RESUMEN
Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a central protein in necroptosis, but posttranslational processes that regulate RIP3 activity and stability remain poorly understood. Here, we identify pellino E3 ubiquitin protein ligase 1 (PELI1) as an E3 ligase that targets RIP3 for proteasome-dependent degradation. Phosphorylation of RIP3 on T182 leads to interaction with the forkhead-associated (FHA) domain of PELI1 and PELI1-mediated K48-linked polyubiquitylation of RIP3 on K363. This same phosphorylation event is also important for RIP3 kinase activity; thus, PELI1 preferentially targets kinase-active RIP3 for degradation. PELI1-mediated RIP3 degradation effectively prevents cell death triggered by RIP3 hyperactivation. Importantly, upregulated RIP3 expression in keratinocytes from toxic epidermal necrolysis (TEN) patients is correlated with low expression of PELI1, suggesting that loss of PELI1 may play a role in the pathogenesis of TEN. We propose that PELI1 may function to control inadvertent activation of RIP3, thus preventing aberrant cell death and maintaining cellular homeostasis.
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Queratinocitos/enzimología , Proteínas Nucleares/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Síndrome de Stevens-Johnson/enzimología , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Muerte Celular , Fibroblastos/enzimología , Fibroblastos/patología , Células HEK293 , Células HT29 , Células HeLa , Humanos , Queratinocitos/patología , Ratones , Proteínas Nucleares/genética , Fosforilación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Proteolisis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Transducción de Señal , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/patología , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
AIMS: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. METHODS: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. RESULTS: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1ß inhibition. CONCLUSIONS: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Sorafenib/farmacología , Sorafenib/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Inflamasomas/metabolismo , Inflamasomas/farmacología , Fosforilación , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sistema de Señalización de MAP Quinasas , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Proliferación Celular , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/farmacología , Sirtuinas/genética , Sirtuinas/metabolismo , Sirtuinas/farmacologíaRESUMEN
The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , MicroARNs/metabolismo , Procesamiento Postranscripcional del ARN/fisiología , Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/fisiología , Hojas de la Planta/metabolismo , Proteínas de Unión al ARN/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
ZAP-70 is required for the initiation of T cell receptor (TCR) signaling, and Ssu72 is a phosphatase that regulates RNA polymerase II activity in the nucleus. However, the mechanism by which ZAP-70 regulates the fine-tuning of TCR signaling remains elusive. Here, we found that Ssu72 contributed to the fine-tuning of TCR signaling by acting as tyrosine phosphatase for ZAP-70. Affinity purification-mass spectrometry and an in vitro assay demonstrated specific interaction between Ssu72 and ZAP-70 in T cells. Upon TCR stimulation, Ssu72-deficient T cells increased the phosphorylation of ZAP-70 and downstream molecules and exhibited hyperresponsiveness, which was restored by reducing ZAP-70 phosphorylation. In vitro assay demonstrated that recombinant Ssu72 reduced tyrosine phosphorylation of ZAP-70 via phosphatase activity. Cd4-CreSsu72fl/fl mice showed a defect in the thymic development of invariant natural killer T cells and reductions in CD4+ and CD8+ T cell numbers in the periphery but more CD44hiCD62Llo memory T cells and fewer CD44loCD62Lhi naïve T cells, compared with wild-type mice. Furthermore, Cd4-CreSsu72fl/fl mice developed spontaneous inflammation at 6 mo. In conclusion, Ssu72 phosphatase regulates the fine-tuning of TCR signaling by binding to ZAP-70 and regulating its tyrosine phosphorylation, thereby preventing spontaneous inflammation.
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Linfocitos T CD8-positivos/inmunología , Inflamación/prevención & control , Células T de Memoria/inmunología , Fosfoproteínas Fosfatasas/fisiología , Receptores de Antígenos de Linfocitos T/metabolismo , Proteína Tirosina Quinasa ZAP-70/metabolismo , Animales , Comunicación Celular , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Proteína Tirosina Quinasa ZAP-70/genéticaRESUMEN
Stretchable energy storage devices receive a considerable attention at present due to their growing demand for powering wearable electronics. A vital component in stretchable energy storage devices is its electrode which should endure a large and repeated number of mechanical deformations during its prolonged use. It is crucial to develop a technology to fabricate highly deformable electrode in an easy and an economic manner. Here, the fabrication of stretchable electrode substrates using 3D-printing technology is reported. The ink for fabricating it contains a mixture of sacrificial sugar particles and polydimethylsiloxane resin which solidifies upon thermal curing. The printed stretchable substrate attains a porous structure after leaching the sugar particles in water. The resulting printed porous stretchable substrates are then utilized as electrodes for Li-ion batteries (LIBs) after loading them with electrode materials. The batteries with stretchable electrodes exhibit a decent electrochemical performance comparable to that of the conventional electrodes. The stretchable electrodes also exhibit a stable electrochemical performance under various mechanical deformations and even after several hundreds of stretch/release cycles. This work provides a feasible route for constructing LIBs with high stretchability and enhanced electrochemical performance thereby providing a platform for realizing stretchable batteries for next generation wearable electronics.
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Suministros de Energía Eléctrica , Siliconas , Iones , Electrodos , Litio/química , Azúcares , Impresión TridimensionalRESUMEN
Pellino-1 plays a crucial role in cellular proliferation and regulates inflammatory processes. This study investigated Pellino-1 expression patterns and their relationship with CD4+ T-cell subsets in psoriasis patients. Group 1 comprised primarily biopsied psoriasis lesions from 378 patients, multiplex-immunostained for Pellino-1, CD4 and representative T helper (Th) cells (T-bet [Th1], GATA3 [Th2], and RORγt [Th17] and regulatory T cell [FoxP3] markers). Ki-67 labeling was evaluated in the epidermis. Group 2 comprised 43 Pellino-1-positive cases immunostained for Pellino-1 in both lesion and non-lesion skin biopsy samples. Five normal skin biopsies served as controls. Among 378 psoriasis cases, 293 (77.5%) were positive for Pellino-1 in the epidermis. Pellino-1-positivity was higher in psoriasis lesions than in non-lesions and normal skin (52.55% vs. 40.43% vs. 3.48%, p < 0.001; H-score, 72.08 vs. 47.55 vs. 4.40, p < 0.001, respectively). Pellino-1-positive cases also had a significantly higher Ki-67 labeling index (p < 0.001). Epidermal Pellino1-positivity was significantly associated with higher RORγt+ (p = 0.001) and FoxP3+ (p < 0.001) CD4+ T cell ratios but not T-bet+ and GATA3+ CD4+ T cell ratios. Among the CD4+ Pellino-1+ T-cell subsets, the CD4+ Pellino-1+ RORγt+ ratio was significantly associated with epidermal Pellinio-1 expression (p < 0.001). Pellino-1 expression is thus increased in psoriasis lesions and associated with increased epidermal proliferation and CD4+ T-cell subset infiltration, especially Th17 cells. This suggests that Pellino-1 could be a therapeutic target that simultaneously regulates psoriasis epidermal proliferation and immune interactions.
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Psoriasis , Células Th17 , Humanos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Antígeno Ki-67/metabolismo , Epidermis/metabolismo , Psoriasis/tratamiento farmacológico , Proliferación Celular , Factores de Transcripción Forkhead/metabolismoRESUMEN
Skin-based wearable devices have gained significant attention due to advancements in soft materials and thin-film technologies. Nevertheless, traditional wearable electronics often entail expensive and intricate manufacturing processes and rely on metal-based substrates that are susceptible to corrosion and lack flexibility. In response to these challenges, this paper has emerged with an alternative substrate for wearable electrodes due to its cost-effectiveness and scalability in manufacturing. Paper-based electrodes offer an attractive solution with their inherent properties of high breathability, flexibility, biocompatibility, and tunability. In this study, we introduce carbon nanotube-based paper composites (CPC) electrodes designed for the continuous detection of biopotential signals, such as electrooculography (EOG), electrocardiogram (ECG), and electroencephalogram (EEG). To prevent direct skin contact with carbon nanotubes, we apply various packaging materials, including polydimethylsiloxane (PDMS), Eco-flex, polyimide (PI), and polyurethane (PU). We conduct a comparative analysis of their signal-to-noise ratios in comparison to conventional gel electrodes. Our system demonstrates real-time biopotential monitoring for continuous health tracking, utilizing CPC in conjunction with a portable data acquisition system. The collected data are analyzed to provide accurate heart rates, respiratory rates, and heart rate variability metrics. Additionally, we explore the feasibility using CPC for sleep monitoring by collecting EEG signals.
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Nanotubos de Carbono , Dispositivos Electrónicos Vestibles , Nanotubos de Carbono/química , Piel , Electrodos , Sueño , ElectrocardiografíaRESUMEN
Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events in which DNA damage is recognized, DNA repair factors are recruited to the site of damage, the lesion is repaired, and cellular responses associated with the damage are processed. In cancer, DDR is commonly dysregulated, and the enzymes associated with DDR are prone to changes in ubiquitination. Additionally, cellular metabolism, especially glycolysis, is upregulated in cancer cells, and enzymes in this metabolic pathway are modulated by ubiquitination. The ubiquitin-proteasome system (UPS), particularly E3 ligases, act as a bridge between cellular metabolism and DDR since they regulate the enzymes associated with the two processes. Hence, the E3 ligases with high substrate specificity are considered potential therapeutic targets for treating cancer. A number of small molecule inhibitors designed to target different components of the UPS have been developed, and several have been tested in clinical trials for human use. In this review, we discuss the role of ubiquitination on overall cellular metabolism and DDR and confirm the link between them through the E3 ligases NEDD4, APC/CCDH1, FBXW7, and Pellino1. In addition, we present an overview of the clinically important small molecule inhibitors and implications for their practical use.
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Neoplasias , Humanos , Ubiquitinación , Neoplasias/patología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Daño del ADN , Ubiquitina/metabolismo , Reparación del ADNRESUMEN
Ferulic acid and related hydroxycinnamic acids, used as antioxidants and preservatives in the food, cosmetic, pharmaceutical and biotechnology industries, are among the most abundant phenolic compounds present in plant biomass. Identification of novel compounds that can produce ferulic acid and hydroxycinnamic acids, that are safe and can be mass-produced, is critical for the sustainability of these industries. In this study, we aimed to obtain and characterize a feruloyl esterase (LaFae) from Lactobacillus acidophilus. Our results demonstrated that LaFae reacts with ethyl ferulate and can be used to effectively produce ferulic acid from wheat bran, rice bran and corn stalks. In addition, xylanase supplementation was found to enhance LaFae enzymatic hydrolysis, thereby augmenting ferulic acid production. To further investigate the active site configuration of LaFae, crystal structures of unliganded and ethyl ferulate-bound LaFae were determined at 2.3 and 2.19 Å resolutions, respectively. Structural analysis shows that a Phe34 residue, located at the active site entrance, acts as a gatekeeper residue and controls substrate binding. Mutating this Phe34 to Ala produced an approximately 1.6-fold increase in LaFae activity against p-nitrophenyl butyrate. Our results highlight the considerable application potential of LaFae to produce ferulic acid from plant biomass and agricultural by-products.
Asunto(s)
Ácidos Cumáricos , Lactobacillus acidophilus , Ácidos Cumáricos/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Plantas/metabolismoRESUMEN
To improve the poor survival rate of lung cancer patients, we investigated the role of HDGF-related protein 3 (HRP-3) as a potential biomarker for lung cancer. The expression of endogenous HRP-3 in human lung cancer tissues and xenograft tumor models is indicative of its clinical relevance in lung cancer. Additionally, we demonstrated that HRP-3 directly binds to the E2F1 promoter on chromatin. Interestingly, HRP-3 depletion in A549 cells impedes the binding of HRP-3 to the E2F1 promoter; this in turn hampers the interaction between Histone H3/H4 and HDAC1/2 on the E2F1 promoter, while concomitantly inducing Histone H3/H4 acetylation around the E2F1 promoter. The enhanced Histone H3/H4 acetylation on the E2F1 promoter through HRP-3 depletion increases the transcription level of E2F1. Furthermore, the increased E2F1 transcription levels lead to the enhanced transcription of Cyclin E, known as the E2F1-responsive gene, thus inducing S-phase accumulation. Therefore, our study provides evidence for the utility of HRP-3 as a biomarker for the prognosis and treatment of lung cancer. Furthermore, we delineated the capacity of HRP-3 to regulate the E2F1 transcription level via histone deacetylation.
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Biomarcadores de Tumor/metabolismo , Ciclina E/metabolismo , Factor de Transcripción E2F1/genética , Histona Desacetilasas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/patología , Células A549 , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Trasplante de Neoplasias , Regiones Promotoras Genéticas , Transducción de SeñalRESUMEN
We investigate the enhancement in sensitivity when measuring a weak force through the optical response of an optomechanical oscillator driven by squeezed light. In the context of a quantum sensor based on cavity-optomechanics, the sensitivity scaling measured by the quantum Fisher information for a squeezed vacuum state pump is compared to that for a coherent state pump. We show that squeezed state inputs can produce noise levels below the standard quantum limit and even the Heisenberg limit in given regimes. This study shows that new pathways can be opened for enhanced quantum sensing with optomechanical systems conducive to measuring various physical quantities such as gravitational force, acceleration, and acoustics.
RESUMEN
BACKGROUND: Fine-tuning of immune receptor signaling is critical for the development and functioning of immune cells. Moreover, GM-CSF receptor (GM-CSFR) signaling plays an essential role in the development of certain myeloid lineage cells, including alveolar macrophages (AMs). However, the significance of fine-tuning of GM-CSFR signaling in AMs and its relevance in allergic inflammation have not been reported. OBJECTIVE: Our aim was to explore whether phosphatase Ssu72, originally identified as a regulator of RNA polymerase II activity, regulates AM development and allergic airway inflammation by regulating GM-CSF signaling. METHODS: To address these issues, we generated LysM-CreSsu72fl/fl and Cd11c-CreSsu72fl/fl mice and used ovalbumin- or house dust mite-induced allergic asthma models. RESULTS: Following GM-CSF stimulation, Ssu72 directly bound to the GM-CSFR ß-chain in AMs, preventing phosphorylation. Consistently, mature Ssu72-deficient AMs showed higher phosphorylation of the GM-CSFR ß-chain and downstream molecules, which resulted in greater dysregulation of cell cycle, cell death, cell turnover, mitochondria-related metabolism, and LPS responsiveness in AMs than in mature wild-type AMs. The dysregulation was restored by using a Janus kinase 2 inhibitor, which reduced GM-CSFR ß-chain phosphorylation. LysM-CreSsu72fl/fl mice exhibited deficits in development and maturation of AMs, which were also seen postnatally in Cd11c-CreSsu72fl/fl mice. Furthermore, LysM-CreSsu72fl/fl mice were less responsive to ovalbumin- or house dust mite-induced allergic asthma models than the control mice were; however, their responsiveness was restored by adoptive transfer of JAK2 inhibitor-pretreated mature Ssu72-deficient AMs. CONCLUSION: Our results demonstrate that Ssu72 fine-tunes GM-CSFR signaling by both binding to and reducing phosphorylation of GM-CSFR ß-chain, thereby regulating the development, maturation, and mitochondrial functions of AMs and allergic airway inflammation.
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Hipersensibilidad/inmunología , Macrófagos Alveolares/fisiología , Fosfoproteínas Fosfatasas/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Hipersensibilidad Respiratoria/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Antígeno CD11c/metabolismo , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina/inmunología , Fosfoproteínas Fosfatasas/genética , Pyroglyphidae , Transducción de SeñalRESUMEN
Recent studies have reported that small double-strand RNAs (dsRNAs) can activate endogenous genes via an RNA-based promoter targeting mechanism termed RNA activation (RNAa). In the present study, we showed that dsVDUP1-834, a novel small activating RNA (saRNA) targeting promoter of vitamin D3 up-regulated protein 1 (VDUP1) gene, up-regulated expression of VDUP1 at both mRNA and protein levels in A549 lung cancer cells. We also demonstrated that dsVDUP1-834 inhibited cell proliferation in A549 lung cancer cells. Further studies showed that dsVDUP1-834 induced cell-cycle arrest by increasing p27 and p53 and decreasing cyclin A and cyclin B1. In addition, knockdown of VDUP1 abrogated dsVDUP1-834-induced up-regulation of VDUP1 gene expression and related effects. The activation of VDUP1 by dsVDUP1-834 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 3 (H3ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) at the target site of VDUP1 promoter. Moreover, the enrichment of Ago2 was detected at the dsVDUP1-834 target site, and Ago2 knockdown significantly suppressed dsVDUP1-834-mediated inhibition of cell proliferation and modulation of cell-cycle regulators. Taken together, the results presented in this report demonstrate that dsVDUP1-834 induces VDUP1 gene expression by epigenetic changes, resulting in cell growth inhibition and cell-cycle arrest. Our results suggest that targeted induction of VDUP1 by dsVDUP1-834 might be a promising therapeutic strategy for the treatment of lung cancer.
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Proteínas Portadoras/metabolismo , Neoplasias Pulmonares , Histonas/metabolismo , Humanos , Neoplasias Pulmonares/genética , Lisina/genética , ARN BicatenarioRESUMEN
Histone H2AX undergoes a phosphorylation switch from pTyr142 (H2AX-pY142) to pSer139 (γH2AX) in the DNA damage response (DDR); however, the functional role of H2AX-pY142 remains elusive. Here, we report a new layer of regulation involving transcription-coupled H2AX-pY142 in the DDR. We found that constitutive H2AX-pY142 generated by Williams-Beuren syndrome transcription factor (WSTF) interacts with RNA polymerase II (RNAPII) and is associated with RNAPII-mediated active transcription in proliferating cells. Also, removal of pre-existing H2AX-pY142 by ATM-dependent EYA1/3 phosphatases disrupts this association and requires for transcriptional silencing at transcribed active damage sites. The following recovery of H2AX-pY142 via translocation of WSTF to DNA lesions facilitates transcription-coupled homologous recombination (TC-HR) in the G1 phase, whereby RAD51 loading, but not RPA32, utilizes RNAPII-dependent active RNA transcripts as donor templates. We propose that the WSTF-H2AX-RNAPII axis regulates transcription and TC-HR repair to maintain genome integrity.
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Histonas/metabolismo , Reparación del ADN por Recombinación , Factores de Transcripción/metabolismo , Transcripción Genética , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Fase G1/genética , Células HEK293 , Células HeLa , Histonas/química , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación , Proteínas Tirosina Fosfatasas/metabolismo , ARN Polimerasa II/metabolismo , Tirosina/metabolismoRESUMEN
BACKGROUND: The present study investigated associations between defense mechanisms and life satisfaction among North Korean refugees living in South Korea. METHODS: A total of 178 North Korean refugees completed the Korean version of the Defense Style Questionnaire, a revised version of the Ways of Thinking of North Korean Defectors scale, the Center for Epidemiologic Studies-Depression Scale, and the State-Trait Anxiety Inventory. Multiple stepwise regression analysis was performed to investigate the defense mechanisms associated with North Korean refugees' life satisfaction in South Korea. RESULTS: Among defense mechanisms, denial most strongly predicted higher overall and economic satisfaction among North Korean refugees living in South Korea (ß = 0.145, p < 0.01; ß = 0.137, p = 0.03, respectively) after controlling for age, gender, anxiety, depression, and number of traumatic events experienced. Furthermore, resignation predicted lower overall (ß = -0.206, p < 0.001) and economic satisfaction (ß = -0.134, p = 0.02). However, the association between resignation and life satisfaction was not significant after controlling for depression, anxiety, and number of traumatic events experienced. CONCLUSIONS: Specific defense mechanisms such as high denial and low resignation were associated with life satisfaction in South Korea among North Korean refugees. Our findings suggest that refugees' psychological defense mechanisms may affect their satisfactory resettlement.
RESUMEN
More than 70% of eukaryotic proteins are regulated by phosphorylation. However, the mechanism of dephosphorylation that counteracts phosphorylation is less studied. Phosphatases are classified into 104 distinct groups based on substrate-specific features and the sequence homologies in their catalytic domains. Among them, dual-specificity phosphatases (DUSPs) that dephosphorylate both phosphoserine/threonine and phosphotyrosine are important for cellular homeostasis. Ssu72 is a newly studied phosphatase with dual specificity that can dephosphorylate both phosphoserine/threonine and phosphotyrosine. It is important for cell-growth signaling, metabolism, and immune activation. Ssu72 was initially identified as a phosphatase for the Ser5 and Ser7 residues of the C-terminal domain of RNA polymerase II. It prefers the cis configuration of the serine-proline motif within its substrate and regulates Pin1, different from other phosphatases. It has recently been reported that Ssu72 can regulate sister chromatid cohesion and the separation of duplicated chromosomes during the cell cycle. Furthermore, Ssu72 appears to be involved in the regulation of T cell receptor signaling, telomere regulation, and even hepatocyte homeostasis in response to a variety of stress and damage signals. In this review, we aim to summarize various functions of the Ssu72 phosphatase, their implications in diseases, and potential therapeutic indications.
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Fosfoproteínas Fosfatasas/metabolismo , ARN Polimerasa II/metabolismo , Transducción de Señal , Animales , Cromátides/genética , Cromátides/metabolismo , Cromosomas Humanos/genética , Cromosomas Humanos/metabolismo , Humanos , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Fosfoproteínas Fosfatasas/genética , Dominios Proteicos , ARN Polimerasa II/genética , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
Pluripotent stem cell-derived mesenchymal progenitor cells (PSC-MPCs) are primarily derived through two main methods: three-dimensional (3D) embryoid body-platform (EB formation) and the 2D direct differentiation method. We recently established somatic cell nuclear transfer (SCNT)-PSC lines and showed their stemness. In the present study, we produced SCNT-PSC-MPCs using a novel direct differentiation method, and the characteristics, gene expression, and genetic stability of these MPCs were compared with those derived through EB formation. The recovery and purification of SCNT-PSC-Direct-MPCs were significantly accelerated compared to those of the SCNT-PSC-EB-MPCs, but both types of MPCs expressed typical surface markers and exhibited similar proliferation and differentiation potentials. Additionally, the analysis of gene expression patterns using microarrays showed very similar patterns. Moreover, array CGH analysis showed that both SCNT-PSC-Direct-MPCs and SCNT-PSC-EB-MPCs exhibited no significant differences in copy number variation (CNV) or single-nucleotide polymorphism (SNP) frequency. These results indicate that SCNT-PSC-Direct-MPCs exhibited high genetic stability even after rapid differentiation into MPCs, and the rate at which directly derived MPCs reached a sufficient number was higher than that of MPCs derived through the EB method. Therefore, we suggest that the direct method of differentiating MPCs from SCNT-PSCs can improve the efficacy of SCNT-PSCs applied to allogeneic transplantation.
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Inestabilidad Genómica , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Técnicas de Transferencia Nuclear/normas , Diferenciación Celular , Línea Celular , Células Cultivadas , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Mesenquimatosas/citología , Polimorfismo GenéticoRESUMEN
The RidA subfamily proteins catalyze the deamination reaction of enamine/imine intermediates, which are metabolites of amino acids such as threonine and serine. Numerous structural and functional studies have been conducted on RidA isolated from mesophiles and thermophiles. However, little is known about the structure of the RidA proteins isolated from psychrophiles. In the present study, we elucidated the crystal structure of RidA from the Antarctic bacterium Psychrobacter sp. PAMC 21119 (Pp-RidA) at 1.6 Å resolution to identify the structural properties contributing to cold-adaptability. Although the overall structure of Pp-RidA is similar to those of its homologues, it exhibits specific structural arrangements of a loop positioned near the active site, which is assumed to play a role in covering the active site of catalysis. In addition, the surface electrostatic potential of Pp-RidA suggested that it exhibits stronger electrostatic distribution relative to its homologues. Our results provide novel insights into the key determinants of cold-adaptability.
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Aminohidrolasas/química , Proteínas Bacterianas/química , Psychrobacter/química , Aclimatación , Secuencia de Aminoácidos , Aminohidrolasas/metabolismo , Proteínas Bacterianas/metabolismo , Dominio Catalítico , Respuesta al Choque por Frío , Cristalografía por Rayos X , Desaminación , Iminas/metabolismo , Conformación Proteica , Psychrobacter/enzimología , Psychrobacter/fisiologíaRESUMEN
Scytonemin is a yellow-green ultraviolet sunscreen pigment present in different genera of aquatic and terrestrial blue-green algae, including marine cyanobacteria. In the present study, the anti-inflammatory activities of scytonemin were evaluated in vitro and in vivo. Topical application of scytonemin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear swelling in BALB/c mice. The expression of tumor necrosis factor-a (TNF-a) and inducible nitric oxide synthase (iNOS) was also suppressed by scytonemin treatment in the TPA-treated ear of BALB/c mice. In addition, scytonemin inhibited lipopolysaccharide (LPS)-induced production of TNF-a and nitric oxide (NO) in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expressions of TNF-a and iNOS were also suppressed by scytonemin in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced NF-kB activity was significantly suppressed by scytonemin treatment in RAW 264.7 cells. Our results also showed that the degradation of IkBa and nuclear translocation of the p65 subunit were blocked by scytonemin in LPS-stimulated RAW 264.7 cells. Collectively, these results suggest that scytonemin inhibits skin inflammation by blocking the expression of inflammatory mediators, and the anti-inflammatory effect of scytonemin is mediated, at least in part, by down-regulation of NF-kB activity. Our results also suggest that scytonemin might be used as a multi-function skin care ingredient for UV protection and anti-inflammation.
Asunto(s)
Antiinflamatorios/farmacología , Indoles/farmacología , Fenoles/farmacología , Protectores Solares/farmacología , Animales , Lipopolisacáridos , Ratones , Ratones Endogámicos BALB C , Inhibidor NF-kappaB alfa , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Acetato de Tetradecanoilforbol/análogos & derivados , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: This study aimed to compare the effects of diets with and without supplements of methionine/lysine (met/lys) and methionine/α-tocopherol (met/α-tocopherol) on the performance, carcass traits and meat quality of Hanwoo steers. METHODS: A total of 21 Hanwoo steers were divided into three different groups. Each group consisted of 7 animals that received different dietary treatments for 120 days as follows: a control (C) diet composed of a basal diet with 74% total digestible nutrient and 12% crude protein; treatment 1 (T1) composed of a basal diet enriched with methionine 69%+lysine 31%; and treatment (T2) composed of a basal diet enriched with methionine 84.65%+α-tocopherol 15.35%. Daily supplementation was given using the top-dressing method (20 g/animal). RESULTS: The met/lys groups yielded a longissimus lumborum with increased water holding capacity (p<0.01) and lower shear force value (p<0.05). Dietary met/lys did not have an adverse effect on the animal performance and carcass traits. Instead, these supplements contributed significantly to the higher protein content compared to the control diet (p<0.05). Myristic acid (C14:0) was the only fatty acid affected by the supplementation. While the met/α-tocopherol group led to significantly higher protein and oxymyoglobin contents during storage (p<0.05). It also contributed significantly to the lower shear force value and 2-thiobarbituric acid reactive substances score during storage (p<0.05) compared to the control and treatment 1 since the initial storage day. The met/α-tocopherol diet also yielded meat with a redder color (p<0.05) after 3 days of storage. However, it did not significantly contribute to the fatty acid profiles of Hanwoo steers. CONCLUSION: Met/lys supplementation resulted in higher protein scores, water holding capacity and lower shear force scores. While met/α-tocopherol supplementation contributes to the production of redder meat, reduces lipid oxidation, production of more tender meat and increases the content of protein and oxymyoglobin percentage.