. Recent studies based on phenotype similarity and gene proximity have demonstrated great success in prioritizing candidate genes for human diseases. However, most of these methods rely on a single protein-protein interaction (PPI) network to calculate similarities between genes, and thus greatly restrict the scope of application of such methods. Meanwhile, independently constructed and maintained PPI networks are usually quite diverse in coverage and quality, making the selection of a suitable PPI network inevitable but difficult. METHODS: We adopt a linear model to explain similarities between disease phenotypes using gene proximities that are quantified by diffusion kernels of one or more PPI networks. We solve this model via a Bayesian approach, and we derive an analytic form for Bayes factor that naturally measures the strength of association between a query disease and a candidate gene and thus can be used as a score to prioritize candidate genes. This method is intrinsically capable of integrating multiple PPI networks. RESULTS: We show that gene proximities calculated from PPI networks imply phenotype similarities. We demonstrate the effectiveness of the Bayesian regression approach on five PPI networks via large scale leave-one-out cross-validation experiments and summarize the results in terms of the mean rank ratio of known disease genes and the area under the receiver operating characteristic curve (AUC). We further show the capability of our approach in integrating multiple PPI networks. CONCLUSIONS: The Bayesian regression approach can achieve much higher performance than the existing CIPHER approach and the ordinary linear regression method. The integration of multiple PPI networks can greatly improve the scope of application of the proposed method in the inference of disease genes.


Subject(s)
Bayes Theorem , Phenotype , Protein Interaction Mapping/methods , Computational Biology/methods , Humans , Linear Models , Proteins/analysis
16.
Planta ; 231(4): 887-99, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20183921

ABSTRACT

Chinese bayberry (Myrica rubra) is a fruit crop with cultivars producing fruit ranging from white (Shuijing, SJ) to red (Dongkui, DK) and dark red-purple (Biqi, BQ), as a result of different levels of anthocyanin accumulation. Genes encoding the anthocyanin biosynthesis enzymes chalcone synthase, chalcone isomerase, flavanone 3-hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS) and UDPglucose: flavonoid 3-O-glucosyltransferase (UFGT), as well as MrMYB1, a R2R3 MYB transcription factor homologous to known activators of anthocyanin biosynthesis, were isolated from ripe fruit of BQ. Differences in mRNA abundance of MrF3H, MrF3'H, MrDFR1, MrANS and MrUFGT were highly correlated with differential accumulation of anthocyanins between cultivars, suggesting coordinated regulation by transcription factors. The transcript level of MrMYB1 was strongly associated with the anthocyanin content in ripe fruit of the three cultivars, as well as different anthocyanin containing tissues of BQ fruit. Fruit bagging strongly inhibited anthocyanin accumulation in fruit as well as the expression of all anthocyanin biosynthetic genes and MrMYB1. Overexpression of MrMYB1 stimulated both anthocyanin accumulation and activated an Arabidopsis-DFR promoter in tobacco (Nicotiana tabacum). MrMYB1d, an allele with a 1 bp deletion at nucleotide 30 of coding sequence, was observed in SJ and DK fruit, suggesting that a nonsense mutation of the MYB1 protein may be responsible for no or low expression of MYB1 in the white and red fruit. These results show that coordinated expression of multiple biosynthetic genes is involved in anthocyanin accumulation in Chinese bayberry fruit, and this is regulated by MrMYB1.


Subject(s)
Anthocyanins/biosynthesis , Fruit/metabolism , Gene Expression Regulation, Plant , Myrica/metabolism , Plant Proteins/metabolism , Transcription Factors/metabolism , Amino Acid Sequence , Codon, Nonsense/genetics , Fruit/genetics , Molecular Sequence Data , Myrica/genetics , Phylogeny , Plant Proteins/chemistry , Plant Proteins/genetics , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Polymerase Chain Reaction , Sequence Homology, Amino Acid , Nicotiana/genetics , Nicotiana/metabolism , Transcription Factors/chemistry , Transcription Factors/genetics
17.
Biomed Chromatogr ; 21(7): 755-61, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17385800

ABSTRACT

Simple and accurate HPLC methods were developed for the determination of oleanolic acid (OA), ursolic acid (UA) and amygdalin in loquat (Eriobotrya japonica Lindl.) flower, which is commonly used for the treatment of various diseases as a traditional Chinese medicine. HPLC assay was performed on a reversed-phase C(18) column and all three compounds were detected at 210 nm with a flow rate of 1.0 mL/min. The mobile phase consisted of methanol (A) and 0.03 mol/L phosphate buffer (pH 2.8) (B) with a ratio of 88:12 (A:B, v/v) for simultaneous detection of OA and UA, and 25:75 (A:B, v/v) for detection of amygdalin. The established methods showed good precision and accuracy with overall intra-day and inter-day variation of 0.99-3.55 and 1.05-4.05%, respectively, and overall recoveries of 97.37-99.32% for the three compounds. Application of these methods to determine the OA, UA and amygdalin contents in loquat flower showed that cultivar had a minor effect on the contents of all three compounds, with average amounts of 0.38-0.51 mg OA/g dry weight (DW), 2.15-2.68 mg UA/g DW and 1.23-1.56 mg amygdalin/g DW among five loquat cultivars tested. However, developmental stages and flower tissues showed significant effect on the contents of all three bioactive components.


Subject(s)
Amygdalin/analysis , Chromatography, High Pressure Liquid/methods , Eriobotrya/chemistry , Flowers/chemistry , Oleanolic Acid/analysis , Triterpenes/analysis , Reproducibility of Results , Spectrophotometry, Ultraviolet , Ursolic Acid
18.
Article in Chinese | MEDLINE | ID: mdl-16121014

ABSTRACT

Harvested fruits of three Chinese bayberry (Myrica rubra Sieb. & Zucc.) varieties, i.e. "Biqi", "Dongkui" and "Zaodamei" which were divided into three maturities (designated as "Immature", "Mature" and "Ripe") according to fruit colour, were investigated for the changes in climacteric pattern and quality at 20 degrees C. Respiration rate and ethylene production rate were underwent 3 h during 48 h storage. Our result showed that both Immature and Mature fruits underwent rises in respiration and ethylene production rate of a climacteric rise, but no such peak was observed in Ripe fruit (Fig.1 and 2). Total soluble solids (TSS) contents increased with maturity and decreased over the 48 h at 20 degrees C (Fig.3); titratable acidity (TA) decreased with the maturity and throughout 48 h storage period (Fig.4). In "Biqi" Chinese bayberry fruit, PAL activities increased in Immature and Mature fruit, but, it decreased in Ripe fruit during the storage period; the change in Cy-3-Glu with fruit ripening was consistent with PAL activities (Table 1); there was significant positive correlation between CIRG (Color Index for Red Grape) values and Cy-3-Glu content (r=0.96**). This study provides important information on the postharvest behaviour of Chinese bayberry fruit, and our result shows that it is climacteric fruit.


Subject(s)
Cell Respiration/physiology , Ethylenes/metabolism , Fruit/metabolism , Myrica/metabolism , Fruit/standards , Quality Control , Time Factors
19.
Article in Chinese | MEDLINE | ID: mdl-15643090

ABSTRACT

According to the conserved amino acid sequence from ethylene receptors in other plants, a pair of degenerate primers was designed and a 657-bp cDNA fragment encoding an ethylene receptor fruit was obtained by RT-PCR from ripening kiwifruit (Actinidia deliciosa cv. Bruno) (Fig. 1). The cDNA fragment encoding 219 amino acids was named Ad-ETR1, and its sequences shared high similarity at both nucleotide and polypeptide level with the sequences from the plants of Arabidopsis, tomato, persimmon, avocado, citrus and peach (Fig. 2, Table 1). Northern blot analysis indicated that the levels of Ad-ETR1 mRNA increased during kiwifruit ripening and reached peak at 144 h after treatment, then dropped immediately. The expression of Ad-ETR1 could be induced by ethylene treatment, while acetylsalicylic acid (ASA) treatment inhibited its expression (Fig. 4). In consistency with the changes of Ad-ETR1 mRNA, ethylene or ASA treatment had marked effects on the kiwifruit ethylene production and fruit softening (Fig. 3). The significance of these results was discussed.


Subject(s)
Actinidia/genetics , Fruit/genetics , Plant Proteins/genetics , Receptors, Cell Surface/genetics , Amino Acid Sequence , Base Sequence , Blotting, Northern , Cloning, Molecular , Molecular Sequence Data , Plant Proteins/chemistry , Receptors, Cell Surface/chemistry , Reverse Transcriptase Polymerase Chain Reaction
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