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1.
Pharmacol Ther ; 256: 108615, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382882

RESUMO

Owing to renal reabsorption and the loss of uricase activity, uric acid (UA) is strictly maintained at a higher physiological level in humans than in other mammals, which provides a survival advantage during evolution but increases susceptibility to certain diseases such as gout. Although monosodium urate (MSU) crystal precipitation has been detected in different tissues of patients as a trigger for disease, the pathological role of soluble UA remains controversial due to the lack of causality in the clinical setting. Abnormal elevation or reduction of UA levels has been linked to some of pathological status, also known as U-shaped association, implying that the physiological levels of UA regulated by multiple enzymes and transporters are crucial for the maintenance of health. In addition, the protective potential of UA has also been proposed in aging and some diseases. Therefore, the role of UA as a double-edged sword in humans is determined by its physiological or non-physiological levels. In this review, we summarize biosynthesis, membrane transport, and physiological functions of UA. Then, we discuss the pathological involvement of hyperuricemia and hypouricemia as well as the underlying mechanisms by which UA at abnormal levels regulates the onset and progression of diseases. Finally, pharmacological strategies for urate-lowering therapy (ULT) are introduced, and current challenges in UA study and future perspectives are also described.


Assuntos
Hiperuricemia , Ácido Úrico , Animais , Humanos , Ácido Úrico/uso terapêutico , Hiperuricemia/tratamento farmacológico , Mamíferos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38381637

RESUMO

Salient object ranking (SOR) aims to segment salient objects in an image and simultaneously predict their saliency rankings, according to the shifted human attention over different objects. The existing SOR approaches mainly focus on object-based attention, e.g., the semantic and appearance of object. However, we find that the scene context plays a vital role in SOR, in which the saliency ranking of the same object varies a lot at different scenes. In this paper, we thus make the first attempt towards explicitly learning scene context for SOR. Specifically, we establish a large-scale SOR dataset of 24,373 images with rich context annotations, i.e., scene graphs, segmentation, and saliency rankings. Inspired by the data analysis on our dataset, we propose a novel graph hypernetwork, named HyperSOR, for context-aware SOR. In HyperSOR, an initial graph module is developed to segment objects and construct an initial graph by considering both geometry and semantic information. Then, a scene graph generation module with multi-path graph attention mechanism is designed to learn semantic relationships among objects based on the initial graph. Finally, a saliency ranking prediction module dynamically adopts the learned scene context through a novel graph hypernetwork, for inferring the saliency rankings. Experimental results show that our HyperSOR can significantly improve the performance of SOR.

3.
Langmuir ; 40(1): 960-967, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38150588

RESUMO

Surfactant-free microemulsions (SFMEs) have been explored extensively to avoid the residual surfactant problem caused by traditional surfactant microemulsions. Many researchers focused on the SFMEs with tertiary amine, which exhibited the typical CO2 response behavior. In this study, the phase diagram of the SFMEs consisting of tripropylamine (TPA), ethanol, and water was readily prepared via the measurements of electrical conductivity. The CO2 response behavior of SFME was confirmed by determination of conductivity and measurement of the average diameter of SFME, which was mainly dependent on the protonation of TPA induced by the additional CO2. The transition of protonated TPA to a more hydrophilic nature from lipophilicity to hydrophilicity should be responsible for the variation of SFME average diameter. In addition, the SFMEs exhibited remarkable solubilizing capacity of crude oil, and three types of SFMEs achieved more than 80% oil removal rate in the washing process of oil sands. It was noted that both oil-in-water and bicontinuous SFMEs could be circularly utilized at least three times with a relatively high oil removal rate (%). Our work provided the insight perspective on the mechanism of SFMEs with a CO2 response behavior.

4.
Materials (Basel) ; 15(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36363441

RESUMO

This study focuses on the effect of the substrate temperature (TS) on the quality of VO2 thin films prepared by DC magnetron sputtering. TS was varied from 350 to 600 °C and the effects on the surface morphology, microstructure, optical and electrical properties of the films were investigated. The results show that TS below 500 °C favors the growth of V2O5 phase, whereas higher TS (≥500 °C) facilitates the formation of the VO2 phase. Optical characterization of the as-prepared VO2 films displayed a reduced optical transmittance (T˜) across the near-infrared region (NIR), reduced phase transition temperature (Tt), and broadened hysteresis width (ΔH) through the phase transition region. In addition, a decline of the luminous modulation (ΔT˜lum) and solar modulation (ΔT˜sol) efficiencies of the as-prepared films have been determined. Furthermore, compared with the high-quality films reported previously, the electrical conductivity (σ) as a function of temperature (T) reveals reduced conductivity contrast (Δσ) between the insulating and metallic phases of the VO2 films, which was of the order of 2. These outcomes indicated the presence of defects and unrelaxed lattice strain in the films. Further, the comparison of present results with those in the literature from similar works show that the preparation of high-quality films at TS lower than 650 °C presents significant challenges.

5.
Biochem Biophys Res Commun ; 581: 6-11, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34637964

RESUMO

Cluster of differentiation (CD) 38, a major enzyme for nicotinamide adenine dinucleotide (NAD+) degradation, plays a key role in inflammation. Meanwhile, intracellular NAD+ decline is also associated with inflammatory responses. However, whether CD38 activation is involved in gouty inflammation has not been elucidated. The present study aimed to clarify the role of CD38 in monosodium urate crystals (MSU)-triggered inflammatory responses. The results showed that MSU crystals increased the protein expression of CD38 in time- and concentration-dependent manner in THP-1 macrophages and mouse bone marrow-derived macrophages (BMDMs). Moreover, intracellular NAD+ levels were reduced by MSU crystals along with the increased IL-1ß release. However, CD38 inhibition by 78c elevated intracellular NAD+ levels and suppressed IL-1ß release in MSU crystals-treated THP-1 macrophages and BMDMs. Interestingly, CD38 inhibition without significant elevation of intracellular NAD+ also decreased IL-1ß release driven by MSU crystals in THP-1 macrophages. In conclusion, the present study revealed that MSU crystals could activate CD38 with the ensuing intracellular NAD+ decline to promote inflammatory responses in THP-1 macrophages and BMDMs, while CD38 inhibition could suppress MSU crystals-triggered inflammatory responses, indicating that CD38 is a potential therapeutic target for gout.


Assuntos
ADP-Ribosil Ciclase 1/genética , Interleucina-1beta/genética , Macrófagos/efeitos dos fármacos , Glicoproteínas de Membrana/genética , Ácido Úrico/farmacologia , ADP-Ribosil Ciclase 1/agonistas , ADP-Ribosil Ciclase 1/metabolismo , Animais , Cristalização , Feminino , Regulação da Expressão Gênica , Gota/etiologia , Gota/genética , Gota/metabolismo , Gota/patologia , Humanos , Hiperuricemia/etiologia , Hiperuricemia/genética , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Inflamação , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Glicoproteínas de Membrana/agonistas , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , NAD/metabolismo , Cultura Primária de Células , Transdução de Sinais , Células THP-1
6.
Langmuir ; 37(33): 10061-10070, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34392688

RESUMO

Colloidal stability of modified graphene oxide (GO) is fundamental for its practical applications. Meanwhile, most of the investigations mainly focused on the nanosheets modified by a certain amount of modifiers and neglected the effects of the modification degree, which could vary the physical and chemical properties of modified GO and significantly affect its stability in solution. To the best of our knowledge, this study initially investigated the impact of modification degrees on the colloidal stability of graphene-based amphiphilic Janus nanosheets (JGO) via both experimental and theoretical approaches. The prepared JGO, asymmetrically grafted by dodecylamine, exhibited a direct relation between the modification degree and nanosheet thickness, refractive index, electrostatic properties, hydrophobicity, and the ultimate colloidal stability. In addition, the ionic strength imposed distinctive influences on the aggregation behavior of JGO. Based on the comparison between experimental results and theoretical calculation, it was revealed that the JGO should be modeled as two-dimensional (2D) nanosheets in pure water and be treated as 3D spherical particles in electrolyte solutions for the prediction with the extended Derjaguin-Landau-Verwey-Overbeek theory.

7.
Curr Pharm Biotechnol ; 22(5): 609-621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33198615

RESUMO

BACKGROUND: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. OBJECTIVE: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. METHODS: The Osteoprotegerin (OPG)/Receptor Activator of NF-κB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. RESULT: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. CONCLUSION: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.


Assuntos
Proteína Forkhead Box O1/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/efeitos dos fármacos , Fosfocreatina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Células 3T3 , Fosfatase Alcalina/biossíntese , Fosfatase Alcalina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos dos fármacos , Camundongos , Osteoprotegerina/efeitos dos fármacos , Osteoprotegerina/metabolismo , Estresse Oxidativo , Ligante RANK/efeitos dos fármacos , Ligante RANK/metabolismo , Espécies Reativas de Oxigênio
9.
BMC Genomics ; 20(1): 799, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675924

RESUMO

BACKGROUND: Microsatellites, or simple sequence repeats (SSRs), represent important DNA variations that are widely distributed across the entire plant genome and can be used to develop SSR markers, which can then be used to conduct genetic analyses and molecular breeding. Cultivated peanut (A. hypogaea L.), an important oil crop worldwide, is an allotetraploid (AABB, 2n = 4× = 40) plant species. Because of its complex genome, genomic marker development has been very challenging. However, sequencing of cultivated peanut genome allowed us to develop genomic markers and construct a high-density physical map. RESULTS: A total of 8,329,496 SSRs were identified, including 3,772,653, 4,414,961, and 141,882 SSRs that were distributed in subgenome A, B, and nine scaffolds, respectively. Based on the flanking sequences of the identified SSRs, a total of 973,984 newly developed SSR markers were developed in subgenome A (462,267), B (489,394), and nine scaffolds (22,323), with an average density of 392.45 markers per Mb. In silico PCR evaluation showed that an average of 88.32% of the SSR markers generated only one in silico-specific product in two tetraploid A. hypogaea varieties, Tifrunner and Shitouqi. A total of 39,599 common SSR markers were identified among the two A. hypogaea varieties and two progenitors, A. duranensis and A. ipaensis. Additionally, an amplification effectiveness of 44.15% was observed by real PCR validation. Moreover, a total of 1276 public SSR loci were integrated with the newly developed SSR markers. Finally, a previously known leaf spot quantitative trait locus (QTL), qLLS_T13_A05_7, was determined to be in a 1.448-Mb region on chromosome A05. In this region, a total of 819 newly developed SSR markers were located and 108 candidate genes were detected. CONCLUSIONS: The availability of these newly developed and public SSR markers both provide a large number of molecular markers that could potentially be used to enhance the process of trait genetic analyses and improve molecular breeding strategies for cultivated peanut.


Assuntos
Arachis/genética , Genômica , Repetições de Microssatélites/genética , Simulação por Computador , Genoma de Planta/genética
10.
Materials (Basel) ; 12(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284405

RESUMO

In this work, VO2 thin films were deposited on Si wafers (onto (100) surface) by DC magnetron sputtering under different cathode bias voltages. The effects of substrate biasing on the structural and optical properties were investigated. The results show that the metal-insulator transition (MIT) temperature of VO2 thin films can be increased up to 14 K by applying a cathode bias voltage, compared to deposition conditions without any bias. The decrease in the transition efficiency and increase in the transition temperature are attributed to the enlarged grain size, increased defects, and the residual stress in the VO2 thin films induced by biasing. The optical transmittance measurements for different thickness films indicate an attenuation coefficient of 3.1 × 107 m-1 at 2000 nm or an extinction coefficient of 4.9 in the metal phase. The optical transmittance vs wavelength characteristics point to an indirect bandgap of 0.6 ± 0.5 eV and significant scattering in the bulk and/or at the interface.

11.
Mol Plant ; 12(7): 920-934, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30902685

RESUMO

Cultivated peanut (Arachis hypogaea) is an allotetraploid crop planted in Asia, Africa, and America for edible oil and protein. To explore the origins and consequences of tetraploidy, we sequenced the allotetraploid A. hypogaea genome and compared it with the related diploid Arachis duranensis and Arachis ipaensis genomes. We annotated 39 888 A-subgenome genes and 41 526 B-subgenome genes in allotetraploid peanut. The A. hypogaea subgenomes have evolved asymmetrically, with the B subgenome resembling the ancestral state and the A subgenome undergoing more gene disruption, loss, conversion, and transposable element proliferation, and having reduced gene expression during seed development despite lacking genome-wide expression dominance. Genomic and transcriptomic analyses identified more than 2 500 oil metabolism-related genes and revealed that most of them show altered expression early in seed development while their expression ceases during desiccation, presenting a comprehensive map of peanut lipid biosynthesis. The availability of these genomic resources will facilitate a better understanding of the complex genome architecture, agronomically and economically important genes, and genetic improvement of peanut.


Assuntos
Arachis , Metabolismo dos Lipídeos/genética , Óleo de Amendoim/metabolismo , Arachis/genética , Genoma de Planta , Filogenia , Análise de Sequência de DNA , Transcriptoma/genética , Sequenciamento Completo do Genoma
12.
Asian J Pharm Sci ; 14(6): 677-686, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32104494

RESUMO

To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam, renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats. A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions. Renal slices were taken to examine the uptake of piperacillin and tazobactam. Pharmacokinetic studies of ß-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam on ß-lactamase. The AUC (from 2.93 ±â€¯0.58 to 6.52 ±â€¯1.44 mg·min/ml) and the plasma clearance (CLP ) (from 2.41 ±â€¯1.20 to 0.961 ±â€¯0.212 ml/min/kg) of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats. The renal clearance (CLR ) of tazobactam decreased from 1.30 ±â€¯0.50 to 0.361 ±â€¯0.043 ml/min/kg. In summary, there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3. Piperacillin enhances the inhibitory effect of tazobactam on ß-lactamase through the inhibition of rOat1 and rOat3 in rats. The contribution rate of rOat1/3 for the synergistic effect was 20% when the two drugs were coadministered.

13.
BMC Genomics ; 19(1): 887, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30526476

RESUMO

BACKGROUND: Many large-effect quantitative trait loci (QTLs) for yield and disease resistance related traits have been identified in different mapping populations of peanut (Arachis hypogaea L.) under multiple environments. However, only a limited number of QTLs have been used in marker-assisted selection (MAS) because of unfavorable epistatic interactions between QTLs in different genetic backgrounds. Thus, it is essential to identify consensus QTLs across different environments and genetic backgrounds for use in MAS. Here, we used QTL meta-analysis to identify a set of consensus QTLs for yield and disease resistance related traits in peanut. RESULTS: A new integrated consensus genetic map with 5874 loci was constructed. The map comprised 20 linkage groups (LGs) and was up to a total length of 2918.62 cM with average marker density of 2.01 loci per centimorgan (cM). A total of 292 initial QTLs were projected on the new consensus map, and 40 meta-QTLs (MQTLs) for yield and disease resistance related traits were detected on four LGs. The genetic intervals of these consensus MQTLs varied from 0.20 cM to 7.4 cM, which is narrower than the genetic intervals of the initial QTLs, meaning they may be suitable for use in MAS. Importantly, a region of the map that previously co-localized multiple major QTLs for pod traits was narrowed from 3.7 cM to 0.7 cM using an overlap region of four MQTLs for yield related traits on LG A05, which corresponds to a physical region of about 630.3 kb on the A05 pseudomolecule of peanut, including 38 annotated candidate genes (54 transcripts) related to catalytic activity and metabolic process. Additionally, one major MQTL for late leaf spot (LLS) was identified in a region of about 0.38 cM. BLAST searches identified 26 candidate genes (30 different transcripts) in this region, some of which were annotated as related to regulation of disease resistance in different plant species. CONCLUSIONS: Combined with the high-density marker consensus map, all the detected MQTLs could be useful in MAS. The biological functions of the 64 candidate genes should be validated to unravel the molecular mechanisms of yield and disease resistance in peanut.


Assuntos
Arachis/genética , Mapeamento Cromossômico/métodos , Sequência Consenso/genética , Resistência à Doença/genética , Ligação Genética , Doenças das Plantas/genética , Locos de Características Quantitativas/genética , Característica Quantitativa Herdável , Estudos de Associação Genética
15.
Toxicol Lett ; 295: 195-204, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29964132

RESUMO

The present study aimed to investigate the regulation of JBP485 on the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp), which can accelerate the renal excretion of accumulated endogenous toxins to attenuate vancomycin-induced nephrotoxicity (VIN) in rats. Vancomycin suppressed the mRNA and protein expressions of Oat1, Oat3, Oct2, Mrp2 and P-gp to reduce the renal excretion of endogenous toxins (e.g. indoxyl sulfate). However, JBP485 could reverse these effects and improved the pathological condition and morphology of rat kidney with a decrease in wet weight. Moreover, JBP485 decreased the number of apoptosis cells in TUNEL staining as well as reversed the decreased expression of B-cell lymphoma-2 (Bcl-2) and the increased expressions of Bcl-2-like protein 4 (Bax) and Caspase-3 in rat kidney. In addition, JBP485 also increased the level of superoxide dismutase (SOD) and decreased the level of malondialdehyde (MDA) in rat kidney. But JBP485 did not affect the plasma concentrations of vancomycin. In conclusion, the mechanism of VIN might be involved in, at least in part, suppressing the expressions of Oat1, Oat3, Oct2, Mrp2 and P-gp, and JBP485 could attenuate VIN in rats.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Transportador 2 de Cátion Orgânico/metabolismo , Peptídeos Cíclicos/farmacologia , Vancomicina , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Citoproteção , Modelos Animais de Doenças , Regulação da Expressão Gênica , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Proteína 1 Transportadora de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Transportador 2 de Cátion Orgânico/genética , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Eliminação Renal/efeitos dos fármacos
16.
Front Plant Sci ; 9: 604, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29774047

RESUMO

Peanut (Arachis hypogaea L.), an important leguminous crop, is widely cultivated in tropical and subtropical regions. Peanut is an allotetraploid, having A and B subgenomes that maybe have originated in its diploid progenitors Arachis duranensis (A-genome) and Arachis ipaensis (B-genome), respectively. We previously sequenced the former and here present the draft genome of the latter, expanding our knowledge of the unique biology of Arachis. The assembled genome of A. ipaensis is ~1.39 Gb with 39,704 predicted protein-encoding genes. A gene family analysis revealed that the FAR1 family may be involved in regulating peanut special fruit development. Genomic evolutionary analyses estimated that the two progenitors diverged ~3.3 million years ago and suggested that A. ipaensis experienced a whole-genome duplication event after the divergence of Glycine max. We identified a set of disease resistance-related genes and candidate genes for biological nitrogen fixation. In particular, two and four homologous genes that may be involved in the regulation of nodule development were obtained from A. ipaensis and A. duranensis, respectively. We outline a comprehensive network involved in drought adaptation. Additionally, we analyzed the metabolic pathways involved in oil biosynthesis and found genes related to fatty acid and triacylglycerol synthesis. Importantly, three new FAD2 homologous genes were identified from A. ipaensis and one was completely homologous at the amino acid level with FAD2 from A. hypogaea. The availability of the A. ipaensis and A. duranensis genomic assemblies will advance our knowledge of the peanut genome.

17.
Plant Mol Biol ; 97(1-2): 177-185, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29700675

RESUMO

KEY MESSAGE: A first creation of high oleic acid peanut varieties by using transcription activator-like effecter nucleases (TALENs) mediated targeted mutagenesis of Fatty Acid Desaturase 2 (FAD2). Transcription activator like effector nucleases (TALENs), which allow the precise editing of DNA, have already been developed and applied for genome engineering in diverse organisms. However, they are scarcely used in higher plant study and crop improvement, especially in allopolyploid plants. In the present study, we aimed to create targeted mutagenesis by TALENs in peanut. Targeted mutations in the conserved coding sequence of Arachis hypogaea fatty acid desaturase 2 (AhFAD2) were created by TALENs. Genetic stability of AhFAD2 mutations was identified by DNA sequencing in up to 9.52 and 4.11% of the regeneration plants at two different targeted sites, respectively. Mutation frequencies among AhFAD2 mutant lines were significantly correlated to oleic acid accumulation. Genetically, stable individuals of positive mutant lines displayed a 0.5-2 fold increase in the oleic acid content compared with non-transgenic controls. This finding suggested that TALEN-mediated targeted mutagenesis could increase the oleic acid content in edible peanut oil. Furthermore, this was the first report on peanut genome editing event, and the obtained high oleic mutants could serve for peanut breeding project.


Assuntos
Arachis/metabolismo , Ácidos Graxos Dessaturases/genética , Ácido Oleico/metabolismo , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Arachis/genética , Ácidos Graxos Dessaturases/metabolismo , Mutagênese , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Ligação Proteica , Sementes/metabolismo
18.
Int J Pharm ; 537(1-2): 172-182, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29277663

RESUMO

This study aimed to demonstrate that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between piperacillin and tazobactam. After co-administration with piperacillin in rats, the AUC of tazobactam in plasma was significantly increased, and t1/2ß was prolonged with significant reduction in plasma clearance, renal clearance and cumulative urinary excretion. In rat and human kidney slices, probenecid, p-aminohippurate and benzylpenicillin inhibited the uptake of piperacillin and tazobactam. Piperacillin significantly inhibited the uptake of tazobactam. Moreover, the uptakes of piperacillin, tazobactam and sulbactam in hOAT1/3-HEK293 cells were significantly higher compared with mock-HEK293 cells, respectively. Piperacillin significantly inhibited the uptake of tazobactam in hOAT1/3-HEK293 cells. The Km values of tazobactam (431 ±â€¯67 µM for hOAT1, 377 ±â€¯63 µM for hOAT3) were significantly higher than those of piperacillin (37 ±â€¯5 µM for hOAT1, 172 ±â€¯28 µM for hOAT3). This suggested that piperacillin has a stronger affinity to hOAT1/3 than tazobactam. Meanwhile, the Km values of tazobactam were increased in the presence of piperacillin with unchanged Vmax. This indicated that piperacillin inhibited the uptake of tazobactam in a competitive manner. In conclusion, piperacillin and tazobactam are the substrates of hOAT1/3, and OAT1/3 mediate the DDI between piperacillin and tazobactam.


Assuntos
Interações Medicamentosas/fisiologia , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Ácido Penicilânico/análogos & derivados , Piperacilina/farmacologia , Animais , Linhagem Celular , Células HEK293 , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Ácido Penicilânico/farmacologia , Penicilina G/metabolismo , Probenecid/metabolismo , Ratos , Ratos Wistar , Sulbactam/farmacologia , Tazobactam , Ácido p-Aminoipúrico/metabolismo
19.
Proc Natl Acad Sci U S A ; 113(24): 6785-90, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27247390

RESUMO

Peanut or groundnut (Arachis hypogaea L.), a legume of South American origin, has high seed oil content (45-56%) and is a staple crop in semiarid tropical and subtropical regions, partially because of drought tolerance conferred by its geocarpic reproductive strategy. We present a draft genome of the peanut A-genome progenitor, Arachis duranensis, and 50,324 protein-coding gene models. Patterns of gene duplication suggest the peanut lineage has been affected by at least three polyploidizations since the origin of eudicots. Resequencing of synthetic Arachis tetraploids reveals extensive gene conversion in only three seed-to-seed generations since their formation by human hands, indicating that this process begins virtually immediately following polyploid formation. Expansion of some specific gene families suggests roles in the unusual subterranean fructification of Arachis For example, the S1Fa-like transcription factor family has 126 Arachis members, in contrast to no more than five members in other examined plant species, and is more highly expressed in roots and etiolated seedlings than green leaves. The A. duranensis genome provides a major source of candidate genes for fructification, oil biosynthesis, and allergens, expanding knowledge of understudied areas of plant biology and human health impacts of plants, informing peanut genetic improvement and aiding deeper sequencing of Arachis diversity.


Assuntos
Arachis , Genoma de Planta/fisiologia , Família Multigênica/fisiologia , Óleos de Plantas/metabolismo , Proteínas de Plantas , Tetraploidia , Arachis/genética , Arachis/metabolismo , Humanos , Óleo de Amendoim , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
20.
Plant Biotechnol J ; 14(5): 1215-24, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26502832

RESUMO

A characteristic feature of peanut is the subterranean fructification, geocarpy, in which the gynophore ('peg'), a specialized organ that transitions from upward growth habit to downward outgrowth upon fertilization, drives the developing pod into the soil for subsequent development underground. As a step towards understanding this phenomenon, we explore the developmental dynamics of the peanut pod transcriptome at 11 successive stages. We identified 110 217 transcripts across developmental stages and quantified their abundance along a pod developmental gradient in pod wall. We found that the majority of transcripts were differentially expressed along the developmental gradient as well as identified temporal programs of gene expression, including hundreds of transcription factors. Thought to be an adaptation to particularly harsh subterranean environments, both up- and down-regulated gene sets in pod wall were enriched for response to a broad array of stimuli, like gravity, light and subterranean environmental factors. We also identified hundreds of transcripts associated with gravitropism and photomorphogenesis, which may be involved in the geocarpy. Collectively, this study forms a transcriptional baseline for geocarpy in peanut as well as provides a considerable body of evidence that transcriptional regulation in peanut aerial and subterranean fruits is complex.


Assuntos
Arachis/genética , Regulação da Expressão Gênica de Plantas , Gravitropismo/genética , Transcriptoma , Arachis/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Ontologia Genética , Proteínas de Plantas/genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Análise de Sequência de RNA
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