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1.
Anticancer Res ; 40(5): 2675-2685, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366412

RESUMO

BACKGROUND/AIM: To evaluate the anti-cancer mechanism of N-Farnesyl-norcantharimide (NC15). MATERIALS AND METHODS: The viability of NC15-treated human leukemic Jurkat T (JKT) cells was assessed using the Kit-8 cell counting method. Flow cytometry analysis, human apoptosis antibody array assay, and whole genome sequencing were adopted to investigate the mechanism underlying the anti-cancer activity of NC15 in JKT cells. RESULTS: The growth inhibition rates of NC15 in JKT cells were about 80% and 95% after treatment with 8 µmol/l NC15 for 24 and 48 h, respectively. The percentages of NC15-treated JKT cells in the sub-G1 phase at 24 and 48 h were 22.0% and 34.3%, respectively, in contrast to the 1.5% in the control. Next-generation sequencing showed that many tumor suppressor genes (TSG) were up-regulated, while many genes associated with steroid biosynthesis, metabolic pathways, and fatty acid metabolism were down-regulated. CONCLUSION: NC15 can reduce the cell viability and increase the percentage of JKT cells in the sub-G1 phase by up-regulating TSG and related genes, and down-regulating the genes for steroid biosynthesis, metabolic pathways and fatty acid metabolism, instead of through apoptosis.


Assuntos
Cantaridina/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos/metabolismo , Genes Supressores de Tumor , Redes e Vias Metabólicas/genética , Esteroides/biossíntese , Linfócitos T/citologia , Regulação para Cima/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Cantaridina/química , Cantaridina/farmacologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Regulação para Baixo/genética , Humanos , Células Jurkat , Redes e Vias Metabólicas/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Regulação para Cima/genética
2.
Bioresour Technol ; 311: 123422, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32413636

RESUMO

The responses of microbial structures, functional profiles and metabolic pathways during nitrification to four C/N ratios (0, 5, 10 and 15) were investigated in four parallel SBRs denoted as S0, S5, S10, S15. Results indicated that microbial diversities were affected by C/N ratios, while the same dominant taxa were observed, mainly including Proteobacteria, Betaproteobacteria, Rhodocyclales, Rhodocyclaceae, Zoogloea. The unique biomarkers were identified in each sludge sample through LEfSe analysis. Functional genera/enzymes responsible for removing organics and nitrogen coexisted in four SBRs at different abundances, except for that ammonia oxidizing bacteria (AOB) Nitrosomonas (0.33%-0.66%) and ammonia monooxygenase (amo) (9.4 × 10-7-2.8 × 10-6) were only detected in S0. Moreover, PICRUSt analysis indicated similar overall patterns of metabolic pathways in four sludge samples. The network analysis revealed that total nitrogen removal positively correlated with hcp (Spearman's ρ of 0.853), and ammonia oxidizing rate was associated with amo (Spearman's ρ of 0.096).


Assuntos
Amônia , Nitrificação , Redes e Vias Metabólicas , Nitrogênio , Oxirredução , Esgotos
3.
BMC Bioinformatics ; 21(1): 130, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245365

RESUMO

BACKGROUND: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine. RESULTS: The results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation that mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures. CONCLUSIONS: The new visualization technique GEM-Vis introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types. The supplement includes a comprehensive user's guide and links to a series of tutorial videos that explain how to prepare model and data files, and how to use the software SBMLsimulator in combination with further tools to create similar animations as highlighted in the case studies.


Assuntos
Redes e Vias Metabólicas , Metabolômica/métodos , Plaquetas/metabolismo , Eritrócitos/metabolismo , Humanos , Metaboloma
4.
Chem Biol Interact ; 323: 109077, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32246921

RESUMO

7H-Dibenzo[c,g]carbazole (DBC), a local and systemic carcinogen in animal studies, is a common environmental pollutant. It generally co-occurs in a variety of organic complex mixtures derived from incomplete combustion of organic matter. Despite high lipophilicity, DBC is more water-soluble and faster metabolized than the homocyclic aromatics. Moreover, greater polarity, high bioaccumulation potential, and persistence in the environment may imply DBC's higher biological significance and impact on human health, even at lower concentrations. The biotransformation pathways of DBC are incompletely known and the ultimate carcinogenic metabolite(s) are not clearly identified as yet. Structure-biological studies suggest two ways of activation: at the ring carbon atoms and at the pyrrole nitrogen. It is supposed that the particular pathway of biotransformation might be connected with the tissue/organ specificity of DBC. Cytochrome P450 (CYP) family of enzymes plays a pivotal role in the metabolism of DBC; though, the one-electron activation and the aldo-keto reductase-catalyzed oxidation are also involved in metabolic activation. Additionally, DBC can be photoactivated even at physiologically relevant doses of UVA light due to the extended aromatic ring system resulting in strong genotoxicity and oxidative stress. The goal of this review is to summarize current knowledge on mechanisms of DBC activation and possible implications for toxicity, genotoxicity, and carcinogenicity.


Assuntos
Carbazóis/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Animais , Carbazóis/química , Carbazóis/metabolismo , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Humanos , Luz , Oxirredução , Relação Estrutura-Atividade
5.
BMC Bioinformatics ; 21(1): 140, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293238

RESUMO

BACKGROUND: High-throughput omics technologies have enabled the comprehensive reconstructions of genome-scale metabolic networks for many organisms. However, only a subset of reactions is active in each cell which differs from tissue to tissue or from patient to patient. Reconstructing a subnetwork of the generic metabolic network from a provided set of context-specific active reactions is a demanding computational task. RESULTS: We propose SWIFTCC and SWIFTCORE as effective methods for flux consistency checking and the context-specific reconstruction of genome-scale metabolic networks which consistently outperform the previous approaches. CONCLUSIONS: We have derived an approximate greedy algorithm which efficiently scales to increasingly large metabolic networks. SWIFTCORE is freely available for non-commercial use in the GitHub repository at https://mtefagh.github.io/swiftcore/.


Assuntos
Redes e Vias Metabólicas/genética , Software , Algoritmos , Genoma , Humanos
6.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1225-1231, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281329

RESUMO

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to "cytokine storm". "Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the "cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on "cytokine storm" according to the potential herbs in the "National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-ß-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.


Assuntos
Ácido Araquidônico/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Betacoronavirus , Humanos , Medicina Tradicional Chinesa , Redes e Vias Metabólicas , Pandemias
7.
Ecotoxicol Environ Saf ; 196: 110483, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247238

RESUMO

A study was performed to assess if nitrate reductase (NR) participated in brassinosteroid (BR)-induced cadmium (Cd) stress tolerance primarily by accelerating the ascorbate-glutathione (AsA-GSH) cycle. Prior to initiating Cd stress (CdS), the pepper plants were sprayed with 0.5 µM 24-epibrassinolide (EBR) every other day for 10 days. Thereafter the seedlings were subjected to control or CdS (0.1 mM CdCl2) for four weeks. Cadmium stress decreased the plant growth related attributes, water relations as well as the activities of monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR), but enhanced proline content, leaf Cd2+ content, oxidative stress-related traits, activities of ascorbate peroxidase (APX) and glutathione reductase (GR), and the activities of antioxidant defence system-related enzymes as well as NR activity and endogenous nitric oxide content. EBR reduced leaf Cd2+ content and oxidative stress-related parameters, enhanced plant growth, regulated water relations, and led to further increases in proline content, AsA-GSH cycle-related enzymes' activities, antioxidant defence system-related enzymes as well as NR activity and endogenous nitric oxide content. The EBR and the inhibitor of NR (tungstate) reversed the positive effects of EBR by reducing NO content, showing that NR could be a potential contributor of EBR-induced generation of NO which plays an effective role in tolerance to CdS in pepper plants by accelerating the AsA-GSH cycle and antioxidant enzymes.


Assuntos
Ácido Ascórbico/metabolismo , Brassinosteroides/farmacologia , Cádmio/metabolismo , Glutationa/metabolismo , Nitrato Redutase/metabolismo , Antioxidantes/metabolismo , Cádmio/toxicidade , Capsicum/efeitos dos fármacos , Capsicum/enzimologia , Capsicum/crescimento & desenvolvimento , Capsicum/metabolismo , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Nitrato Redutase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos
8.
Ecotoxicol Environ Saf ; 194: 110338, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32135376

RESUMO

2,2',3,5',6-Pentachlorobiphenyl (PCB95) is known as a persistent pollutant that was found in eggs in China. PCB 95 can be metabolized into OH-PCB95 and MeO-PCB95 in liver microsomes. However, the toxicity and its mechanism of PCB95 or its metabolites have been little studied on laying hens. Herein, chicken embryo liver cells of laying hens were selected and treated with different levels of PCB95 and its two metabolites, and the EC50 of PCB95, OH-PCB95, MeO-PCB95 was 80.85, 4.81 and 107.04 µg/mL respectively, indicating that OH-PCB95 is much more cytotoxic than PCB95 or MeO-PCB95. Targeted metabolomics was further used to study the effects of the parent compound and its metabolites on cell metabolism. The results showed that four primary types of glycerophospholipids were down-regulated after exposure to PCB95 and its metabolites, especially PE and PS (60% more than the control for PCB95, 40% for OH-PCB95, and less than 40% for MeO-PCB95). KEGG pathway analysis based on amino acid metabolism showed that PCB95 may mainly interfere with the amino acids involved in immune regulation (phenylalanine and tyrosine), and OH-PCB95 may be associated with genetic disoders (cysteine, methionine and purine metabolism). However, the metabolic pathways induced by MeO-PCB95 are quite different from those induced by PCB95 and OH-PCB95, affecting mainly D-glutamine and D-glutamate metabolism, alanine and glutamate metabolism, and arginine and proline metabolism; these pathways mainly regulate the elimination of excess purines and are involved in the synthesis of the amino acids required by cells. These results showed that OH-PCB95 has the highest toxicity on chicken embryo liver cells and MeO-PCB95 could be a detoxification product of PCB95 and OH-PCB95. This study contributes to the understanding of the different effects of PCB95 and its metabolites on cellular metabolism, and the data are helpful in evaluating the hepatotoxic effects of these compounds.


Assuntos
Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Aminoácidos/metabolismo , Animais , Embrião de Galinha , Galinhas/metabolismo , China , Ovos , Poluentes Ambientais/metabolismo , Feminino , Hepatócitos/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas , Metabolômica , Metionina/metabolismo , Microssomos Hepáticos/metabolismo , Testes de Toxicidade
9.
Adv Exp Med Biol ; 1219: 1-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130691

RESUMO

The microenvironment depends and generates dependence on all the cells and structures that share the same niche, the biotope. The contemporaneous view of the tumor microenvironment (TME) agrees with this idea. The cells that make up the tumor, whether malignant or not, behave similarly to classes of elements within a living community. These elements inhabit, modify and benefit from all the facilities the microenvironment has to offer and that will contribute to the survival and growth of the tumor and the progression of the disease.The metabolic adaptation to microenvironment is a crucial process conducting to an established tumor able to grow locally, invade and metastasized. The metastatic cancer cells are reasonable more plastic than non-metastatic cancer cells, because the previous ones must survive in the microenvironment where the primary tumor develops and in addition, they must prosper in the microenvironment in the metastasized organ.The metabolic remodeling requires not only the adjustment of metabolic pathways per se but also the readjustment of signaling pathways that will receive and obey to the extracellular instructions, commanding the metabolic adaptation. Many diverse players are pivotal in cancer metabolic fitness from the initial signaling stimuli, going through the activation or repression of genes, until the phenotype display. The new phenotype will permit the import and consumption of organic compounds, useful for energy and biomass production, and the export of metabolic products that are useless or must be secreted for a further recycling or controlled uptake. In the metabolic network, three subsets of players are pivotal: (1) the organic compounds; (2) the transmembrane transporters, and (3) the enzymes.This chapter will present the "Pharaonic" intent of diagraming the interplay between these three elements in an attempt of simplifying and, at the same time, of showing the complex sight of cancer metabolism, addressing the orchestrating role of microenvironment and highlighting the influence of non-cancerous cells.


Assuntos
Neoplasias/metabolismo , Microambiente Tumoral , Progressão da Doença , Humanos , Redes e Vias Metabólicas , Neoplasias/patologia
10.
Bioresour Technol ; 307: 123230, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32222687

RESUMO

Strain Z195 was isolated and identified as Paracoccus denitrificans. Z195 exhibited efficient aerobic denitrification and carbon removal abilities, and removed 93.74% of total nitrogen (TN) and 97.81% of total organic carbon.71.88% of nitrogen was lost as gaseous products.13C-metabolic flux analysis revealed that 95% and 132% of the carbon fluxes entered the Entner-Doudoroff (ED) pathway and tricarboxylic acid (TCA) cycle, respectively. Electrons produced by carbon metabolism markedly promoted the processes of nitrogen metabolism process and aerobic respiration. A response surface methodology model demonstrated that the optimal conditions for the maximum TN removal were a C/N ratio of 7.47, shaking speed of 108 rpm, temperature of 31 °C and initial pH of 8.02. Additionally, the average TN and chemical oxygen demand removal efficiencies of raw wastewater were 89% and 91%, respectively. The results give new insight for understanding metabolic flux analysis of aerobic denitrifying bacteria.


Assuntos
Paracoccus denitrificans , Aerobiose , Bactérias , Desnitrificação , Redes e Vias Metabólicas , Nitratos , Nitrificação , Nitrogênio
13.
World J Microbiol Biotechnol ; 36(3): 49, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157439

RESUMO

Glycerol is a by-product of biodiesel, and it has a great application prospect to be transformed to synthesize high value-added compounds. Pseudomonas chlororaphis GP72 isolated from the green pepper rhizosphere is a plant growth promoting rhizobacteria that can utilize amount of glycerol to synthesize phenazine-1-carboxylic acid (PCA). PCA has been commercially registered as "Shenqinmycin" in China due to its characteristics of preventing pepper blight and rice sheath blight. The aim of this study was to engineer glycerol utilization pathway in P. chlororaphis GP72. First, the two genes glpF and glpK from the glycerol metabolism pathway were overexpressed in GP72ANO separately. Then, the two genes were co-expressed in GP72ANO, improving PCA production from 729.4 mg/L to 993.4 mg/L at 36 h. Moreover, the shunt pathway was blocked to enhance glycerol utilization, resulting in 1493.3 mg/L PCA production. Additionally, we confirmed the inhibition of glpR on glycerol metabolism pathway in P. chlororaphis GP72. This study provides a good example for improving the utilization of glycerol to synthesize high value-added compounds in Pseudomonas.


Assuntos
Glicerol/metabolismo , Engenharia Metabólica/métodos , Pseudomonas chlororaphis/genética , Pseudomonas chlororaphis/metabolismo , Aquaporinas/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Capsicum/microbiologia , China , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Regulação Bacteriana da Expressão Gênica , Técnicas de Inativação de Genes , Glicerolfosfato Desidrogenase/genética , Redes e Vias Metabólicas/genética , Fenazinas/metabolismo , Proteínas Repressoras/genética , Rizosfera
14.
Anticancer Res ; 40(3): 1437-1441, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132040

RESUMO

BACKGROUND/AIM: Polyamines are important for the growth of eukaryotic cells. At high levels, they promote proliferation, invasion and migration of tumour cells. Polyamine metabolism is an important new target for anticancer therapy. Some polyamine analogues can have an inhibitory effect on tumour cells. The aim of this study was to explore the potential of certain butylated derivatives of propanediamine for prostate cancer chemotherapy. MATERIALS AND METHODS: Human prostate cancer cells, LNCaP, were used for the evaluation of the antiproliferative activity of polyamine analogs and their influence on spermine oxidase. RESULTS: Tetrabutyl propanediamine and two new polyamine analogues inhibited the growth of LNCaP cells. At the same time, a strong activation of spermine oxidase was observed. CONCLUSION: The investigated compounds demonstrated their potential value in the therapy of human prostate cancer. Their effect might be attributed to the activation of the polyamine catabolic pathway.


Assuntos
Diaminas/farmacologia , Poliaminas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Poliaminas Biogênicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Redes e Vias Metabólicas , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
15.
Nat Rev Urol ; 17(4): 214-231, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112053

RESUMO

Anabolic metabolism mediated by aberrant growth factor signalling fuels tumour growth and progression. The first biochemical descriptions of the altered metabolic nature of solid tumours were reported by Otto Warburg almost a century ago. Now, the study of tumour metabolism is being redefined by the development of new molecular tools, tumour modelling systems and precise instrumentation together with important advances in genetics, cell biology and spectroscopy. In contrast to Warburg's original hypothesis, accumulating evidence demonstrates a critical role for mitochondrial metabolism and substantial variation in the way in which different tumours metabolize nutrients to generate biomass. Furthermore, computational and experimental approaches suggest a dominant influence of the tissue-of-origin in shaping the metabolic reprogramming that enables tumour growth. For example, the unique metabolic properties of prostate adenocarcinoma are likely to stem from the distinct metabolism of the prostatic epithelium from which it emerges. Normal prostatic epithelium employs comparatively glycolytic metabolism to sustain physiological citrate secretion, whereas prostate adenocarcinoma consumes citrate to power oxidative phosphorylation and fuel lipogenesis, enabling tumour progression through metabolic reprogramming. Current data suggest that the distinct metabolic aberrations in prostate adenocarcinoma are driven by the androgen receptor, providing opportunities for functional metabolic imaging and novel therapeutic interventions that will be complementary to existing diagnostic and treatment options.


Assuntos
Adenocarcinoma/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Proliferação de Células , Ácido Cítrico/metabolismo , Ciclo do Ácido Cítrico , Glicólise , Humanos , Lipogênese , Masculino , Redes e Vias Metabólicas , Fosforilação Oxidativa , Microambiente Tumoral
16.
PLoS One ; 15(3): e0226395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150579

RESUMO

Bacterial microcompartments (MCPs) are protein-based organelles that encapsulate metabolic pathways. Metabolic engineers have recently sought to repurpose MCPs to encapsulate heterologous pathways to increase flux through pathways of interest. As MCP engineering becomes more common, standardized methods for analyzing changes to MCPs and interpreting results across studies will become increasingly important. In this study, we demonstrate that different imaging techniques yield variations in the apparent size of purified MCPs from Salmonella enterica serovar Typhimurium LT2, likely due to variations in sample preparation methods. We provide guidelines for preparing samples for MCP imaging and outline expected variations in apparent size and morphology between methods. With this report we aim to establish an aid for comparing results across studies.


Assuntos
Regulação Bacteriana da Expressão Gênica/fisiologia , Redes e Vias Metabólicas/fisiologia , Salmonella typhimurium/metabolismo , Salmonella typhimurium/genética
17.
RNA ; 26(6): 675-693, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165489

RESUMO

Comparative sequence analyses have been used to discover numerous classes of structured noncoding RNAs, some of which are riboswitches that specifically recognize small-molecule or elemental ion ligands and influence expression of adjacent downstream genes. Determining the correct identity of the ligand for a riboswitch candidate typically is aided by an understanding of the genes under its regulatory control. Riboswitches whose ligands were straightforward to identify have largely been associated with well-characterized metabolic pathways, such as coenzyme or amino acid biosynthesis. Riboswitch candidates whose ligands resist identification, collectively known as orphan riboswitches, are often associated with genes coding for proteins of unknown function, or genes for various proteins with no established link to one another. The cognate ligands for 16 former orphan riboswitch motifs have been identified to date. The successful pursuit of the ligands for these classes has provided insight into areas of biology that are not yet fully explored, such as ion homeostasis, signaling networks, and other previously underappreciated biochemical or physiological processes. Herein we discuss the strategies and methods used to match ligands with orphan riboswitch classes, and overview the lessons learned to inform and motivate ongoing efforts to identify ligands for the many remaining candidates.


Assuntos
Regulação Bacteriana da Expressão Gênica , Riboswitch , Bactérias/genética , Bactérias/metabolismo , Ligantes , Redes e Vias Metabólicas/genética , Motivos de Nucleotídeos , Transdução de Sinais
18.
Nat Commun ; 11(1): 1190, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132540

RESUMO

Genes in plant secondary metabolic pathways enable biosynthesis of a range of medically and industrially important compounds, and are often clustered on chromosomes. Here, we study genomic clustering in the benzylisoquinoline alkaloid (BIA) pathway in opium poppy (Papaver somniferum), exploring relationships between gene expression, copy number variation, and metabolite production. We use Hi-C to improve the existing draft genome assembly, yielding chromosome-scale scaffolds that include 35 previously unanchored BIA genes. We find that co-expression of BIA genes increases within clusters and identify candidates with unknown function based on clustering and covariation in expression and alkaloid production. Copy number variation in critical BIA genes correlates with stark differences in alkaloid production, linking noscapine production with an 11-gene deletion, and increased thebaine/decreased morphine production with deletion of a T6ODM cluster. Our results show that the opium poppy genome is still dynamically evolving in ways that contribute to medically and industrially important phenotypes.


Assuntos
Benzilisoquinolinas/metabolismo , Variações do Número de Cópias de DNA , Família Multigênica , Papaver/genética , Metabolismo Secundário/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genoma de Planta/genética , Genômica , Redes e Vias Metabólicas/genética , Papaver/metabolismo
19.
PLoS Biol ; 18(3): e3000681, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32196485

RESUMO

The interplay between nutrition and the microbial communities colonizing the gastrointestinal tract (i.e., gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how host-associated bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobiotic Drosophila melanogaster larvae independently associated with Acetobacter pomorumWJL (ApWJL) and Lactobacillus plantarumNC8 (LpNC8), 2 model Drosophila-associated bacteria, we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities of Drosophila germ-free (GF) larvae and its 2 bacterial partners. We first established that ApWJL and LpNC8 differentially fulfill the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients, and trace metals. We found that Drosophila-associated bacteria not only fortify the host's diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating, and delivering contaminant traces of micronutrients. Our systematic work reveals that beyond the molecular dialogue engaged between the host and its bacterial partners, Drosophila and its associated bacteria establish an integrated nutritional network relying on nutrient provision and utilization.


Assuntos
Acetobacter/fisiologia , Drosophila melanogaster/microbiologia , Drosophila melanogaster/fisiologia , Lactobacillus/fisiologia , Necessidades Nutricionais/fisiologia , Acetobacter/genética , Acetobacter/metabolismo , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Lactobacillus/genética , Lactobacillus/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , Larva/microbiologia , Larva/fisiologia , Redes e Vias Metabólicas , Micronutrientes/metabolismo , Especificidade da Espécie
20.
Adv Immunol ; 145: 129-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32081196

RESUMO

Immune responses are often accompanied by radical changes of cellular metabolism of immune cells. On the other hand, an ever increasing number of metabolic pathways and products have been found to possess immune regulatory functions. The field of immunometabolism that investigates the interplay between metabolism and immunity has developed rapidly during the past decade. In this chapter, we attempt to summarize the recent progresses by scientists in China on metabolic regulation of innate immunity from the following three perspectives: metabolic regulation of myeloid cell functions, metabolic adaptations of tissue resident myeloid cells, and metabolism and immunity at the mucosal surfaces.


Assuntos
Metabolismo Energético/imunologia , Imunidade Inata , Redes e Vias Metabólicas/imunologia , Células Mieloides/imunologia , Tecido Adiposo/citologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Metabolismo Energético/genética , Fígado Gorduroso/imunologia , Fígado Gorduroso/metabolismo , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Macrófagos do Fígado/imunologia , Macrófagos do Fígado/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Redes e Vias Metabólicas/genética , Células Mieloides/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
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