Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
New Phytol ; 242(5): 1996-2010, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38571393

RESUMO

The conquest of land by plants was concomitant with, and possibly enabled by, the evolution of three-dimensional (3D) growth. The moss Physcomitrium patens provides a model system for elucidating molecular mechanisms in the initiation of 3D growth. Here, we investigate whether the phytohormone ethylene, which is believed to have been a signal before land plant emergence, plays a role in 3D growth regulation in P. patens. We report ethylene controls 3D gametophore formation, based on results from exogenously applied ethylene and genetic manipulation of PpEIN2, which is a central component in the ethylene signaling pathway. Overexpression (OE) of PpEIN2 activates ethylene responses and leads to earlier formation of gametophores with fewer gametophores produced thereafter, phenocopying ethylene-treated wild-type. Conversely, Ppein2 knockout mutants, which are ethylene insensitive, show initially delayed gametophore formation with more gametophores produced later. Furthermore, pharmacological and biochemical analyses reveal auxin levels are decreased in the OE lines but increased in the knockout mutants. Our results suggest that evolutionarily, ethylene and auxin molecular networks were recruited to build the plant body plan in ancestral land plants. This might have played a role in enabling ancient plants to acclimate to the continental surfaces of the planet.


Assuntos
Bryopsida , Etilenos , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Proteínas de Plantas , Etilenos/metabolismo , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacologia , Bryopsida/crescimento & desenvolvimento , Bryopsida/genética , Bryopsida/efeitos dos fármacos , Bryopsida/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Células Germinativas Vegetais/metabolismo , Células Germinativas Vegetais/crescimento & desenvolvimento , Células Germinativas Vegetais/efeitos dos fármacos , Mutação/genética
2.
Eur J Neurol ; 31(3): e16167, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38009830

RESUMO

BACKGROUND AND PURPOSE: Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory-like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD. METHODS: The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity. RESULTS: A 20-s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5-12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn-Yahr stage. CONCLUSIONS: This study provides a fast, low-cost and non-invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/patologia , Inteligência Artificial , Aprendizado de Máquina
3.
Science ; 382(6670): 579-584, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37917705

RESUMO

Global land water underpins livelihoods, socioeconomic development, and ecosystems. It remains unclear how water availability has changed in recent decades. Using an ensemble of observations, we quantified global land water availability over the past two decades. We show that the Southern Hemisphere has dominated the declining trend in global water availability from 2001 to 2020. The significant decrease occurs mainly in South America, southwestern Africa, and northwestern Australia. In the Northern Hemisphere, the complex regional increasing and decreasing trends cancel each other, resulting in a negligible hemispheric trend. The variability and trend in water availability in the Southern Hemisphere are largely driven by precipitation associated with climate modes, particularly the El Niño-Southern Oscillation. This study highlights their dominant role in controlling global water availability.

4.
Entropy (Basel) ; 25(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37998242

RESUMO

Fault diagnosis of rotating machinery plays an important role in modern industrial machines. In this paper, a modified sparse Bayesian classification model (i.e., Standard_SBC) is utilized to construct the fault diagnosis system of rotating machinery. The features are extracted and adopted as the input of the SBC-based fault diagnosis system, and the kernel neighborhood preserving embedding (KNPE) is proposed to fuse the features. The effectiveness of the fault diagnosis system of rotating machinery based on KNPE and Standard_SBC is validated by utilizing two case studies: rolling bearing fault diagnosis and rotating shaft fault diagnosis. Experimental results show that base on the proposed KNPE, the feature fusion method shows superior performance. The accuracy of case1 and case2 is improved from 93.96% to 99.92% and 98.67% to 99.64%, respectively. To further prove the superiority of the KNPE feature fusion method, the kernel principal component analysis (KPCA) and relevance vector machine (RVM) are utilized, respectively. This study lays the foundation for the feature fusion and fault diagnosis of rotating machinery.

5.
Plant Signal Behav ; 17(1): 2145057, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36403161

RESUMO

Plant glutamate receptor homologs (GLRs), which function as key calcium channels, play pivotal roles in various developmental processes as well as stress responses. The moss Physcomitrium patens, a representative of the earliest land plant lineage, possess multiple pathways of hormone signaling for coordinating growth and adaptation responses. However, it is not clear whether GLRs are connected to hormone-mediated growth control in the moss. In this study, we report that one of the two GLRs in P. patens, PpGLR1, involves in abscisic acid (ABA)-mediated growth regulation. ABA represses the growth of wild-type moss, and intriguingly, the PpGLR1 transcript levels are significantly increased in response to ABA treatment, based on both gene expression and the PpGLR1pro::GUS reporter results. Furthermore, the growth of Ppglr1 knockout moss mutants is hypersensitive to ABA treatment. These results suggest that PpGLR1 plays a critical role in ABA-mediated growth regulation, which provide useful information for our further investigation of the regulatory mechanism between Ca2+ signal and ABA in moss growth control.


Assuntos
Ácido Abscísico , Bryopsida , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Bryopsida/genética , Bryopsida/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo , Hormônios/metabolismo
6.
Entropy (Basel) ; 24(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35741533

RESUMO

(1) Background: A typical cardiac cycle consists of a P-wave, a QRS complex, and a T-wave, and these waves are perfectly shown in electrocardiogram signals (ECG). When atrial fibrillation (AF) occurs, P-waves disappear, and F-waves emerge. F-waves contain information on the cause of atrial fibrillation. Therefore it is essential to extract F-waves from the ECG signal. However, F-waves overlap the QRS complex and T-waves in both the time and frequency domain, causing this matter to be a difficult one. (2) Methods: This paper presents an optimized resonance-based signal decomposition method for detecting F-waves in single-lead ECG signals with atrial fibrillation (AF). It represents the ECG signal utilizing morphological component analysis as a linear combination of a finite number of components selected from the high-resonance and low-resonance dictionaries, respectively. The linear combination of components in the low-resonance dictionary reconstructs the oscillatory part (F-wave) of the ECG signal. In contrast, the linear combination of components in the high-resonance dictionary reconstructs the transient components part (QRST wave). The tunable Q-factor wavelet transform generates the high and low resonance dictionaries, with a high Q-factor producing a high resonance dictionary and a low Q-factor producing a low resonance dictionary. The different Q-factor settings affect the dictionaries' characteristics, hence the F-wave extraction. A genetic algorithm was used to optimize the Q-factor selection to select the optimal Q-factor. (3) Results: The presented method helps reduce RMSE between the extracted and the simulated F-waves compared to average beat subtraction (ABS) and principal component analysis (PCA). According to the amplitude of the F-wave, RMSE is reduced by 0.24-0.32. Moreover, the dominant frequency of F-waves extracted by the presented method is clearer and more resistant to interference. The presented method outperforms the other two methods, ABS and PCA, in F-wave extraction from AF-ECG signals with the ventricular premature heartbeat. (4) Conclusion: The proposed method can potentially improve the accuracy of F-wave extraction for mobile ECG monitoring equipment, especially those with fewer leads.

7.
Sci Total Environ ; 836: 155715, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35525365

RESUMO

Based on in vitro and in silico assays as well as proteome analysis, this study explored the nongenomic mechanism for butyl benzyl phthalate (BBP)-induced thyroid disruption. Molecular docking simulations showed that BBP could dock into the Arg-Gly-Asp (RGD) domain of integrin αvß3 and form hydrogen bonds with a docking energy of -35.80 kcal/mol. This chemical enhanced rat pituitary tumor cell (GH3) proliferation and exhibited thyroid hormone-disrupting effects at 5-10 µmol/L. Meanwhile, BBP upregulated ß3 gene expression and activated the downstream mitogen-activated protein kinase (MAPK) pathway in GH3 cells. Interestingly, GH3 cell proliferation was attenuated by integrin αvß3 inhibitor (RGD peptide) or ERK1/2 inhibitor (PD98059), suggesting that the disruptions might be partly attributed to its interaction with integrin αvß3 and activation of MAPK. Furthermore, quantitative proteomic analysis of zebrafish embryos exposed to BBP at an environmentally relevant concentration of 0.3 µmol/L revealed that BBP perturbed proteins and pathways related to cell communication (e.g., integrin binding) and signal transduction (e.g., MAPK signaling pathway). Taken together, our results supported that the biological effects of BBP-activated integrin αvß3 mediated by the nongenomic pathway play an important role in its thyroid disruption. CAPSULE: The nongenomic pathway plays a vital role in the thyroid disruption-inducing actions of BBP.


Assuntos
Ácidos Ftálicos , Glândula Tireoide , Animais , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/toxicidade , Proteoma/metabolismo , Proteômica , Ratos , Peixe-Zebra/metabolismo
8.
Entropy (Basel) ; 24(4)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35455133

RESUMO

(1) Background and objective: Cardiovascular disease is one of the most common causes of death in today's world. ECG is crucial in the early detection and prevention of cardiovascular disease. In this study, an improved deep learning method is proposed to diagnose abnormal and normal ECG accurately. (2) Methods: This paper proposes a CNN-FWS that combines three convolutional neural networks (CNN) and recursive feature elimination based on feature weights (FW-RFE), which diagnoses abnormal and normal ECG. F1 score and Recall are used to evaluate the performance. (3) Results: A total of 17,259 records were used in this study, which validated the diagnostic performance of CNN-FWS for normal and abnormal ECG signals in 12 leads. The experimental results show that the F1 score of CNN-FWS is 0.902, and the Recall of CNN-FWS is 0.889. (4) Conclusion: CNN-FWS absorbs the advantages of convolutional neural networks (CNN) to obtain three parts of different spatial information and enrich the learned features. CNN-FWS can select the most relevant features while eliminating unrelated and redundant features by FW-RFE, making the residual features more representative and effective. The method is an end-to-end modeling approach that enables an adaptive feature selection process without human intervention.

10.
Environ Pollut ; 279: 116933, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33773180

RESUMO

Di(2-ethylhexyl) phthalate (DEHP), a manufactured chemical, is suitable for large-scale production and has extensive applications. Although restricted for use, DEHP is still ubiquitous in the environment and shows potential to disrupt the structure or function of the thyroid system. However, its toxic mechanism is complex and not clearly understood. In this study, a battery of methods was employed to investigate DEHP-induced thyroid-disrupting effects and their mechanism of action, focusing on a newly discovered membrane receptor-mediated mechanism. The results showed that DEHP promoted rat pituitary tumor (GH3) cell proliferation and c-fos gene expression at environment level concentrations (2 and 5 µmol/L) in a manner similar to that of the natural thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The macromolecule DEHP-BSA cannot pass through the cell membrane to interact with nuclear receptors but upregulated the c-fos gene expression when administered at concentrations comparable to DEHP concentrations; molecular docking demonstrated that DEHP has affinity for the membrane receptor integrin αvß3; DEHP at 2 µmol/L upregulated the ß3 gene expression in GH3 cells; after the addition of integrin αvß3-inhibiting RGD peptide, DEHP-induced c-fos gene upregulation decreased. All of these findings support the supposition that DEHP-induced thyroid-disrupting effects might be mediated by the membrane receptor integrin αvß3. Moreover, DEHP activated the downstream extracellular regulated protein kinase (ERK1/2) pathway, upregulating the gene expression of raf-1, MEK-1 and MAPK1 and increasing the protein levels of p-ERK; interestingly, ERK1/2 activation and c-fos upregulation induced by DEHP were attenuated by PD98059 (an ERK1/2 inhibitor). Taken together, the data suggest that the membrane receptor integrin αvß3 and the downstream ERK1/2 pathway might be involved in DEHP-induced thyroid-disrupting effects. This study provides new insight into the thyroid-disrupting effect and the underlying mechanism and will advance the effort to construct adverse outcome pathways of DEHP and other thyroid hormone disrupting chemicals.


Assuntos
Integrina alfaVbeta3 , Glândula Tireoide , Animais , Integrina alfaVbeta3/metabolismo , Sistema de Sinalização das MAP Quinases , Simulação de Acoplamento Molecular , Ratos , Glândula Tireoide/metabolismo , Hormônios Tireóideos
11.
Mol Plant ; 14(5): 774-786, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33601051

RESUMO

Nitrate-induced Ca2+ signaling is crucial for the primary nitrate response in plants. However, the molecular mechanism underlying the generation of the nitrate-specific calcium signature remains unknown. We report here that a cyclic nucleotide-gated channel (CNGC) protein, CNGC15, and the nitrate transceptor (NRT1.1) constitute a molecular switch that controls calcium influx depending on nitrate levels. The expression of CNGC15 is induced by nitrate, and its protein is localized at the plasma membrane after establishment of young seedlings. We found that disruption of CNGC15 results in the loss of the nitrate-induced Ca2+ signature (primary nitrate response) and retards root growth, reminiscent of the phenotype observed in the nrt1.1 mutant. We further showed that CNGC15 is an active Ca2+-permeable channel that physically interacts with the NRT1.1 protein in the plasma membrane. Importantly, we discovered that CNGC15-NRT1.1 interaction silences the channel activity of the heterocomplex, which dissociates upon a rise in nitrate levels, leading to reactivation of the CNGC15 channel. The dynamic interactions between CNGC15 and NRT1.1 therefore control the channel activity and Ca2+ influx in a nitrate-dependent manner. Our study reveals a new nutrient-sensing mechanism that utilizes a nutrient transceptor-channel complex assembly to couple nutrient status to a specific Ca2+ signature.


Assuntos
Proteínas de Transporte de Ânions/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Sinalização do Cálcio , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Canais de Potássio/metabolismo , Fenótipo , Transdução de Sinais
12.
Proc Natl Acad Sci U S A ; 117(26): 14751-14755, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32541031

RESUMO

The total amount of rainfall associated with tropical cyclones (TCs) over a given region is proportional to rainfall intensity and the inverse of TC translation speed. Although the contributions of increase in rainfall intensity to larger total rainfall amounts have been extensively examined, observational evidence on impacts of the recently reported but still debated long-term slowdown of TCs on local total rainfall amounts is limited. Here, we find that both observations and the multimodel ensemble of Global Climate Model simulations show a significant slowdown of TCs (11% in observations and 10% in simulations, respectively) from 1961 to 2017 over the coast of China. Our analyses of long-term observations find a significant increase in the 90th percentile of TC-induced local rainfall totals and significant inverse relationships between TC translation speeds and local rainfall totals over the study period. The study also shows that TCs with lower translation speed and higher rainfall totals occurred more frequently after 1990 in the Pearl River Delta in southern China. Our probability analysis indicates that slow-moving TCs are more likely to generate heavy rainfall of higher total amounts than fast-moving TCs. Our findings suggest that slowdown of TCs tends to elevate local rainfall totals and thus impose greater flood risks at the regional scale.

13.
Plant Signal Behav ; 15(3): 1729537, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32063094

RESUMO

Seed germination, a crucial developmental step, is regulated by multiple plant endogenous signals, among which phytohormones absisic acid (ABA) and gibberellin (GA) act antagonistically. Reactive oxygen species (ROS) interact with the two hormones to coordinate germination. We have previously reported that Arabidopsis glutamate receptor homolog3.5 (AtGLR3.5) modulates calcium signal to attenuate the repression effect of ABA on seed germination and that amino acid L-methionine functions upstream of AtGLR3.5, resulting in calcium influx. Here, we show that AtGLR3.5 modulates GA and ROS signaling during seed germination. Our findings provide a more complete picture as to the molecular mechanisms of AtGLR3.5 in seed germination control.


Assuntos
Arabidopsis/metabolismo , Germinação/fisiologia , Giberelinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Germinação/genética , Sementes/metabolismo , Sementes/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
14.
Sci Rep ; 10(1): 1677, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015470

RESUMO

Plant seed germination is a crucial developmental event that has significant effects on seedling establishment and yield production. This process is controlled by multiple intrinsic signals, particularly phytohormones. The gaseous hormone ethylene stimulates seed germination; however, the genetic basis of ethylene production in maize during seed germination remains poorly understood. In this study, we quantified the diversity of germination among 14 inbred lines representing the parental materials corresponding to multiple recombinant inbred line (RIL) mapping populations. Quantitative trait loci (QTLs) controlling ethylene production were then identified in germinating seeds from an RIL population constructed from two parental lines showing differences in both germination speed and ethylene production during germination. To explore the possible genetic correlations of ethylene production with other traits, seed germination and seed weight were evaluated using the same batch of samples. On the basis of high-density single nucleotide polymorphism-based genetic linkage maps, we detected three QTLs for ethylene production in germinating seeds, three QTLs for seed germination, and four QTLs for seed weight, with each QTL explaining 5.8%-13.2% of the phenotypic variation of the trait. No QTLs were observed to be co-localized, suggesting that the genetic bases underlying the three traits are largely different. Our findings reveal three chromosomal regions responsible for ethylene production during seed germination, and provide a valuable reference for the future investigation of the genetic mechanism underlying the role of the stress hormone ethylene in maize germination control under unfavourable external conditions.


Assuntos
Etilenos/metabolismo , Germinação/genética , Locos de Características Quantitativas/genética , Sementes/genética , Zea mays/genética , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Ligação Genética/genética , Genótipo , Fenótipo , Plântula/genética
15.
J Exp Bot ; 71(1): 178-187, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563952

RESUMO

Seed germination is a developmental process regulated by numerous internal and external cues. Our previous studies have shown that calcium influx mediated by the Arabidopsis glutamate receptor homolog 3.5 (AtGLR3.5) modulates the expression of the ABSCISIC ACID INSENSITIVE 4 (ABI4) transcription factor during germination and that L-methionine (L-Met) activates AtGLR3.1/3.5 Ca2+ channels in guard cells. However, it is not known whether L-Met participates in regulation of germination and what cellular mechanism is responsible for Met production during germination. Here, we describe Arabidopsis methionine synthase 1 (AtMS1), which acts in the final step of Met biosynthesis, synthesizes the Met required for the activation of AtGLR3.5 Ca2+ channels whose expression is up-regulated during germination, leading to the regulation of seed germination. We show that exogenous L-Met promotes germination in an AtGRL3.5-dependent manner. We also demonstrate that L-Met directly regulates the AtGLR3.5-mediated increase in cytosolic Ca2+ level in seedlings. We provide pharmacological and genetic evidence that Met synthesized via AtMS1 acts upstream of the AtGLR3.5-mediated Ca2+ signal and regulates the expression of ABI4, a major regulator in the abscisic acid response in seeds. Overall, our results link AtMS1, L-Met, the AtGLR3.5 Ca2+ channel, Ca2+ signals, and ABI4, and shed light on the physiological role and molecular mechanism of L-Met in germination.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Germinação/genética , Metionina/metabolismo , Receptores de Glutamato/genética , Fatores de Transcrição/genética , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Receptores de Glutamato/metabolismo , Fatores de Transcrição/metabolismo
16.
Comput Methods Programs Biomed ; 177: 183-192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31319947

RESUMO

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is one of the common cardiovascular diseases, and electrocardiography (ECG) is a key indicator for the detection and diagnosis of AF and other heart diseases. In this study, an improved machine learning method is proposed for rapid modeling and accurate diagnosis of AF. METHODS: This paper presents a novel IRBF-RVM model that combines the integrated radial basis function (IRBF) and relevance vector machine (RVM), which is utilized for the diagnosis of AF. The synchronous 12-lead ECG signals are collected from the human body surface so as to fully reflect the electrical activity of the whole heart. RR intervals of the QRS-waves in ECG signals are obtained by means of the classical Pan-Tompkins algorithm. The RR-features extracted from RR intervals are adopted as the diagnostic features for AF patients. In addition, the conventional RBF-RVM model, support vector machine (SVM) and other machine learning methods are also investigated for the diagnosis of AF so as to reflect the advantage of the proposed IRBF-RVM model. The open MIT-BIH arrhythmia database (MITDB) is also used to evaluate the predictive performance of these state-of-the-art methods. RESULTS: Altogether 1056 AF patients and 904 healthy people are participated in this study and validate the effectiveness of each channel of the 12-lead ECG signals. Experimental results show that the classification rate of IRBF-RVM can reach up to 98.16% by recurring to Channel II of the 12-lead ECG signals. CONCLUSIONS: IRBF-RVM absorbs the advantages of IRBF, which makes the kernel parameter of IRBF-RVM have a much larger selectable region than RBF-RVM. In addition, RVM has faster modeling and recognition speed in comparison with SVM. This work lays the foundation for the application of RVM to accurate diagnosis of AF.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Diagnóstico por Computador , Eletrocardiografia , Processamento de Sinais Assistido por Computador , Máquina de Vetores de Suporte , Teorema de Bayes , Coleta de Dados , Bases de Dados Factuais , Cardiopatias , Humanos , Modelos Estatísticos , Distribuição Normal , Probabilidade , Reprodutibilidade dos Testes
17.
Chemosphere ; 212: 1058-1066, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30286535

RESUMO

Di-n-butylphthalate (DnBP) exhibits alarming thyroid disrupting activities. However, the toxic mechanism of DnBP is not completely understood. In this study, we investigated the mechanism of DnBP in thyroid disruption. Rat pituitary tumor cell lines (GH3) were treated with DnBP in different scenarios, and cell viabilities, target gene transcriptions and protein levels were measured accordingly. The results showed that after treatment with DnBP (20 µmol/L), cell proliferation increased to 114.69% (p < 0.01) and c-fos gene was up-regulated by 1.57-fold (p < 0.01). Both nuclear thyroid hormone receptor ß (TRß) and membrane TR (integrin αv and integrin ß3) genes were up-regulated by 1.31-, 1.08- and 2.39-fold (p < 0.01), respectively, the latter was inhibited by Arg-Gly-Asp (RGD) peptides; the macromolecular DnBP-BSA was unable to bind nuclear TRs, but still promoted cell proliferation to 104.18% and up-regulated c-fos by 2.99-fold (p < 0.01); after silencing TRß gene, cell proliferation (106.64%, p < 0.05) and up-regulation of c-fos (1.23-fold, p < 0.01) were also observed. All of these findings indicated the existence of non-genomic pathway for DnBP-induced thyroid disruption. Finally, DnBP activated the downstream extracellular regulated protein kinases (ERK1/2) pathway, up-regulating Mapk1 (1.15-, p < 0.05), Mapk3 (1.26-fold, p < 0.01) and increasing protein levels of p-ERK (p < 0.01); notably, DnBP-induced ERK1/2 activation along with c-fos up-regulation were attenuated by PD98059 (ERK1/2 inhibitor). Taken together, it could be suggested that integrin αvß3 and ERK1/2 pathway play significant roles in DnBP-induced thyroid disruption, and this novel mechanism warrants further investigation in living organisms.


Assuntos
Benzofuranos/toxicidade , Proliferação de Células , Integrina alfaVbeta3/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ratos , Glândula Tireoide/metabolismo
18.
Plant Cell Environ ; 40(9): 1834-1848, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28556250

RESUMO

Nitric oxide (NO) is extensively involved in various growth processes and stress responses in plants; however, the regulatory mechanism of NO-modulated cellular sugar metabolism is still largely unknown. Here, we report that NO significantly inhibited monosaccharide catabolism by modulating sugar metabolic enzymes through S-nitrosylation (mainly by oxidizing dihydrolipoamide, a cofactor of pyruvate dehydrogenase). These S-nitrosylation modifications led to a decrease in cellular glycolysis enzymes and ATP synthase activities as well as declines in the content of acetyl coenzyme A, ATP, ADP-glucose and UDP-glucose, which eventually caused polysaccharide-biosynthesis inhibition and monosaccharide accumulation. Plant developmental defects that were caused by high levels of NO included delayed flowering time, retarded root growth and reduced starch granule formation. These phenotypic defects could be mediated by sucrose supplementation, suggesting an essential role of NO-sugar cross-talks in plant growth and development. Our findings suggest that molecular manipulations could be used to improve fruit and vegetable sweetness.


Assuntos
Arabidopsis/metabolismo , Monossacarídeos/metabolismo , Óxido Nítrico/farmacologia , Complexos de ATP Sintetase/metabolismo , Adenosina Difosfato Glucose/metabolismo , Trifosfato de Adenosina/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/enzimologia , Glicólise/efeitos dos fármacos , Mutação/genética , Nitrosação , Oxirredução , Fenótipo , Desenvolvimento Vegetal/efeitos dos fármacos , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Solubilidade , Amido/metabolismo , Sacarose/farmacologia , Ácido Tióctico/análogos & derivados , Ácido Tióctico/metabolismo , Uridina Difosfato Glucose/metabolismo
19.
Plant Physiol ; 174(2): 1274-1284, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28450424

RESUMO

Folates, termed from tetrahydrofolate (THF) and its derivatives, function as coenzymes in one-carbon transfer reactions and play a central role in synthesis of nucleotides and amino acids. Dysfunction of cellular folate metabolism leads to serious defects in plant development; however, the molecular mechanisms of folate-mediated cellular modifications and physiological responses in plants are still largely unclear. Here, we reported that THF controls flowering time by adjusting DNA methylation-regulated gene expression in Arabidopsis (Arabidopsis thaliana). Wild-type seedlings supplied with THF as well as the high endogenous THF content mutant dihydrofolate synthetase folypoly-Glu synthetase homolog B exhibited significant up-regulation of the flowering repressor of Flowering Wageningen and thereby delaying floral transition in a dose-dependent manner. Genome-wide transcripts and DNA methylation profiling revealed that THF reduces DNA methylation so as to manipulate gene expression activity. Moreover, in accompaniment with elevated cellular ratios between monoglutamylated and polyglutamylated folates under increased THF levels, the content of S-adenosylhomo-Cys, a competitive inhibitor of methyltransferases, was obviously higher, indicating that enhanced THF accumulation may disturb cellular homeostasis of the concerted reactions between folate polyglutamylation and folate-dependent DNA methylation. In addition, we found that the loss-of-function mutant of CG DNA methyltransferase MET1 displayed much less responsiveness to THF-associated flowering time alteration. Taken together, our studies revealed a novel regulatory role of THF on epigenetic silencing, which will shed lights on the understanding of interrelations in folate homeostasis, epigenetic variation, and flowering control in plants.


Assuntos
Arabidopsis/genética , Arabidopsis/fisiologia , Epigênese Genética/efeitos dos fármacos , Flores/genética , Inativação Gênica/efeitos dos fármacos , Tetra-Hidrofolatos/farmacologia , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Flores/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta , Ácido Poliglutâmico/metabolismo
20.
Huan Jing Ke Xue ; 38(1): 195-200, 2017 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965047

RESUMO

A rapid recombinant human thyroid (hTR) gene yeast bioassay was used to evaluate the effect of dissolved humic acid on thyroid receptor antagonistic activity of ZnCl2.The concentration of bio-available zinc after its reaction with dissolved humic acids was measured by anodic stripping voltammetry (ASV).Furthermore,the reaction mechanism of humic acid and zinc was investigated by three-dimensional excitation-emission matrix fluorescence spectroscopy (3DEEM).The results revealed that ZnCl2 demonstrated strong thyroid receptor antagonistic activity,and the concentration inhibiting 20% of the maximum effect of ZnCl2 was 1.70×10-5 mol·L-1.The thyroid receptor antagonistic activity of ZnCl2 was reduced by 30%-50% after the reaction of dissolved humic acids.The results of ASV showed that the concentration of bio-available zinc was decreased after the reaction of dissolved humic acids,the result was similar to that of bioassay test.The thyroid receptor antagonistic activity of the mixed solution of humic acid and ZnCl2 was increased after UV radiation treatment,however it was still lower than the antagonistic activity induced by ZnCl2.The results of 3DEEM showed that ZnCl2 could reduce the fluorescence peak intensity of humic acid,which could intuitively characterize the interaction between humic acid and ZnCl2.The above results can provide basic data and theoretical support for zinc toxicity study in aquatic environment and the establishment of water quality criteria for znic.


Assuntos
Cloretos/efeitos adversos , Substâncias Húmicas/análise , Receptores dos Hormônios Tireóideos/antagonistas & inibidores , Poluentes Químicos da Água/efeitos adversos , Compostos de Zinco/efeitos adversos , Bioensaio , Humanos , Espectrometria de Fluorescência , Qualidade da Água , Leveduras , Zinco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA