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1.
Plant Cell ; 35(5): 1572-1592, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36762404

RESUMO

Mitogen-activated protein (MAP) kinase signaling cascades play important roles in eukaryotic defense against various pathogens. Activation of the extracellular ATP (eATP) receptor P2K1 triggers MAP kinase 3 and 6 (MPK3/6) phosphorylation, which leads to an elevated plant defense response. However, the mechanism by which P2K1 activates the MAPK cascade is unclear. In this study, we show that in Arabidopsis thaliana, P2K1 phosphorylates the Raf-like MAP kinase kinase kinase (MAPKKK) INTEGRIN-LINKED KINASE 5 (ILK5) on serine 192 in the presence of eATP. The interaction between P2K1 and ILK5 was confirmed both in vitro and in planta and their interaction was enhanced by ATP treatment. Similar to P2K1 expression, ILK5 expression levels were highly induced by treatment with ATP, flg22, Pseudomonas syringae pv. tomato DC3000, and various abiotic stresses. ILK5 interacts with and phosphorylates the MAP kinase MKK5. Moreover, phosphorylation of MPK3/6 was significantly reduced upon ATP treatment in ilk5 mutant plants, relative to wild-type (WT). The ilk5 mutant plants showed higher susceptibility to P. syringae pathogen infection relative to WT plants. Plants expressing only the mutant ILK5S192A protein, with decreased kinase activity, did not activate the MAPK cascade upon ATP addition. These results suggest that eATP activation of P2K1 results in transphosphorylation of the Raf-like MAPKKK ILK5, which subsequently triggers the MAPK cascade, culminating in activation of MPK3/6 associated with an elevated innate immune response.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , MAP Quinase Quinase Quinases/genética , Proteínas de Arabidopsis/metabolismo , Imunidade Inata , Receptores Purinérgicos/metabolismo , Trifosfato de Adenosina/metabolismo , Pseudomonas syringae/fisiologia , Regulação da Expressão Gênica de Plantas , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Imunidade Vegetal/genética
2.
Nano Lett ; 24(20): 6038-6042, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38735063

RESUMO

Polymer nanofibers hold promise in a wide range of applications owing to their diverse properties, flexibility, and cost effectiveness. In this study, we introduce a polymer nanofiber drawing process in a scanning electron microscope and focused ion beam (SEM/FIB) instrument with in situ observation. We employed a nanometer-sharp tungsten needle and prepolymer microcapsules to enable nanofiber drawing in a vacuum environment. This method produces individual polymer nanofibers with diameters as small as ∼500 nm and lengths extending to millimeters, yielding nanofibers with an aspect ratio of 2000:1. The attachment to the tungsten manipulator ensures accurate transfer of the polymer nanofiber to diverse substrate types as well as fabrication of assembled structures. Our findings provide valuable insights into ultrafine polymer fiber drawing, paving the way for high-precision manipulation and assembly of polymer nanofibers.

3.
PLoS Genet ; 17(7): e1009678, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260587

RESUMO

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larvae and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-ß locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adaptação Fisiológica/genética , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Ciclo Celular , Processos de Crescimento Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Larva/genética , Larva/crescimento & desenvolvimento , Feromônios/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologia
4.
Sensors (Basel) ; 24(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732799

RESUMO

Additive manufacturing (AM) technology has recently seen increased utilization due to its versatility in using functional materials, offering a new pathway for next-generation conformal electronics in the smart sensor field. However, the limited availability of polymer-based ultraviolet (UV)-curable materials with enhanced piezoelectric properties necessitates the development of a tailorable process suitable for 3D printing. This paper investigates the structural, thermal, rheological, mechanical, and piezoelectric properties of a newly developed sensor resin material. The polymer resin is based on polyvinylidene fluoride (PVDF) as a matrix, mixed with constituents enabling UV curability, and boron nitride nanotubes (BNNTs) are added to form a nanocomposite resin. The results demonstrate the successful micro-scale printability of the developed polymer and nanocomposite resins using a liquid crystal display (LCD)-based 3D printer. Additionally, incorporating BNNTs into the polymer matrix enhanced the piezoelectric properties, with an increase in the voltage response by up to 50.13%. This work provides new insights for the development of 3D printable flexible sensor devices and energy harvesting systems.

5.
Int J Mol Sci ; 25(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38673900

RESUMO

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.


Assuntos
Diabetes Mellitus Experimental , Hexilresorcinol , Motilidade dos Espermatozoides , Testículo , Testosterona , Animais , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Ratos , Motilidade dos Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Hexilresorcinol/farmacologia , Hexilresorcinol/uso terapêutico , Apoptose/efeitos dos fármacos , Estreptozocina , Ratos Sprague-Dawley , Tamanho do Órgão/efeitos dos fármacos
6.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38397062

RESUMO

The ubiquitin/26S proteasome system is a crucial regulatory mechanism that governs various cellular processes in plants, including signal transduction, transcriptional regulation, and responses to biotic and abiotic stressors. Our study shows that the RING-H2-type E3 ubiquitin ligase, Arabidopsis Tóxicos en Levadura 2 (ATL2), is involved in response to fungal pathogen infection. Under normal growth conditions, the expression of the ATL2 gene is low, but it is rapidly and significantly induced by exogenous chitin. Additionally, ATL2 protein stability is markedly increased via chitin treatment, and its degradation is prolonged when 26S proteasomal function is inhibited. We found that an atl2 null mutant exhibited higher susceptibility to Alternaria brassicicola, while plants overexpressing ATL2 displayed increased resistance. We also observed that the hyphae of A. brassicicola were strongly stained with trypan blue staining, and the expression of A. brassicicola Cutinase A (AbCutA) was dramatically increased in atl2. In contrast, the hyphae were weakly stained, and AbCutA expression was significantly reduced in ATL2-overexpressing plants. Using bioinformatics, live-cell confocal imaging, and cell fractionation analysis, we revealed that ATL2 is localized to the plasma membrane. Further, it is demonstrated that the ATL2 protein possesses E3 ubiquitin ligase activity and found that cysteine 138 residue is critical for its function. Moreover, ATL2 is necessary to successfully defend against the A. brassicicola fungal pathogen. Altogether, our data suggest that ATL2 is a plasma membrane-integrated protein with RING-H2-type E3 ubiquitin ligase activity and is essential for the defense response against fungal pathogens in Arabidopsis.


Assuntos
Alternaria , Proteínas de Arabidopsis , Arabidopsis , Imunidade Vegetal , Alternaria/imunologia , Arabidopsis/imunologia , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Quitina/metabolismo , Regulação da Expressão Gênica de Plantas , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
7.
Sensors (Basel) ; 23(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299962

RESUMO

Reinforcement learning is one of the artificial intelligence methods that enable robots to judge and operate situations on their own by learning to perform tasks. Previous reinforcement learning research has mainly focused on tasks performed by individual robots; however, everyday tasks, such as balancing tables, often require cooperation between two individuals to avoid injury when moving. In this research, we propose a deep reinforcement learning-based technique for robots to perform a table-balancing task in cooperation with a human. The cooperative robot proposed in this paper recognizes human behavior to balance the table. This recognition is achieved by utilizing the robot's camera to take an image of the state of the table, then the table-balance action is performed afterward. Deep Q-network (DQN) is a deep reinforcement learning technology applied to cooperative robots. As a result of learning table balancing, on average, the cooperative robot showed a 90% optimal policy convergence rate in 20 runs of training with optimal hyperparameters applied to DQN-based techniques. In the H/W experiment, the trained DQN-based robot achieved an operation precision of 90%, thus verifying its excellent performance.


Assuntos
Inteligência Artificial , Robótica , Humanos , Robótica/métodos
8.
Sensors (Basel) ; 23(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37430625

RESUMO

The demand for deep learning frameworks capable of running in edge computing environments is rapidly increasing due to the exponential growth of data volume and the need for real-time processing. However, edge computing environments often have limited resources, necessitating the distribution of deep learning models. Distributing deep learning models can be challenging as it requires specifying the resource type for each process and ensuring that the models are lightweight without performance degradation. To address this issue, we propose the Microservice Deep-learning Edge Detection (MDED) framework, designed for easy deployment and distributed processing in edge computing environments. The MDED framework leverages Docker-based containers and Kubernetes orchestration to obtain a pedestrian-detection deep learning model with a speed of up to 19 FPS, satisfying the semi-real-time condition. The framework employs an ensemble of high-level feature-specific networks (HFN) and low-level feature-specific networks (LFN) trained on the MOT17Det dataset, achieving an accuracy improvement of up to AP50 and AP0.18 on MOT20Det data.

9.
Dev Dyn ; 251(12): 1982-2000, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36000457

RESUMO

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear encoded mitochondrial membrane protein that spans inner and outer membrane, and it has been shown to regulate mitochondrial dynamics and cholesterol metabolism. Since the mitochondrial functions have been implicated for osteogenic differentiation, a role of ATAD3A in skeletal development has been investigated. RESULTS: Mesenchyme-specific ATAD3 knockout mice displayed severe defects in skeletal development. Additionally, osteoblast-specific deletion of ATAD3 in mice caused significant reduction in bone mass, while cartilage-specific ATAD3 knockout mice did not show any significant phenotypes. Consistent with these in vivo findings, ATAD3A knockdown impaired mitochondrial morphology and function in calvarial pre-osteoblast cultures, which, in turn, suppressed osteogenic differentiation in vitro. CONCLUSIONS: The current findings suggest that ATAD3A plays a crucial role in mitochondria homeostasis, which is required for osteogenic differentiation during skeletal development.


Assuntos
Proteínas Mitocondriais , Osteogênese , Camundongos , Animais , Proteínas Mitocondriais/genética , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Osteogênese/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Osteoblastos/metabolismo , Camundongos Knockout
10.
Curr Psychol ; 42(12): 10186-10199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34566389

RESUMO

Because military special forces carry out dangerous missions, they are much more exposed to adversities and traumatic events compared to other occupational groups. According to Posttraumatic Growth theory, individuals tend to obtain positive growth through adversities. Moreover, a framework of Psychosocial Gains from Adversity argues not only individual changes but also social changes in the group to which the individual belongs are induced. Therefore, the present study aimed to explore the adverse experiences of special forces operatives and delineate the positive shift at an individual and social level via Consensual Qualitative Research (CQR). Eight individuals serving in special forces at the Korean Army, Navy and Air Force were interviewed using a semi-structured protocol. Four domains including 10 categories and 34 subcategories were identified: (a) Adverse experiences; (b) Personal change; (c) Social change; and (d) Attributes related to adverse experience. The findings and clinical implications are discussed in light of growth over facing adversities and interaction between personal and social factors.

11.
J Clin Microbiol ; 60(11): e0081222, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36286489

RESUMO

Filamentous fungi are a major cause of life-threatening infections in immunocompromised patients; thus, rapid and accurate identification is critical. Filamentous fungal identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been demonstrated with high sensitivity and reproducibility; however, its wider application has been limited in clinical laboratories because of practical challenges such as database availability or lack of standardization. In this study, we compared the performance of the Bruker Biotyper, ASTA MicroIDSys, and Vitek MS for 84 clinical filamentous fungal isolates. Moreover, the sensitivity of three independent sample preparation methods (direct, on plate, in tube) was compared. Bruker Biotyper identified 71.43% (60/84) of isolates correctly (species, genus, or complex/group level). ASTA MicroIDSys and Vitek MS showed accuracy rates of 70.24% (59/84) and 55.95% (47/84), respectively. We found that any difference in sensitivity may be attributed to the database of the systems. In addition, the "in tube" method showed the highest sensitivity among the three methods; however, there was no statistical difference among them. For the broader application of MALDI-TOF MS for filamentous fungal identification, further studies from multiple perspectives are required.


Assuntos
Serviços de Laboratório Clínico , Laboratórios Clínicos , Humanos , Reprodutibilidade dos Testes , Fungos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
12.
Plant Physiol ; 185(2): 405-423, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721904

RESUMO

In plants, root hairs undergo a highly polarized form of cell expansion called tip-growth, in which cell wall deposition is restricted to the root hair apex. In order to identify essential cellular components that might have been missed in earlier genetic screens, we identified conditional temperature-sensitive (ts) root hair mutants by ethyl methanesulfonate mutagenesis in Arabidopsis thaliana. Here, we describe one of these mutants, feronia-temperature sensitive (fer-ts). Mutant fer-ts seedlings were unaffected at normal temperatures (20°C), but failed to form root hairs at elevated temperatures (30°C). Map based-cloning and whole-genome sequencing revealed that fer-ts resulted from a G41S substitution in the extracellular domain of FERONIA (FER). A functional fluorescent fusion of FER containing the fer-ts mutation localized to plasma membranes, but was subject to enhanced protein turnover at elevated temperatures. While tip-growth was rapidly inhibited by addition of rapid alkalinization factor 1 (RALF1) peptides in both wild-type and fer-ts mutants at normal temperatures, root elongation of fer-ts seedlings was resistant to added RALF1 peptide at elevated temperatures. Additionally, at elevated temperatures fer-ts seedlings displayed altered reactive oxygen species (ROS) accumulation upon auxin treatment and phenocopied constitutive fer mutant responses to a variety of plant hormone treatments. Molecular modeling and sequence comparison with other Catharanthus roseus receptor-like kinase 1L (CrRLK1L) receptor family members revealed that the mutated glycine in fer-ts is highly conserved, but is not located within the recently characterized RALF23 and LORELI-LIKE-GLYCOPROTEIN 2 binding domains, perhaps suggesting that fer-ts phenotypes may not be directly due to loss of binding to RALF1 peptides.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Fosfotransferases/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Transdução de Sinais , Alelos , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/farmacologia , Membrana Celular/metabolismo , Parede Celular/metabolismo , Ácidos Indolacéticos/farmacologia , Mutação , Hormônios Peptídicos/farmacologia , Fenótipo , Fosfotransferases/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Domínios Proteicos , Espécies Reativas de Oxigênio/metabolismo , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/parasitologia , Temperatura
13.
Nature ; 529(7584): 54-8, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26738590

RESUMO

How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.

14.
Plant Cell Rep ; 41(7): 1549-1560, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35562569

RESUMO

KEY MESSAGE: Nuclear-localized Arabidopsis MYB3 functions as a transcriptional repressor for regulation of lignin and anthocyanin biosynthesis under high salt conditions. Salinity stress is a major factor which reduces plant growth and crop yield worldwide. To improve growth of crops in high salinity environments, plant responses to salinity stress must be tightly controlled. Here, to further understand the regulation of plant responses under high salinity conditions, the function of the MYB3 transcription factor was studied as a repressor to control accumulation of lignin and anthocyanin under salt stress conditions. Nuclear-localized MYB3 forms a homodimer. It is ubiquitously expressed, especially in vascular tissues, with expression highly induced by NaCl in tissues such as roots, leaves, stems, and flowers. myb3 mutant plants exhibited longer root growth in high NaCl conditions than wild-type plants. However, several NaCl responsive genes were not significantly altered in myb3 compared to wild-type. Interestingly, high accumulation of lignin and anthocyanin occurred in myb3 under NaCl treatment, as well as increased expression of genes involved in lignin and anthocyanin biosynthesis, such as phenylalanine ammonia lyase 1 (PAL1), cinnamate 4-hydroxylase (C4H), catechol-O-methyltransferase (COMT), 4-coumaric acid-CoA ligase (4CL3), dihydroflavonol reductase (DFR), and leucoanthocyanidin dioxygenase (LDOX). According to yeast two-hybrid screenings, various transcription factors, including anthocyanin regulators Transparent Testa 8 (TT8) and Enhancer of Glabra 3 (EGL3), were isolated as MYB3 interacting proteins. MYB3 was characterized as a transcriptional repressor, with its repressor domain located in the C-terminus. Overall, these results suggest that nuclear-localized MYB3 functions as a transcriptional repressor to control lignin and anthocyanin accumulation under salinity stress conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Antocianinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Regulação da Expressão Gênica de Plantas , Lignina/metabolismo , Estresse Salino/genética , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Sensors (Basel) ; 22(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35632233

RESUMO

The purpose of this paper is to study the recognition of ships and their structures to improve the safety of drone operations engaged in shore-to-ship drone delivery service. This study has developed a system that can distinguish between ships and their structures by using a convolutional neural network (CNN). First, the dataset of the Marine Traffic Management Net is described and CNN's object sensing based on the Detectron2 platform is discussed. There will also be a description of the experiment and performance. In addition, this study has been conducted based on actual drone delivery operations-the first air delivery service by drones in Korea.


Assuntos
Redes Neurais de Computação , Navios , República da Coreia
16.
Int J Mol Sci ; 23(18)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36142785

RESUMO

Inflammation is a critically important barrier found in innate immunity. However, severe and sustained inflammatory conditions are regarded as causes of many different serious diseases, such as cancer, atherosclerosis, and diabetes. Although numerous studies have addressed how inflammatory responses proceed and what kinds of proteins and cells are involved, the exact mechanism and protein components regulating inflammatory reactions are not fully understood. In this paper, to determine the regulatory role of mixed lineage kinase 3 (MLK3), which functions as mitogen-activated protein kinase kinase kinase (MAP3K) in cancer cells in inflammatory response to macrophages, we employed an overexpression strategy with MLK3 in HEK293 cells and used its inhibitor URMC-099 in lipopolysaccharide (LPS)-treated RAW264.7 cells. It was found that overexpressed MLK3 increased the mRNA expression of inflammatory genes (COX-2, IL-6, and TNF-α) via the activation of AP-1, according to a luciferase assay carried out with AP-1-Luc. Overexpression of MLK3 also induced phosphorylation of MAPKK (MEK1/2, MKK3/6, and MKK4/7), MAPK (ERK, p38, and JNK), and AP-1 subunits (c-Jun, c-Fos, and FRA-1). Phosphorylation of MLK3 was also observed in RAW264.7 cells stimulated by LPS, Pam3CSK, and poly(I:C). Finally, inhibition of MLK3 by URMC-099 reduced the expression of COX-2 and CCL-12, phosphorylation of c-Jun, luciferase activity mediated by AP-1, and phosphorylation of MAPK in LPS-treated RAW264.7 cells. Taken together, our findings strongly suggest that MLK3 plays a central role in controlling AP-1-mediated inflammatory responses in macrophages and that this enzyme can serve as a target molecule for treating AP-1-mediated inflammatory diseases.


Assuntos
Lipopolissacarídeos , Fator de Transcrição AP-1 , Animais , Ciclo-Oxigenase 2/metabolismo , Células HEK293 , Humanos , Inflamação , Interleucina-6 , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno , Células RAW 264.7 , RNA Mensageiro , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/genética , MAP Quinase Quinase Quinase 11 Ativada por Mitógeno
17.
Int J Mol Sci ; 24(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36613594

RESUMO

Silk sericin is a degumming product used by the silk industry. The degumming process can affect the protein structure and molecular weight of silk sericin. The present study examined how pretreatment with 4-hexylresorcinol (4HR) affects the biomedical properties of silk sericin. Before the degumming process, silkworm cocoons were treated with 4HR solution. The protein structure of the final degumming product was evaluated by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy. Untreated silk sericin (S) and silk sericin pretreated with 4HR (S+4HR) were added to RAW264.7 cells, and the expression of BMP-2 was determined. The bone-regenerating capacity of S+4HR was evaluated using the critical-sized rat calvarial defect model. Compared with S, S+4HR showed an increase in ß-sheet structures. Administration of S+4HR to RAW264.7 cells increased expression of BMP-2, mainly via the TLR-mediated signaling pathway. Bone volume, as measured by micro-computerized tomography, was significantly greater in the S+4HR group than in the S, gelatin alone, and unfilled control groups (p < 0.05 each). Expression of BMP-2 and runx2 in tissue specimens was significantly higher following treatment with S+4HR than with S (p < 0.05). Taken together, these findings show that 4HR pretreatment before the degumming process increased the ß-sheet structure of silk sericin, as well as inducing BMP-2 expression and bone regeneration ability.


Assuntos
Bombyx , Hexilresorcinol , Sericinas , Ratos , Animais , Sericinas/química , Hexilresorcinol/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Conformação Proteica em Folha beta , Seda/química , Bombyx/metabolismo
18.
Molecules ; 27(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35630718

RESUMO

Electric double-layer capacitors (EDLCs) are an excellent electrochemical energy storage system (ESS) because of their superior power density, faster charge-discharge ability, and longer cycle life compared to those of other EES systems. Activated carbons (ACs) have been mainly used as the electrode materials for EDLCs because of their high specific surface area, superior chemical stability, and low cost. Petroleum pitch (PP) is a graphitizable carbon that is a promising precursor for ACs because of its high carbon content, which is obtained as an abundant by-product during the distillation of petroleum. However, the processibility of PP is poor because of its stable structure. In this study, pre-oxidized PP-derived AC (OPP-AC) was prepared to investigate the effects of pre-oxidation on the electrochemical behaviors of PP. The specific surface area and pore size distribution of OPP-AC were lower and narrower, respectively, compared to the textural properties of untreated PP-derived AC (PP-AC). On the other hand, the specific capacitance of OPP-AC was 25% higher than that of PP-AC. These results revealed that pre-oxidation of PP induces a highly developed micropore structure of ACs, resulting in improved electrochemical performance.

19.
Plant J ; 103(3): 1205-1214, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32365248

RESUMO

LIKE HETEROCHROMATIN PROTEIN1 (LHP1) encodes the only plant homologue of the metazoan HETEROCHROMATIN PROTEIN1 (HP1) protein family. The LHP1 protein is necessary for proper epigenetic regulation of a range of developmental processes in plants. LHP1 is a transcriptional repressor of flowering-related genes, such as FLOWERING LOCUS T (FT), FLOWERING LOCUS C (FLC), AGAMOUS (AG) and APETALA 3 (AP3). We found that LHP1 interacts with importin α-1 (IMPα-1), importin α-2 (IMPα-2) and importin α-3 (IMPα-3) both in vitro and in vivo. A genetic approach revealed that triple mutation of impα-1, impα-2 and impα-3 resulted in Arabidopsis plants with a rapid flowering phenotype similar to that of plants with mutations in lhp1 due to the upregulation of FT expression. Nuclear targeting of LHP1 was severely impaired in the impα triple mutant, resulting in the de-repression of LHP1 target genes AG, AP3 and SHATTERPROOF 1 as well as FT. Therefore, the importin proteins IMPα-1, -2 and -3 are necessary for the nuclear import of LHP1.


Assuntos
Transporte Ativo do Núcleo Celular , Proteínas de Arabidopsis/metabolismo , Carioferinas/metabolismo , Fatores de Transcrição/metabolismo , alfa Carioferinas/metabolismo , Arabidopsis/metabolismo , Fotoperíodo
20.
Biochem Biophys Res Commun ; 571: 188-194, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34330063

RESUMO

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.


Assuntos
Proteínas de Homeodomínio/metabolismo , Osteoartrite/metabolismo , Fatores de Transcrição/metabolismo , Animais , Modelos Animais de Doenças , Proteínas de Homeodomínio/genética , Camundongos , Osteoartrite/patologia , Osteoartrite/cirurgia , Fatores de Transcrição/genética
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