RESUMO
Microbial natural products represent a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class that include antibiotics, immunosuppressants, anticancer agents, toxins, siderophores, pigments, and cytostatics. The discovery of novel NRPs remains a laborious process because many NRPs consist of nonstandard amino acids that are assembled by nonribosomal peptide synthetases (NRPSs). Adenylation domains (A-domains) in NRPSs are responsible for selection and activation of monomers appearing in NRPs. During the past decade, several support vector machine-based algorithms have been developed for predicting the specificity of the monomers present in NRPs. These algorithms utilize physiochemical features of the amino acids present in the A-domains of NRPSs. In this article, we benchmarked the performance of various machine learning algorithms and features for predicting specificities of NRPSs and we showed that the extra trees model paired with one-hot encoding features outperforms the existing approaches. Moreover, we show that unsupervised clustering of 453â560 A-domains reveals many clusters that correspond to potentially novel amino acids. While it is challenging to predict the chemical structure of these amino acids, we developed novel techniques to predict their various properties, including polarity, hydrophobicity, charge, and presence of aromatic rings, carboxyl, and hydroxyl groups.
Assuntos
Aminoácidos , Genoma Microbiano , Algoritmos , Família Multigênica , PeptídeosRESUMO
CONTEXT: Candidatus-phytoplasma castaneae has been found as the causal agent of the Chinese chestnut yellow crinkle disease. However, the ecological impact of the disease on microbiota of chestnut trees is unknown. AIMS: The study aim was to clarify difference attributes in microbial community structure of asymptomatic and symptomatic chestnut leaves and twigs for chestnut tree health in orchard. METHODS: Sample collections were conducted with both symptomatic and asymptomatic chestnut trees. Total DNA was extracted. Fungal ITS rDNA and bacterial 16S rDNA were amplified. The PCR products were sequenced with Illumina HiSeq. Platform. RESULTS: A total number of 852 fungal and 1156 bacterial OTUs (operational taxonomic units) were detected. The asymptomatic samples had a higher fungal and bacterial diversity than symptomatic ones. Non-metric multidimensional scaling (NMDS) analysis showed microbial communities among symptomatic and asymptomatic leaves and twigs samples formed individual cluster. Overall, Ascomycota and Proteobacteria were the most abundant fungal and bacterial phyla, respectively. Significantly different taxa playing key roles for each microbiota structure were identified. In symptomatic trees, microbial groups of plant pathogens were more abundant. CONCLUSION: Our results demonstrated that the phytoplasma pathogen may exert significant influence on the microbial community structure. The study will provide further fundamental clues for the little studied phytoplasma pathogens effects on host microbiota, phytoplasma pathogen control strategies.
Assuntos
Ascomicetos , Microbiota , Ascomicetos/genética , Bactérias/genética , China , ÁrvoresRESUMO
Raw Moutan Cortex (RMC) and Processed Moutan Cortex (PMC) have a long history of use in China and other Asian countries. In this study, a rapid and accurate ultra-high-pressure liquid chromatography coupled with diode array detector (UHPLC-DAD) method was developed and validated for the simultaneous determination of nine absorbed compounds of RMC/PMC. After extraction by protein precipitation with methanol from plasma, the analytes were separated on an Acquity UPLC® BEH Shield RP18 column (2.1 × 100 mm, 1.7 µm, Waters, USA). Acetonitrile (A) and 0.1% (v/v) formic acid in water (B) were selected as the mobile phase to perform gradient elution. The linearity of nine analytes was >0.9915. The intra- and inter-assay precision (RSD) values were within 11.18%, and accuracy ranged from 91.32 to 101.29%. Suitable stability, matrix effect and extraction recoveries were also obtained. The validated method was applied to compare the pharmacokinetics of RMC and PMC in Blood-Heat and Hemorrhage Syndrome Model and normal rats. The results revealed that processing and the pathological state could influence the pharmacokinetic characteristics of compounds in RMC/PMC. The study willbe useful for further studies on pharmacokinetics and clinical application of raw and processed Moutan Cortex.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas , Hemorragia/metabolismo , Medicina Tradicional Chinesa , Paeonia , Espectrometria de Massas em Tandem/métodos , Animais , Benzoatos/sangue , Benzoatos/farmacocinética , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Glucosídeos/sangue , Glucosídeos/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Terpenos/sangue , Terpenos/farmacocinéticaRESUMO
OBJECTIVE: An association of Epstein-Barr virus (EBV) infection with breast carcinoma (BC) risk has so far been disputed in the literature. Therefore, we performed a meta-analysis to clarify this relationship. MATERIALS AND METHODS: An electronic database search for eligible case-control studies was performed using PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang Data until May 17, 2018. The pooled OR and 95% CI were used to estimate the relationship between EBV infection and BC risk using a fixed or random-effects model depending on heterogeneity. Subgroup analysis and meta-regression were used to explore the heterogeneity. Publication bias was assessed using Egger's and Harbord's tests. RESULTS: A total of 16 studies with 1,279 patients and 814 controls were reviewed based on our inclusion and exclusion criteria. Compared with the control group, EBV infection had a significant association with BC risk (OR 4.75, 95% CI 2.53-8.92, p < 0.01) with significant heterogeneity observed (I2 = 65.3%). The subgroup analysis revealed that region and tissue type might explain potential sources of heterogeneity. The sensitivity analyses yielded stable results. No significant publication bias was observed. CONCLUSION: The current results suggest that EBV infection is significantly associated with increased risk of BC.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/virologia , Infecções por Vírus Epstein-Barr/complicações , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Fatores de RiscoRESUMO
Plant endophytes play a crucial role in plant growth, health and ecological function. Jingbai pear (the best quality cultivar of Pyrus ussuriensi Maxim. ex Rupr.) has important ecological and economic value in north China. Conversation of its genetics has great meanings to pear genus (Pyrus L.). However, the bacterial community associated with the cultivar remains unknown. In this study, the structure of endophytic bacterial communities associated with different tissues and soil of Jingbai Pear trees was analyzed with Illumina Miseq sequencing of bacterial 16S rDNA. This is the first report on bacterial microbiome associated with Jingbai pear. Our results demonstrated that different tissues harbored a unique bacterial assemblage. Interestingly, Cyanobacteria was the most abundant phylum, followed by Proteobacteria and Actinobacteria. Samples from three different sites (soils) had significant differences in microbial communities structure. Redundancy analysis (RDA) showed that the bacterial community structure correlated significantly with soil properties-temperature, pH, nitrogen and carbon contents. The conclusion could facilitate to understand the interaction and ecological function of endophytic bacteria with host Jingbai pear trees, so as to benefit the pear variety genetic resource conservation and protection.
Assuntos
Bactérias/isolamento & purificação , Pyrus/microbiologia , Actinobacteria/isolamento & purificação , Bactérias/genética , China , Cianobactérias/isolamento & purificação , DNA Ribossômico/química , Endófitos , Microbiota , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/química , Microbiologia do Solo , Árvores/microbiologiaRESUMO
BACKGROUND: Clinical characteristics (taxonomy, virulence genes and antimicrobial resistance ) of Aeromonas in isolated from extra-intestinal and intestinal infections were investigated to describe epidemiology, associated virulence factors and optimal therapy options. METHODS: Clinical samples (n = 115) of Aeromonas were collected from a general hospital in Beijing between the period 2015 and 2017. Taxonomy was investigate by Multilocus phylogenetic analysis (MLPA), 10 putative virulence factors by use of polymerase chain reaction (PCR) and antimicrobial resistance to 15 antibiotics by use of the microbroth dilution method. RESULTS: The most common species of Aeromonas detected in samples of intestinal tract included; A. caviae (43.9%), A. veronii (35.7%), and A. dhakensis (12.2%). Prevalent species of Aeromonas collected from extra-intestinal infections included; A. hydrophila (29.4%), A. caviae (29.4%), and A. dhakensis (23.5%). A. hydrophila were detected in 1% of stool samples and 29.4% (5/17) of extra-intestinal infections. A. hydrophila strains in extra-intestinal infections were related to malignancy. The most common medical conditions among patients with Aeromonas infections included malignancy and liver-transplant related cholecystitis. Multiple drug resistance (MDR) was prevalent in extra-intestinal isolates (82.3%, 14/17) and was greater than the prevalence in intestinal isolates (30.6%, 30/98) (P < 0.05). Resistant rates of extra-intestinal isolates were 70.6, 35.3, 23.5 and 5.9% for ceftriaxone, ciprofloxacin, gentamicin and imipenem, respectively, and were higher than found in previous studies. Despite differences in the number and type of virulence genes among samples of Aeromonas, no significant correlation was found between invasion and virulent genes in intestinal or extra-intestinal infections. CONCLUSIONS: Overall results of this study support a role for Aeromonas spp. as a potential causative infectious agent of gastroenteritis, and malignancy, liver cirrhosis, post liver transplantation in immunocompromised patients. A. hydrophila was more prevalent in samples of extra-intestinal infections when compared to samples of intestinal infections, and was especially prominent in samples of patients presenting with malignancy. Aeromonas isolates from extra-intestinal samples had high rates of drug resistance but 3rd generation cephalosporins, fluoroquinolones and aminoglycosides remain as options to treat severe diarrhea. However, increasing MDR of extra-intestinal infection samples warrants monitoring.
Assuntos
Aeromonas/classificação , Aeromonas/isolamento & purificação , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/microbiologia , Enteropatias/microbiologia , Infecções Intra-Abdominais/microbiologia , Fatores de Virulência/genética , Adolescente , Adulto , Aeromonas/efeitos dos fármacos , Aeromonas/genética , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , China/epidemiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Feminino , Gastroenterite/tratamento farmacológico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Enteropatias/tratamento farmacológico , Enteropatias/epidemiologia , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogenia , Prevalência , Virulência/genética , Adulto JovemRESUMO
Poplar are important forestry species in China, but the Botryosphaeria dothidea pathogen causes serious economic losses worldwide. To identify candidate B. dothidea resistance proteins and explore the molecular mechanisms involved in poplar-pathogen interactions, proteomic responses of stem samples from resistant and susceptible poplar ecotypes to B. dothidea were investigated using nanoflow liquid chromatography-tandem mass spectrometry with label-free quantitative analysis. We identified 588 proteins, divided into 21 biological process categories including 48 oxidoreductases, 72 hydrolytic enzymes, 80 metabolic enzymes, and 29 proteins of unknown function. Differential proteome analysis revealed large differences between resistant Populus tomentosa Carr and susceptible Populus beijingensis Hsu ecotypes before and after inoculation. Among 102 identified proteins, 22 were highly upregulated in the resistant genotype but downregulated in the susceptible genotype. Proteins induced in P. tomentosa Carr in response to B. dothidea are associated with plant defenses including oxidoreductase activity (catalase, isocitrate dehydrogenase, and superoxide dismutase), phenylpropanoid biosynthesis and phenylalanine metabolism (alcohol dehydrogenase), photosynthesis (ATP synthase subunit alpha, ATP synthase gamma chain, photosystem I P700 chlorophyll a apoprotein A2, photosystem II CP47 chlorophyll apoprotein), carbon fixation (pyruvate kinase, triosephosphate isomerase, malic enzyme, phosphoglycerate kinase, ribulose-1,5-bisphosphate carboxylase, and ribulose bisphosphate carboxylase small chain), and glycolysis/gluconeogenesis (fructose-bisphosphate aldolase). Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 168 proteins related to metabolic pathways, 41 proteins related to the biosynthesis of phenylpropanoids, and 36 proteins related to the biosynthesis of plant hormones, the biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid, and photosynthesis in response to B. dothidea. Our findings provide insight into plant-pathogen interactions in resistant and susceptible poplar ecotypes infected with B. dothidea and could assist the development of novel strategies for fighting poplar canker disease.
Assuntos
Ascomicetos , Populus , Proteômica , Ascomicetos/fisiologia , China , Ecótipo , Doenças das Plantas/microbiologia , Populus/classificação , Populus/microbiologiaRESUMO
For matching the new fungal nomenclature to abolish pleomorphic names for a fungus, a genus Pseudocercospora s. str. was suggested to host holomorphic Pseudocercosproa fungi. But the Pseudocercosproa fungi need extra phylogenetic loci to clarify their taxonomy and diversity for their existing and coming species. Internal transcribed spacer 2 (ITS2) secondary structures have been promising in charactering species phylogeny in plants, animals and fungi. In present study, a conserved model of ITS2 secondary structures was confirmed on fungi in Pseudocercospora s. str. genus using RNAshape program. The model has a typical eukaryotic four-helix ITS2 secondary structure. But a single U base occurred in conserved motif of U-U mismatch in Helix 2, and a UG emerged in UGGU motif in Helix 3 to Pseudocercospora fungi. The phylogeny analyses based on the ITS2 sequence-secondary structures with compensatory base change characterizations are able to delimit more species for Pseudocercospora s. str. than phylogenic inferences of traditional multi-loci alignments do. The model was employed to explore the diversity of endophytic Pseudocercospora fungi in poplar trees. The analysis results also showed that endophytic Pseudocercospora fungi were diverse in species and evolved a specific lineage in poplar trees. This work suggested that ITS2 sequence-structures could become as additionally significant loci for species phylogenetic and taxonomic studies on Pseudocerospora fungi, and that Pseudocercospora endophytes could be important roles to Pseudocercospora fungi's evolution and function in ecology.
Assuntos
Ascomicetos/genética , DNA Espaçador Ribossômico/química , Populus/microbiologia , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Endófitos/genética , Endófitos/isolamento & purificação , Conformação de Ácido Nucleico , FilogeniaRESUMO
Raw Arecae Semen, the seed of Areca catechu L., as well as Arecae Semen Tostum and Arecae semen carbonisata are traditionally processed by stir-baking for subsequent use in a variety of clinical applications. These three Arecae semen types, important Chinese herbal drugs, have been used in China and other Asian countries for thousands of years. In this study, the sensory technologies of a colorimeter and sensitive validated high-performance liquid chromatography with diode array detection were employed to discriminate raw Arecae semen and its processed drugs. The color parameters of the samples were determined by a colorimeter instrument CR-410. Moreover, the fingerprints of the four alkaloids of arecaidine, guvacine, arecoline and guvacoline were surveyed by high-performance liquid chromatography. Subsequently, Student's t test, the analysis of variance, fingerprint similarity analysis, hierarchical cluster analysis, principal component analysis, factor analysis and Pearson's correlation test were performed for final data analysis. The results obtained demonstrated a significant color change characteristic for components in raw Arecae semen and its processed drugs. Crude and processed Arecae semen could be determined based on colorimetry and high-performance liquid chromatography with a diode array detector coupled with chemometrics methods for a comprehensive quality evaluation.
Assuntos
Areca/química , Medicamentos de Ervas Chinesas/análise , China , Cromatografia Líquida de Alta Pressão , Análise de Componente Principal , Controle de Qualidade , Sementes/químicaRESUMO
Nosocomial candidemia extends the length of hospital stay, increases the costs of medical care, and is associated with a high mortality rate. Epidemiological data that assist in the choice of initial therapy may help to improve the prognosis. The present study was undertaken to investigate the epidemiology of nosocomial candidemia and identify risk factors for nosocomial candidemia caused by C. albicans and non-albicans Candida species (NAC). A retrospective chart review was undertaken to analyze cases of nosocomial candidemia treated at the Beijing Friendship Hospital between January 2008 and December 2012. All cases of candidemia were identified using the previously published criteria. Among 106 patients analyzed, 53.8% had nosocomial candidemia caused by NAC. Candida albicans was the most common causative agent, accounting for 46.2% of all cases, followed by C. glabrata (25.5%), C. tropicalis (15.1%), C. parapsilosis (10.4%) and C. Krusei (0.9%). Comparison of nosocomial C. albicans and NAC candidemia by multivariate logistic regression showed that factors independently associated with nosocomial NAC candidemia included exposure to azole agents (odds ratio [OR]: 3.359; 95% confidence interval [CI]: 1.136-10.154; P = .031) and artificial surgical implants (OR: 37.519; 95% CI: 2.5-562.998; P = .009). A significant risk factor for nosocomial C. albicans candidemia was cancer surgery (OR: 0.075; 95% CI: 0.013-0.437; P = .004). Clinical and epidemiological differences in the risk factors between nosocomial candidemia caused by C. albicans and NAC should be considered when selecting an initial antifungal regimen for the treatment of adult patients. This should be undertaken before the availability of species identification and/or antifungal susceptibility results.
Assuntos
Candida/classificação , Candida/isolamento & purificação , Candidemia/epidemiologia , Candidemia/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Candida albicans can form biofilms on intravenous catheters; this process plays a key role in the pathogenesis of catheter infections. This study evaluated the effect of human serum (HS) on C. albicans biofilm formation and the expression of adhesion-related genes in vitro. A C. albicans laboratory strain (ATCC90028) and three clinical strains were grown for 24 h in RPMI 1640 supplemented with HS or RPMI 1640 alone (as a control). The growth of biofilm cells of four strains was monitored by a Live Cell Movie Analyzer, and by XTT reduction assay. The expression of the adhesion-related genes BCR1, ALS1, ALS3, HWP1 and ECE1 was analyzed by RT-PCR at three time points (60 min, 90 min, and 24 h). RESULTS: In the adhesion phase, C. albicans cells kept a Brownian movement in RPMI medium containing HS until a large number of germ tubes were formed. In the control group, C. albicans cells quickly adhered to the bottom of the reaction plate. Compared with RPMI 1640, medium supplemented with 3-50% HS caused a significant decrease in biofilm development (all p < 0.001). However, the presence of HS had no significant inhibitory effect on the pre-adhered biofilms (all p > 0.05). Biofilm formation was also inhibited by heat-inactivated and proteinase K pre-treated HS. The presence of 50% HS did not significantly affect the planktonic growth of C. albicans (p > 0.05). At three time points, HS inhibited expression of the ALS1 and ALS3 genes and promoted expression of the HWP1 and ECE1 genes. Significant up-regulation of BCR1 was observed only at the 90-min point. CONCLUSIONS: Human serum reduces biofilm formation by inhibiting the adhesion of C. albicans cells. This response may be associated with the down-regulation of adhesion-related genes ALS1, ALS3 and BCR1. The inhibitory serum component is protease-resistant and heat stable.
Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/imunologia , Candida albicans/fisiologia , Adesão Celular/efeitos dos fármacos , Soro/imunologia , Candida albicans/genética , Proteínas Fúngicas/biossíntese , Perfilação da Expressão Gênica , Genes Fúngicos , Humanos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Human papillomavirus (HPV) is associated with several disorders of the genital tract, skin, and oropharynx. This study investigated the prevalence of infection by 37 HPV genotypes among women of the Beijing area in China. Cervical specimens from 1,082 patients and 165 healthy controls were tested for HPV genotypes using a chip hybridization assay. Based on the local pathology, patients were divided into cervicitis and cervical lesion groups. Overall HPV infection rates were 30.5% for the cervicitis group and 78.4% for the cervical lesion group; whereas infection rates for high-risk HPV types (i.e., those associated with cervical cancers) were 24.0% and 73.4%, respectively. The most common HPV genotypes were HPV 52, 16, 81, 58, and 18 in healthy controls, HPV 52, 61, 55, 16, and 53 in those with cervicitis, HPV 52, 16, 33, 39, and 58 in cervical intraepithelial neoplasia grade 1, HPV 16, 58, 31, 52, and 33 in cervical intraepithelial neoplasia grade 2 or grade 3, and HPV 16, 33, 18, 52, and 58 in cervical cancer. Established high-risk HPV showed two peaks, in patients aged 30-34 and 55-79 years. In Beijing, HPV 16, 52, 58, and 33 are the most prevalent HPV types in women with cervical lesions, which should affect development of a cervical cancer vaccination for local use.
Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Colo do Útero/patologia , Colo do Útero/virologia , China/epidemiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Prevalência , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer's disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.
Assuntos
Doença de Alzheimer , Bancos de Espécimes Biológicos , Endofenótipos , Estudo de Associação Genômica Ampla , Doença de Alzheimer/genética , Humanos , Fatores de Risco , Masculino , Feminino , Reino Unido/epidemiologia , Idoso , Predisposição Genética para Doença , Herança Multifatorial/genética , Idoso de 80 Anos ou maisRESUMO
Type 1 polyketides are a major class of natural products used as antiviral, antibiotic, antifungal, antiparasitic, immunosuppressive, and antitumor drugs. Analysis of public microbial genomes leads to the discovery of over sixty thousand type 1 polyketide gene clusters. However, the molecular products of only about a hundred of these clusters are characterized, leaving most metabolites unknown. Characterizing polyketides relies on bioactivity-guided purification, which is expensive and time-consuming. To address this, we present Seq2PKS, a machine learning algorithm that predicts chemical structures derived from Type 1 polyketide synthases. Seq2PKS predicts numerous putative structures for each gene cluster to enhance accuracy. The correct structure is identified using a variable mass spectral database search. Benchmarks show that Seq2PKS outperforms existing methods. Applying Seq2PKS to Actinobacteria datasets, we discover biosynthetic gene clusters for monazomycin, oasomycin A, and 2-aminobenzamide-actiphenol.
Assuntos
Espectrometria de Massas , Família Multigênica , Policetídeo Sintases , Policetídeos , Policetídeos/metabolismo , Policetídeos/química , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Espectrometria de Massas/métodos , Mineração de Dados/métodos , Aprendizado de Máquina , Actinobacteria/genética , Actinobacteria/metabolismo , Genoma Bacteriano , Algoritmos , Produtos Biológicos/química , Produtos Biológicos/metabolismoRESUMO
Populus euphratica Olivier is widely established in arid and semiarid regions but lags in the availability of transcriptomic resources in response to water deficiency. To investigate the mechanisms that allow P. euphratica to maintain growth in arid regions, the responses of the plant to soil water deficit were analyzed at a systems level using physiological and pyrosequencing approaches. We generated 218,601 and 287,120 reads from non-stressed control and drought-stressed P. euphratica leaves respectively, totaling over 200 million base pairs. After assembly, 24,013 transcripts were yielded with an average length of 1,128 bp. We determined 2,279 simple sequence repeats, which may have possible information for understanding drought adaption of woody plants. Stomatal closure was inhibited under moderate drought to maintain a relatively high rate of CO2 assimilation and water transportation, which was supposed to be important for P. euphratica to maintain normal growth and develop vigorous root systems in an adverse environment. This was accompanied by strong transcriptional remodeling of stress-perception, signaling and transcription regulation, photoprotective system, oxidative stress detoxification, and other stress responsive genes. In addition, genes involved in stomatal closure inhibition, ascorbate-glutathione pathway and ubiquitin-proteasome system that may specially modulate the drought stress responses of P. euphratica are highlighted. Our analysis provides a comprehensive picture of how P. euphratica responds to drought stress at physiological and transcriptome levels which may help to understand molecular mechanisms associated with drought response and could be useful for genetic engineering of woody plants.
Assuntos
Desidratação/fisiopatologia , Regulação da Expressão Gênica de Plantas/fisiologia , Populus/fisiologia , Transcriptoma/fisiologia , Simulação por Computador , Desidratação/genética , Secas , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Genes de Plantas/fisiologia , Repetições de Microssatélites/genética , Repetições de Microssatélites/fisiologia , Polimorfismo Genético/genética , Populus/genética , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma/genética , Árvores/genética , Árvores/fisiologiaRESUMO
PROBLEM: Although physical restraint practices and psychotropic/sedative pro re neta (PRN, as needed) medications have been commonly used for managing inpatient aggression, little is known about the characteristics of adolescents who receive them in psychiatric adolescent inpatient units. We aimed to determine the relationship between the use of physical restraints and psychotropic/sedative PRN medications, and to characterize individual attributes, substance use, clinical factors, and time of the first restraint episodes of the use of physical restraints and psychotropic/sedative PRN medications. METHODS: A retrospective case-control study approach was used with the data from electronic health records at a pediatric psychiatric hospital in the United States. Descriptive statistics, χ2 , multivariate logistic regression, and Cox proportional hazard model were used. FINDINGS: Participants of younger age and participants with a longer length of stay were significantly associated with the use of physical restraints and psychotropic/sedative PRN medications, although the substance-related risks were not significantly associated with the use of restraints. Physical restraints were more likely to have occurred soon after the admission and tapered off as the length of stay increased. CONCLUSIONS: This study provides important information in understanding the risk factors of the use of restraints and psychotropic/sedative PRN medications in psychiatric adolescent inpatient units.
Assuntos
Transtornos Mentais , Restrição Física , Humanos , Adolescente , Criança , Pacientes Internados , Estudos Retrospectivos , Estudos de Casos e Controles , Psicotrópicos/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Hospitais Psiquiátricos , Transtornos Mentais/tratamento farmacológicoRESUMO
By activating protective pathways, tumour cells are not only capable of survival in stress, but often associated with increased aggressiveness and metastasis. Activating transcription factor 4 (ATF4) is a major coordinator of tumour cell survival in stress and is commonly overexpressed in tumours. Numerous studies suggested that the ATF4 is a potential therapeutic target for cancer. In this report, we describe that a small ribosomal peptide, RPL41, induced rapid ATF4 degradation. By immunofluorescence staining, RPL41 induced ATF4 relocation from nuclei to cytoplasm, where ATF4 co-stained with a proteasome marker; the RPL41-induced ATF4 relocation and degradation were blocked by the proteasome inhibitor MG132. An in vivo phosphorylation study showed that RPL41 induced ATF4 phosphorylation and serine 219 of ATF4 was essential for RPL41-induced ATF4 degradation. Cells with RPL41 knockdown had significantly increased ATF4, suggesting that RPL41 could play a physiological role in regulating the cellular ATF4 level. RPL41 was capable of inducing tumour cell death and cell cycle arrest; at low dose, RPL41 sensitized tumour cells A549 to the DNA damage agent cisplatin. These studies suggest that RPL41, a small peptide that is chemically synthesizable and capable of self-cell penetration, may have potential as an anti-ATF4 agent for cancer therapy.
Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Neoplasias/metabolismo , Proteínas Ribossômicas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Imunofluorescência , Humanos , Fosforilação , Transporte Proteico/fisiologia , RNA Interferente Pequeno , Estresse Fisiológico/fisiologia , TransfecçãoRESUMO
The human microbiome is a complex community of microorganisms, their enzymes, and the molecules they produce or modify. Recent studies show that imbalances in human microbial ecosystems can cause disease. Our microbiome affects our health through the products of biochemical reactions catalyzed by microbial enzymes (microbial biotransformations). Despite their significance, currently, there are no systematic strategies for identifying these chemical reactions, their substrates and molecular products, and their effects on health and disease. We present TransDiscovery, a computational algorithm that integrates molecular networks (connecting related molecules with similar mass spectra), association networks (connecting co-occurring molecules and microbes) and knowledge bases of microbial enzymes to discover microbial biotransformations, their substrates, and their products. After searching the metabolomics and metagenomics data from the American Gut Project and the Global Foodomic Project, TranDiscovery identified 17 potentially novel biotransformations from the human gut microbiome, along with the corresponding microbial species, substrates, and products.
RESUMO
Ophiostomatalean fungi usually facilitate bark beetles to infest tree hosts and seriously endanger the health of coniferous forests. Tomicus pilifer Spessivtsev is a common endemic bark beetle in Asia and primarily threatens Pinus koraiensis. Tomicus species have similar morphology; however, they can be differentiated by their genetic characteristics through phylogenetic analyses. To date, the 28S rDNA sequence of T. pilifer and the diversity of ophiostomatalean fungi associated with T. pilifer have not been reported. In this study, we aimed to clarify the taxonomic status of T. pilifer and identify ophiostomatalean fungi associated with T. pilifer infesting P. koraiensis in northeastern China. In total, 315 ophiostomatalean fungal strains were isolated from 62 adults of T. pilifer and 220 tissue samples from T. pilifer galleries in Jilin Province. Thirty-five representative strains were further identified by comparing their morphological and physiological characteristics and conducting the phylogenetic analysis of ITS, ITS2-LSU, TUB2, and TEF1-α. We identified nine species of ophiostomatalean fungi belonging to four genera, which included six novel species (Ceratocystiopsis changbaiensis sp. nov., Leptographium linjiangense sp. nov., Leptographium qieshaoense sp. nov., Ophiostoma piliferi sp. nov., Ophiostoma tonghuaense sp. nov., and Ophiostoma yaluense sp. nov.), two previously described species (Graphilbum interstitiale and Ophiostoma fuscum), and one undefined specie (Ceratocystiopsis sp. 1). To the best of our knowledge, this is the first report of G. interstitiale and O. fuscum in China and the fungal diversity of ophiostomatalean in T. pilifer. The dominant species were O. piliferi and L. qieshaoense, representing 39.37% and 35.87% of the isolates, respectively. The results of this study provide valuable information on the symbiotic relationship between bark beetles and ophiostomatalean fungi.
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BACKGROUND: Raw Moutan Cortex (RMC) has been used in China and other Asian countries for thousands of years. Its medical application is the treatment of cooling blood and promoting blood circulation. However, its therapeutic mechanism is still undefined. METHODS: In this study, the pharmacokinetics strategy that integrated network analysis was employed to explore the mechanism of RMC in blood-heat and blood stasis syndrome (BHS) model rats. Firstly, Ultra-High performance Liquid Chromatography coupled with Diode Array Detector (UHPLC-DAD) method was developed to determine nine absorbed compounds in rat serum in BHS and normal rats after oral administration of RMC extract respectively. Then the pharmacology network was established based on the relationship between nine compounds absorbed into the blood and BHS targets. Finally, the predicted hub targets were validated experimentally in human umbilical vein endothelial cells (HUVECs). RESULTS: Pharmacokinetic study showed that the pharmacokinetic parameters of nine absorbed compounds had significant differences between BHS and normal groups (p < 0.05). Network analysis showed that 8 target genes, namely, F2, F10, F7, PLAU, MAPK14, MAPK10, AKT1, and NOS3 may be the primary targets regulated by RMC for the treatment of BHS. Among them, targets (F2, F10, F7 and MAPK14, MAPK10, AKT) and 4 active ingredients (paeonol, paeoniflorin, quercetin and oxypaeoniflorin) were selected for evaluating the reliability in vitro experiments, which revealed that the mechanism of RMC against BHS syndrome may inhibit inflammatory pathways and regulate coagulation cascades pathway for cooling and promoting blood circulation. CONCLUSION: The proposed pharmacokinetics study integrated network analysis strategy provides a combination method to explore the therapeutic mechanism of RMC on BHS.