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1.
Nat Immunol ; 14(7): 714-22, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23708251

RESUMO

GATA-3 controls T helper type 2 (TH2) differentiation. However, whether GATA-3 regulates the function of mature T cells beyond TH2 determination remains poorly understood. We found that signaling via the T cell antigen receptor (TCR) and cytokine stimulation promoted GATA-3 expression in CD8(+) T cells, which controlled cell proliferation. Although GATA-3-deficient CD8(+) T cells were generated, their peripheral maintenance was impaired, with lower expression of the receptor for interleukin 7 (IL-7R). GATA-3-deficient T cells had defective responses to viral infection and alloantigen. The proto-oncoprotein c-Myc was a critical target of GATA-3 in promoting T cell proliferation. Our study thus demonstrates an essential role for GATA-3 in controlling the maintenance and proliferation of T cells and provides insight into immunoregulation.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Fator de Transcrição GATA3/imunologia , Ativação Linfocitária/imunologia , Proteínas Proto-Oncogênicas c-myc/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Interleucina-7/imunologia , Animais , Proliferação de Células , Imunoprecipitação da Cromatina , Citometria de Fluxo , Doença Enxerto-Hospedeiro/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Stat Appl Genet Mol Biol ; 23(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363177

RESUMO

Developments in biotechnologies enable multi-platform data collection for functional genomic units apart from the gene. Profiling of non-coding microRNAs (miRNAs) is a valuable tool for understanding the molecular profile of the cell, both for canonical functions and malignant behavior due to complex diseases. We propose a graphical mixed-effects statistical model incorporating miRNA-gene target relationships. We implement an integrative pathway analysis that leverages measurements of miRNA activity for joint analysis with multimodal observations of gene activity including gene expression, methylation, and copy number variation. We apply our analysis to a breast cancer dataset, and consider differential activity in signaling pathways across breast tumor subtypes. We offer discussion of specific signaling pathways and the effect of miRNA integration, as well as publish an interactive data visualization to give public access to the results of our analysis.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/metabolismo , Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica , Metilação de DNA/genética , Expressão Gênica , Regulação Neoplásica da Expressão Gênica
3.
Nano Lett ; 24(5): 1594-1601, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38134416

RESUMO

Blue quantum dot (QD) light-emitting diodes (QLEDs) exhibit unsatisfactory operational stability and electroluminescence (EL) properties due to severe nonradiative recombination induced by large numbers of dangling bond defects and charge imbalance in QD. Herein, dipolar aromatic amine-functionalized molecules with different molecular polarities are employed to regulate charge transport and passivate interfacial defects between QD and the electron transfer layer (ETL). The results show that the stronger the molecular polarity, especially with the -CF3 groups possessing a strong electron-withdrawing capacity, the more effective the defect passivation of S and Zn dangling bonds at the QD surface. Moreover, the dipole interlayer can effectively reduce electron injection into QD at high current density, enhancing charge balance and mitigating Joule heat. Finally, blue QLEDs exhibit a peak external quantum efficiency (EQE) of 21.02% with an operational lifetime (T50 at 100 cd m-2) exceeding 4000 h.

4.
Immunity ; 42(1): 68-79, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25577439

RESUMO

Transforming growth factor-beta (TGF-ß) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-ß signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-ßR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-ßR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad4/metabolismo , Subpopulações de Linfócitos T/fisiologia , Linfócitos T Reguladores/fisiologia , Animais , Autoimunidade/genética , Proliferação de Células/genética , Células Cultivadas , Tolerância Imunológica/genética , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Proteína Smad4/genética , Subpopulações de Linfócitos T/transplante , Linfócitos T Reguladores/transplante , Quimeras de Transplante , Evasão Tumoral
5.
Int J Mol Sci ; 24(6)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36982900

RESUMO

Chlorophyll drives plant photosynthesis. Under stress conditions, leaf chlorophyll content changes dramatically, which could provide insight into plant photosynthesis and drought resistance. Compared to traditional methods of evaluating chlorophyll content, hyperspectral imaging is more efficient and accurate and benefits from being a nondestructive technique. However, the relationships between chlorophyll content and hyperspectral characteristics of wheat leaves with wide genetic diversity and different treatments have rarely been reported. In this study, using 335 wheat varieties, we analyzed the hyperspectral characteristics of flag leaves and the relationships thereof with SPAD values at the grain-filling stage under control and drought stress. The hyperspectral information of wheat flag leaves significantly differed between control and drought stress conditions in the 550-700 nm region. Hyperspectral reflectance at 549 nm (r = -0.64) and the first derivative at 735 nm (r = 0.68) exhibited the strongest correlations with SPAD values. Hyperspectral reflectance at 536, 596, and 674 nm, and the first derivatives bands at 756 and 778 nm, were useful for estimating SPAD values. The combination of spectrum and image characteristics (L*, a*, and b*) can improve the estimation accuracy of SPAD values (optimal performance of RFR, relative error, 7.35%; root mean square error, 4.439; R2, 0.61). The models established in this study are efficient for evaluating chlorophyll content and provide insight into photosynthesis and drought resistance. This study can provide a reference for high-throughput phenotypic analysis and genetic breeding of wheat and other crops.


Assuntos
Clorofila , Imageamento Hiperespectral , Triticum/genética , Secas , Melhoramento Vegetal , Folhas de Planta
6.
J Environ Manage ; 324: 116255, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36352707

RESUMO

Simulation-based optimization (S-O) frameworks are effective in developing cost-effective watershed management strategies, where optimization algorithms have substantial effect on the quality of strategies. Despite the development and improvement of multi-objective evolutionary algorithms (MOEAs) provide more robust alternatives for optimization, they typically have limited applications in real-world decision contexts. In this study, three advanced MOEAs, including NSGA-II, MOEA/D and NSGA-III, were introduced into the S-O framework and applied to a real-world watershed management problem, and their performance and characteristics were quantified through performance metrics. Results show that a higher crossover or mutation probability do not necessarily promote convergence and diversity of solutions, while a larger generation and population size is helpful for MOEAs to find high-quality solutions. Compared to the other two MOEAs, NSGA-II consistently exhibits robust performance in finding solutions with good convergence and high diversity, and provides more options at the same computational cost, while the degenerate Pareto front of the proposed watershed management problem may account for the poor performance of MOEA/D and NSGA-III in terms of diversity. For a 10% TN or TP reduction target, the average cost of the NSGA-II optimized strategies is 32.22% or 47.83% of the commonly used strategies. In addition, this study also discussed the development of resilient watershed management to buffer the impacts of climate change on aquatic system, the incorporation of fuzzy programming into the S-O framework to develop robust watershed management strategies under uncertainty, and the application of machine learning-based surrogate models to reduce computational cost of the S-O framework. These results can contribute to the understanding of MOEAs and provide useful guidance to decision makers.


Assuntos
Algoritmos , Mudança Climática , Recursos Hídricos , Simulação por Computador , Incerteza
7.
Phys Biol ; 18(2): 026005, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33395673

RESUMO

An important feature of the branch morphogenesis during kidney development is the termination of the tips on the outer surface of a kidney. This feature requires the avoidance of the intersection between the tips and existing ducts inside the kidney. Here, we started from a continuous model and implemented the coarse grained rules into a fast and discrete simulations. The ligand-receptor-based Turing mechanism suggests a repulsion that decreases exponentially with distance between interacting branches, preventing the intersection between neighboring branches. We considered this repulsive effect in numerical simulations and successfully reproduce the key features of the experimentally observed branch morphology for an E15.5 kidney. We examine the similarity of several geometrical parameters between the simulation results and experimental observations. The good agreement between the simulations and experiments suggests that the concentration decay caused by the absorption of glial cell line derived neurotrophic factor might be the key factor to affect the geometry in early kidney development.


Assuntos
Rim/crescimento & desenvolvimento , Morfogênese , Transdução de Sinais , Animais , Rim/embriologia , Camundongos , Modelos Biológicos
8.
Ecotoxicol Environ Saf ; 215: 112152, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33780781

RESUMO

The relationship between soil respiration (SR) and microbial community structure (MCS) is relevant to changes in forest soil ecosystem stability and chemical cycling under acid rain. Simulated acid rain treatments of pH 4.5 (control), 4.0, 3.25 and 2.5 were applied to two forest stands in the Three Gorges Reservoir Area of Jinyun Mountain, Chongqing. We used phospholipid fatty acid (PLFA) analysis to observe the MCS in the 0-10 cm soil layer and measured SR in situ from January 2016 to December 2017. Additionally, we determined the effects of soil properties on the MCS and SR. Acid rain simulation significantly increased the fungal PLFA abundance and decreased the bacterial PLFA abundance in the mixed coniferous and broad-leaved forest (CF). However, in the evergreen broad-leaved forest (BF), the abundance of bacterial and fungal PLFAs did not differ significantly among treatments. Redundancy analysis (RDA) showed that significant changes in the MSC were mainly due to the C/N ratio, hydrolysable N content, content, fine root biomass and sucrase activity. Acid rain simulation in the CF and BF significantly inhibited SR, but the SR sensitivity to simulated acid rain differed among forests. In 2017, the annual mean SR in the CF under the pH 4.0, 3.25 and 2.5 treatments decreased significantly by 6.1%, 19.2% and 28.9%, but in the BF, SR decreased significantly by 25.6% only under pH 2.5. The structural equation model showed that the relationship between the MCS and the variation in SR was closer and more direct than that with soil nutrients. The microbial community structure was an important factor driving the response of soil respiration to acid rain.


Assuntos
Chuva Ácida , Florestas , Microbiologia do Solo , Bactérias , Biomassa , China , Fungos , Microbiota , Respiração , Solo/química
9.
Ecotoxicol Environ Saf ; 208: 111457, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33120255

RESUMO

The chemical composition in the precipitation is constantly changing, thus acid rain type is gradually changing from sulfuric type to mixed type and then nitric type. The influence of the changing acid rain type on the rhizosphere soil of tree species remains unclear. A pot experiment was performed with two-year-old Pinus massoniana, Cunninghamia lanceolate, Cyclobalanpsis glauca and Phyllostachys edulis seedlings with similar growth condition. Simulated acid rain consists of sulfuric(S/N = 5), mixed(S/N = 1) and nitric(S/N = 0.2) acid rain, and each type acid rain diluted to three acid rain intensity: pH = 2.5, 3.5, 4.5. Soil pH, soil organic matter, cation exchange capacity, the exchangeable Na+, K+, Ca2+, Mg2+ and enzyme activity were inhibited by acid rain intensity, while exchangeable Al3+ and H+ were promoted. Mg2+ was most relevant index to the tolerance to acid rain and the correlation degree of soil chemical index was higher than that of enzyme activity. Response of soil chemical properties differed in tree species under different acid rain types. Soil enzyme activity of Pinus massoniana, Cunninghamia lanceolate, and Phyllostachys edulis reached lowest under nitric acid rain, and that of Cyclobalanpsis glauca reached highest. Rhizosphere soil of Cunninghamia lanceolate is tolerant to sulfuric and nitric acid rain, and that of Cyclobalanpsis glauca is tolerant to mixed acid rain.


Assuntos
Monitoramento Ambiental , Microbiologia do Solo , Chuva Ácida , China , Cunninghamia/crescimento & desenvolvimento , Ácido Nítrico , Pinus , Poaceae , Rizosfera , Plântula/crescimento & desenvolvimento , Solo/química , Árvores
10.
J Environ Manage ; 290: 112659, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33894485

RESUMO

Low-carbon power generation has been proposed as the key to address climate change. However, the sustainability and ecological efficiency of the generating plants have not been fully understood. This study applies emergy analysis and systems accounting to a pilot solar power tower plant in China for the first time to elaborate its sustainable and ecological performances. Emergy analysis covers virtually all aspects of sustainability and ecological efficiency by considering different forms of materials inputs, environmental support and human labor on the same unit of "solar joule". The input-output analysis based systems accounting is applied to trace the complete emergy embodied in the supply chain for all product materials of the given plant against the back ground of complex economic network, which improved the accuracy of accounting. This analysis illustrated unexpectedly low sustainability and ecological efficiency of this particular plant compared with the emergy analysis based on the primary materials (steel, iron, cement, etc.). Purchased emergy responses more than 95% of the total and emergy input in the construction phase is more than twice as much as that in the operation phase. Comparisons with other kinds of clean energy technologies indicate previous studies may have overestimated the sustainability and ecological benefits of low-carbon power plants. Thus, it is necessary to establish this kind of unified accounting framework. In addition, sensitivity analysis suggests that strictly controlling monetary costs of purchased inputs, extending service lifetime and improving power generation efficiency can promote higher sustainability and ecological efficiency for solar power tower plants. This study provides a more comprehensive framework for quantitative emergy-based evaluation of the sustainability and ecological efficiency for low-carbon power systems.


Assuntos
Conservação dos Recursos Naturais , Energia Solar , Carbono , China , Ecossistema , Humanos , Centrais Elétricas
11.
J Neurosci ; 39(33): 6439-6448, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31209171

RESUMO

Abacus-based mental calculation (AMC) involves temporary storage and manipulation of an imaginary abacus closely related to the function of visuospatial working memory (VSWM). The present study thus investigated the effects of AMC training on VSWM and its neural correlates. A total of 144 human subjects (67 boys) were assigned to AMC or control groups at their entry to primary school. The AMC group received 2 h AMC training per week for 5 school years, whereas the control group spent the time in activities, such as conventional calculation and reading. Raven's Intelligence Test was administered both before and after training. Two arithmetic tests and a VSWM task were conducted after training. Among these participants, fMRI data were collected from 64 children for the VSWM task. Behavioral results indicated that the AMC group outperformed controls on both arithmetic and VSWM tasks, but not on Raven's Intelligence Test. While the two groups activated similar regions during the VSWM task, the AMC group showed greater activation than the controls in frontal, parietal, and occipital areas. Interestingly, the activation of right middle frontal gyrus mediated the relation between the arithmetic ability and the VSWM performance in the AMC group, suggesting that the frontal region may be the neural substrate underlying the transfer effect from AMC training to VSWM. Although the transfer effects seem quite limited considering the length and intensity of the training, these findings suggest that long-term AMC training not only improves arithmetic ability but also has a potential positive effect on VSWM.SIGNIFICANCE STATEMENT Plasticity of working memory is one of the most rapidly expanding research fields in the developmental and cognitive sciences. Previous studies suggest that abacus-based mental calculation (AMC) relies on a visuospatial imaginary strategy, which is closely related to visuospatial working memory (VSWM). However, the impacts of AMC training on VSWM and the underlying neural basis remain unclear. Here, we found that AMC training enhanced VSWM in children, which was accompanied by altered activation in frontal, parietal, and occipital areas. Moreover, we observed that activation in right middle frontal gyrus played a significant mediation role in the transfer of AMC training to VSWM. These findings provide a new perspective to VSWM training and also advance our understanding of related brain plasticity.


Assuntos
Encéfalo/fisiologia , Aprendizagem/fisiologia , Memória de Curto Prazo/fisiologia , Plasticidade Neuronal/fisiologia , Ensino , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Matemática , Materiais de Ensino
12.
Immunity ; 35(3): 337-48, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21924928

RESUMO

Forkhead Box P3 (Foxp3)-expressing regulatory T (Treg) cells are central to maintaining self-tolerance and immune homeostasis. How Treg cell function and Foxp3 expression are regulated is an important question under intensive investigation. Here, we have demonstrated an essential role for the transcription factor GATA-3, a previously recognized Th2 cell master regulator, in controlling Treg cell function. Treg cell-specific GATA-3 deletion led to a spontaneous inflammatory disorder in mice. GATA-3-null Treg cells were defective in peripheral homeostasis and suppressive function, gained Th17 cell phenotypes, and expressed reduced amounts of Foxp3. In addition, GATA-3 controlled Foxp3 expression by binding to and promoting the activity of cis-acting elements of Foxp3. Furthermore, the combined function of GATA-3 and Foxp3 was essential for Foxp3 expression. These findings provide insights into immune regulatory mechanisms and uncover a critical function of GATA-3 in Treg cells and immune tolerance.


Assuntos
Fator de Transcrição GATA3/genética , Regulação da Expressão Gênica , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Animais , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Regulação para Baixo , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Homeostase/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica , Linfócitos T Reguladores/citologia
13.
Environ Res ; 189: 109893, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32979998

RESUMO

Microplastics pollution presents an increasing concern worldwide due to the large amount and potential risks. However, data on microplastics in the freshwater environment are still limited, especially in southwest China. This study investigated the microplastics distribution, characteristics and risks in urban water of different cities in the Tuojiang River basin in southwest China. Microplastics were found in all seven cities of the Tuojiang River basin and the concentrations varied from 911.57 ± 199.73 to 3395.27 ± 707.22 items/m3, among which Ziyang urban water had the highest microplastics concentration. Fiber (34.88-65.85%) was a typical and abundant microplastic type. The small size (0.5-1 mm) (27.27-66.67%) was predominant, and white (23.30-54.29%) was the dominant color among all samples. Polypropylene was identified as the main polymer type by Fourier transform infrared spectroscopy. The morphological analysis by scanning electron microscopy indicated that the surfaces of the microplastics had many cracks and a multitude of particles were adsorbed onto it. According to correlation analysis, there was a significant positive correlation between gross domestic product(P=0.015<0.05) and gross domestic product of the secondary industries(P=0.014<0.05) of cities in the Tuojiang River basin and microplastics concentrations, demonstrating impacts of the secondary industries on the microplastics pollution. In addition, water bodies with lower oxidation-reduction potential tended to have higher microplastics abundance. In the Tuojiang River basin, microplastics pollution was more serious in location where water quality was poor. The polymer risk index (H) was calculated to assess the environmental risk of microplastics in different cities, and the results showed that Fushun sites had the highest risk in regard to microplastics. This study provides a valuable reference for a better understanding of the microplastics level and source identification in southwest China.


Assuntos
Rios , Poluentes Químicos da Água , China , Cidades , Monitoramento Ambiental , Microplásticos , Plásticos , Poluentes Químicos da Água/análise
14.
Sensors (Basel) ; 20(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731546

RESUMO

The health and environmental effects of particulate matter (PM) in the air depend on several parameters. Besides particle size, shape, and concentration, the chemical nature of the PM is also of great importance. State-of-the-art PM sensors only detect the particle size and concentration. Small, low-cost sensors only identify PM according to PM2.5 and PM10 standards. Larger detectors measure the complete particle size distribution. However, the chemical composition of PM is not often assessed. The current paper presents the initial stages of the development of an infrared-based detector for the inline assessment of the chemistry of PM in the air. By combining a mini cyclone that is able to concentrate the particles at least a thousand fold and a hollow waveguide that aligns the flow of particles with infrared light, the feasibility of the concept was shown in this study. A clear differentiation between amorphous and crystalline silica was demonstrated at outdoor PM levels of lower than 1 mg per cubic meter.

15.
Anal Bioanal Chem ; 411(24): 6419-6426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392437

RESUMO

Amine-functionalized silicon nanoparticles (A-SiNPs) with intense green fluorescence and photostability are synthesized via a one-step, low-cost hydrothermal method under mild conditions using 3-aminopropyl triethoxysilane (APTES) as a silicon source and L-ascorbic acid (AA) as a reducing reagent. The amine-rich surface not only improves water dispersability and stability of the A-SiNPs but also offers a specific copper(II) ion (Cu2+) coordination capability. The as-prepared A-SiNPs can be directly employed for Cu2+ detection in "turn-off" mode, resulting from Cu2+ coordination-induced fluorescence quenching effect. Under optimal conditions, Cu2+ detection was accomplished with a linear range from 1 to 500 µM and a limit of detection (LOD) at 0.1 µM, which was much lower than the maximum level (~ 20 µM) of Cu2+ in drinking water permitted by the US Environmental Protection Agency (EPA). In addition, the A-SiNPs were successfully used to detect Cu2+ in spiked river water, demonstrating its good selectivity and potential application for analysis of surface water samples. Graphical abstract.

16.
Appl Microbiol Biotechnol ; 103(12): 5051-5059, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31001744

RESUMO

The effects of two nitrogen (N) concentrations combining with three phosphorus (P) concentrations on Isochrysis zhangjiangensis growth and formation of fatty acid (FA) were investigated in this study. Biomass concentration, mass fraction, and productivity of FA in I. zhangjiangensis were low in N-deprived media. Under both N and P sufficiency conditions, the intake of P and N was 40 times and 4.7 times of the normal algal growth condition, respectively, indicating I. zhangjiangensis had the potential for removing P and N from high concentrated N and P salinity wastewater. This study also showed that P deficiency in N sufficient medium increased the FA content, however, the difference between P limitation and P deprivation was not significant (P > 0.05). In N sufficient and P limitation medium, FA productivity was the highest, with a composition suitable for biofuel, so, this condition was the optimal condition for biodiesel production from I. zhangjiangensis.


Assuntos
Biocombustíveis/análise , Haptófitas/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Biocombustíveis/microbiologia , Biomassa , Meios de Cultura/química , Ácidos Graxos/análise , Haptófitas/crescimento & desenvolvimento , Águas Residuárias/microbiologia
17.
Cell Physiol Biochem ; 46(2): 654-663, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617683

RESUMO

BACKGROUND/AIMS: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. METHODS: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and ß-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. RESULTS: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3' UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. CONCLUSION: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Células A549 , Antagomirs/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina E/genética , Ciclina E/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular
18.
J Med Virol ; 90(7): 1199-1209, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29508932

RESUMO

Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4+ and CD8+ T cells. The numbers of CD4+ and CD8+ T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4+ and CD8+ T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4+ and CD8+ T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4+ T cells counts and ratio of CD4+ /CD8+ T cells decreased while CD8+ T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4+ and CD8+ T cells at acute and chronic stage with the criterial of P-value <0.05 and fold change (FC) ≥2; 3) In acute HIV infection, type 1 interferon (IFN-1) pathway might played a critical role in response to HIV infection of T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4+ T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4+ and CD8+ T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Perfilação da Expressão Gênica , Infecções por HIV/patologia , HIV/imunologia , Interações Hospedeiro-Patógeno , Biologia Computacional , Humanos
19.
J Immunol ; 197(11): 4325-4333, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27799308

RESUMO

Bromodomain PHD finger transcription factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. Although BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late double-negative 3/double-negative 4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell-intrinsic manner. In addition, BPTF was essential for the maintenance and function of regulatory T (Treg) cells. Treg cell-specific BPTF deletion led to reduced Foxp3 expression, increased lymphocyte infiltration in the nonlymphoid organs, and a systemic autoimmune syndrome. These findings therefore reveal a vital role for BPTF in T and Treg cell function and immune homeostasis.


Assuntos
Antígenos Nucleares/imunologia , Regulação da Expressão Gênica/imunologia , Homeostase/imunologia , Proteínas do Tecido Nervoso/imunologia , Linfócitos T Reguladores/imunologia , Fatores de Transcrição/imunologia , Animais , Antígenos Nucleares/genética , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Fatores de Transcrição Forkhead/imunologia , Homeostase/genética , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Síndrome , Fatores de Transcrição/genética
20.
Sensors (Basel) ; 18(10)2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30274309

RESUMO

The geomagnetic field is as fundamental a constituent of passive navigation as Earth's gravity. In cases where no other external attitude reference is available, for the direct heading angle estimation by a typical magnetic compass, a two-step optimized correction algorithm is proposed to correct the model coefficients caused by hard and soft iron nearby. Specifically, in Step 1, a Levenberg-Marquardt (L-M) fitting estimator with an ellipsoid constraint is applied to solve the hard magnetic coefficients. In Step 2, a Lagrange multiplier estimator is used to deal with the soft magnetic iron circumstance. The essential attribute of "the two-step" lies in its eliminating the coupling effects of hard and soft magnetic fields, and their mutual interferences on the pure geomagnetic field. Under the conditions of non-deterministic magnetic interference sources with noise, the numerical simulation by referring to International Geomagnetic Reference Field (IGRF), and the laboratory tests based upon the turntable experiments with Honeywell HMR3000 compass (Honeywell, Morristown, NJ, USA) conducted, the experimental results indicate that, in the presence of the variation of multi-magnetic interferences, the RMSE (Root Mean Square Error) value of the estimated total magnetic flux density by the proposed two-step estimator falls to 0.125 µT from its initial 2.503 µT, and the mean values of the heading angle error estimates are less than 1°. The proposed solution therefore, exhibits ideal convergent properties, fairly meeting the accuracy requirements of non-tactical level navigation applications.

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