RESUMEN
BACKGROUND: The social representation theory states that individual differences in reciprocity decisions are composed of a stable central core (i.e., reciprocity propensity, RP) and a contextual-dependent periphery (i.e., sensitivity to the framing effect; SFE, the effect by how the decision is presented). However, the neural underpinnings that explain RP and SFE are still unknown. METHOD: Here, we employed prediction and lesion models to decode resting-state functional connectivity (RSFC) of RP and SFE for reciprocity decisions of healthy volunteers who underwent RS functional magnetic resonance imaging and completed one-shot trust (give frame) and distrust (take frame) games as trustees. RESULTS: Regarding the central core, reciprocity rates were positively associated between the give and take frame. Neuroimaging results showed that inter-network RSFC between the default-mode network (DMN; associated with mentalizing) and cingulo-opercular network (associated with cognitive control) contributed to the prediction of reciprocity under both frames. Regarding the periphery, behavioral results demonstrated a significant framing effect-people reciprocated more in the give than in the take frame. Our neuroimaging results revealed that intra-network RSFC of DMN (associated with mentalizing) contributed dominantly to the prediction of SFE. CONCLUSION: Our findings provide evidence for distinct neural mechanisms of RP and SFE in reciprocity decisions.
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Conectoma , Humanos , Imagen por Resonancia Magnética/métodos , Confianza , Neuroimagen , Vías Nerviosas/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. METHOD: We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. RESULTS: We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. CONCLUSION: These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.
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Apatía , Humanos , Vías Nerviosas/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Encéfalo , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodosRESUMEN
AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.
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Trampas Extracelulares , Encía , Líquido del Surco Gingival , Queratinocitos , Periodontitis , Humanos , Trampas Extracelulares/metabolismo , Encía/metabolismo , Líquido del Surco Gingival/química , Queratinocitos/metabolismo , Periodontitis/metabolismo , Periodontitis/inmunología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Factor 4 Similar a Kruppel , Saliva/metabolismo , Saliva/química , Calcio/metabolismo , Calcio/análisis , Estudios de Casos y Controles , Epitelio , Queratinas/metabolismo , Cadherinas/metabolismo , Cadherinas/análisisRESUMEN
The present study combined a novel hypothetical investment game with functional magnetic resonance imaging to examine how moral conflict biases our real decision preference when it is not obvious or explicitly presented. Investment projects were chosen based on their prior subjective morality ratings to fit into 2 categories: a high level of moral conflict (HMC) or a low level of moral conflict (LMC). Participants were instructed to invest high or low amounts of capital into different projects. Behavioral and neural responses during decision making were recorded and compared. Behaviorally, we observed a significant decision bias such that investments were lower for HMC projects than for LMC projects. At the neural level, we found that moral conflict-related activity in the anterior cingulate cortex (ACC) was higher in the HMC condition than in the LMC condition and that reward-related activity in bilateral striatum was lower. Dynamic causal modeling further suggested that the moral conflict detected in the ACC influenced final decisions by modulating the representation of subjective value through the ACC's connection to the reward system.
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Mapeo Encefálico , Giro del Cíngulo , Mapeo Encefálico/métodos , Toma de Decisiones/fisiología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Principios Morales , RecompensaRESUMEN
As an important cognitive bias, the framing effect shows that our decision preferences are sensitive to the verbal description (i.e., frame) of options. This study focuses on the neural underpinnings of the social framing effect, which is based on decision-making regarding other people. A novel paradigm was used in which participants made a trade-off between economic benefits and the feelings of others. This decision was described as either a "harm" to, or "not helping," other persons in two conditions (Harm frame vs Help frame). Both human males and females were recruited. Participants behaved more prosocially for Harm frame compared with Help frame, resulting in a significant social framing effect. Using functional magnetic resonance imaging, Experiment 1 showed that the social framing effect was associated with stronger activation in the temporoparietal junction (TPJ), especially its right part. The functional connectivity between the right TPJ (rTPJ) and medial prefrontal cortex predicted the social framing effect on the group level. In Experiment 2, we used transcranial direct current stimulation to modulate the activity of the rTPJ and found that the social framing effect became more prominent under anodal (excitatory) stimulation, while the nonsocial framing effect elicited by the economic gain/loss gambling frame remained unaffected. The rTPJ results might be associated with moral conflicts modulated by the social consequences of an action or different levels of mentalizing with others under different frame conditions, but alternative interpretations are also worth noting. These findings could help elucidate the psychological mechanisms of the social framing effect.SIGNIFICANCE STATEMENT Previous studies have suggested that the framing effect is generated from an interaction between the amygdala and anterior cingulate cortex. This opinion, however, is based on findings from nonsocial framing tasks. Recent research has highlighted the importance of distinguishing between the social and nonsocial framing effects. The current study focuses on the social framing effect and finds out that the temporoparietal junction and its functional connectivity with the medial prefrontal cortex play a significant role. Additionally, modulating the activity of this region leads to changes in social (but not nonsocial) framing effect. Broadly speaking, these findings help understand the difference in neural mechanisms between social and nonsocial decision-making. Meanwhile, they might be illuminating to promote helping behavior in society.
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Amígdala del Cerebelo/fisiología , Toma de Decisiones/fisiología , Imagen por Resonancia Magnética/métodos , Corteza Prefrontal/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Amígdala del Cerebelo/diagnóstico por imagen , Femenino , Humanos , Masculino , Corteza Prefrontal/diagnóstico por imagen , Adulto JovenRESUMEN
Forkhead box R2 (FOXR2), a new member of the FOX family, is involved in a wide range of biological processes such as embryogenesis, differentiation, transformation and metabolic homeostasis. Recently, FOXR2 has been reported to be aberrantly expressed in a variety of cancers and correlated with cancer development. However, the specific role of FOXR2 in thyroid cancer (TC) remains unclear. In this study, we showed that FOXR2 was highly expressed in TC tissues and cell lines. Moreover, down-regulation of FOXR2 inhibited hypoxia-induced reactive oxygen species (ROS) production and migration/invasion of TC cells. We also found that the hedgehog pathway was responsible for the partial mechanisms underlying the inhibitory effect. Taken together, these findings indicated that down-regulation of FOXR2 inhibits hypoxia-driven ROS-induced migration and invasion of TC cells via regulation of the hedgehog pathway. Thus, FOXR2 may hold great potential for TC treatment.
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Movimiento Celular , Factores de Transcripción Forkhead/metabolismo , Proteínas Hedgehog/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Tiroides/metabolismo , Línea Celular Tumoral , Regulación hacia Abajo , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Hedgehog/genética , Humanos , Invasividad Neoplásica , Transducción de Señal , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Hipoxia TumoralRESUMEN
Moral contagion is a phenomenon in which individuals or objects take on the moral essence of the people who are associated with them. Previous studies have found that individuals value objects associated with moral and likable people more than those associated with immoral and dislikable people. However, the neural mechanisms underlying this "moral contagion effect" have not yet been explored. In the present study, we combined a novel "Second-hand Goods Pricing" paradigm with functional magnetic resonance imaging to (a) confirm the existence of the moral contagion effect on the hypothetical economic valuation of objects and (b) determine the neural substrates underlying it. Participants were shown second-hand goods, information regarding the moral valence of the previous owner, and an initial price assigned to the object by computer. The participants were then asked to adjust the initial price to one they deemed most reasonable. Behaviorally, we found a significant devaluation effect for immoral owners and a weaker reverse effect for moral owners. Imaging data showed that the devaluation effect was primarily driven by neural responses in the dorsal striatum (mainly the caudate nucleus) that were triggered by high initial prices assigned to the "contaminated" objects. Dynamic causal modeling revealed that the high initial price assigned to "contaminated" objects led to increased effective connectivity from the caudate nucleus to the ventromedial prefrontal cortex-the brain area that integrates values during decision making.
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Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Economía del Comportamiento , Juicio , Imagen por Resonancia Magnética/métodos , Principios Morales , Adulto , Encéfalo/fisiología , Toma de Decisiones/fisiología , Femenino , Humanos , Juicio/fisiología , Masculino , Estimulación Luminosa/métodos , Desempeño Psicomotor/fisiología , Adulto JovenRESUMEN
Exosomes are membrane-enclosed phospholipid extracellular vesicles, which can act as mediators of intercellular communication. Although the original features endow tumor-derived exosomes great potential as biomarkers, efficient isolation and detection methods remain challenging. Here, we presented a two-stage microfluidic platform (ExoPCD-chip), which integrates on-chip isolation and in situ electrochemical analysis of exosomes from serum. To promote exosomes capture efficiency, an improved staggered Y-shaped micropillars mixing pattern was designed to create anisotropic flow without any surface modification. By combining magnetic enrichment based on specific phosphatidylserine-Tim4 protein recognition with a new signal transduction strategy in a chip for the first time, the proposed platform enables highly sensitive detection for CD63 positive exosomes as low as 4.39 × 103 particles/mL with a linear range spanning 5 orders of magnitude, which is substantially better than the existing methods. The reduced volume of sample (30 µL) and simple affinity method also make it ideal for rapid downstream analysis of complex biofluids within 3.5 h. As a proof-of-concept, we performed exosomes analysis in human serum and liver cancer patients can be well discriminated from the healthy controls by the ExoPCD-chip. These results demonstrate that this proposed ExoPCD-chip may serve as a comprehensive exosome analysis tool and potential noninvasive diagnostic platform.
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Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Exosomas/metabolismo , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodos , Aptámeros de Nucleótidos/química , Carcinoma/diagnóstico , ADN Catalítico/química , Técnicas Electroquímicas/instrumentación , Diseño de Equipo , Hemina/química , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Fenómenos Magnéticos , Técnicas Analíticas Microfluídicas/instrumentación , Tetraspanina 30/químicaRESUMEN
Nitric oxide (NO) is a transcellular messenger involved in many physiological and pathological processes, but the real-time detection of NO in biological systems is still challenging due to its rapid diffusion, low concentration, and short half-life. A novel electrochemical sensing platform based on iron phthalocyanine (FePc) functionalized nitrogen-doped graphene (N-G) nanocomposites was constructed to achieve in situ monitoring of NO released from living cells on the sensing layer. By taking advantage of the synergetic effect of N-G and FePc nanocomposites, the N-G/FePc sensor displays excellent electrocatalytic activity toward NO with a high sensitivity of 0.21 µA µM-1 cm-2 and a low detection limit of 180 nmol L-1. The following layer-by-layer assembly of poly-l-lysine (PLL) and Nafion further improved the capacity of resisting disturbance as well as the biocompatibility of the sensing interface. The flexible design of the ITO substrate based electrode provides a more controlled cellular biosensing system which could capture molecular signals immediately after NO released from human umbilical vein endothelial cells (HUVECs). The exhibited additional features of high sensitivity, rapid response, and ease of operation implies that the proposed N-G/FePc/Nafion/PLL ITO biosensor is a promising powerful platform in various complex biological systems.
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Técnicas Biosensibles/métodos , Compuestos Ferrosos/química , Grafito/química , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Indoles/química , Óxido Nítrico/análisis , Nitrógeno/química , Supervivencia Celular , Células Cultivadas , Técnicas Electroquímicas , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Nanocompuestos/química , Óxido Nítrico/metabolismo , Factores de TiempoRESUMEN
The citrus red mite, Panonychus citri (McGregor), a major citrus pest distributed worldwide, has been found to be resistant to various insecticides and acaricides used in China. However, the molecular mechanisms associated with the abamectin resistance in this species have not yet been reported. In this study, results showed over-expression of a novel glutathione S-transferases (GSTs) gene (PcGSTm5) in abamectin-resistant P. citri. Quantitative real-time PCR analysis showed that the transcripts of PcGSTm5 were also significantly up-regulated after exposure to abamectin and the maximum mRNA expression level at nymphal stage. The recombinant protein of PcGSTm5-pET-28a produced by Escherichia coli showed a pronounced activity toward the conjugates of 1-chloro-2,4 dinitrobenzene (CDNB) and glutathione (GSH). The kinetics of CDNB and GSH and its optimal pH and thermal stability were also determined. Reverse genetic study through a new method of leaf-mediated dsRNA feeding further support a link between the expression of PcGSTm5 and abamectin resistance. However, no direct evidence was found in metabolism or inhibition assays to confirm the hypothesis that PcGSTm5 can metabolize abamectin. Finally, it is here speculated that PcGSTm5 may play a role in abamectin detoxification through other pathway such as the antioxidant protection.
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Acaricidas , Glutatión Transferasa/genética , Ivermectina/análogos & derivados , Tetranychidae/genética , Animales , Bioensayo , Resistencia a Medicamentos , Femenino , Genes/genética , Glutatión Transferasa/metabolismo , Tetranychidae/efectos de los fármacos , Tetranychidae/enzimologíaRESUMEN
The citrus red mite, Panonychus citri (McGregor), is a major citrus pest with a worldwide distribution and an extensive record of pesticide resistance. However, the underlying molecular mechanism associated with fenpropathrin resistance in this species have not yet been reported. In this study, synergist triphenyl phosphate (TPP) dramatically increased the toxicity of fenpropathrin, suggesting involvement of carboxylesterases (CarEs) in the metabolic detoxification of this insecticide. The subsequent spatiotemporal expression pattern analysis of PcE1, PcE7 and PcE9 showed that three CarEs genes were all over-expressed after insecticide exposure and higher transcripts levels were observed in different field resistant strains of P. citri. Heterologous expression combined with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) cytotoxicity assay in Spodoptera frugiperda (Sf9) cells revealed that PcE1-, PcE7- or PcE9-expressing cells showed significantly higher cytoprotective capability than parental Sf9 cells against fenpropathrin, demonstrating that PcEs probably detoxify fenpropathrin. Moreover, gene silencing through the method of leaf-mediated dsRNA feeding followed by insecticide bioassay increased the mortalities of fenpropathrin-treated mites by 31% (PcE1), 27% (PcE7) and 22% (PcE9), respectively, after individual PcE gene dsRNA treatment. In conclusion, this study provides evidence that PcE1, PcE7 and PcE9 are functional genes mediated in fenpropathrin resistance in P. citri and enrich molecular understanding of CarEs during the resistance development of the mite.
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Esterasas/genética , Ácaros/enzimología , Piretrinas/farmacología , Animales , Hidrolasas de Éster Carboxílico/genética , Resistencia a Medicamentos/genética , Esterasas/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Insecticidas/farmacología , Ácaros/efectos de los fármacos , SpodopteraRESUMEN
Chitinases are hydrolytic enzymes that are required for chitin degradation and reconstruction in arthropods. In this study, we report a cDNA sequence encoding a putative chitinase (PcCht1) from the citrus red mite, Panonychus citri. The PcCht1 (564 aa) possessed a signal peptide, a conserver domain, and a chitin-binding domain. Structural and phylogenetic analyses found that PcCht1 had high sequence similarity to chitinases in Tetranychus urticae. Real-time quantitative PCR analyses showed that the transcript levels of PcCht1 peaked periodically in larval and nymph stages. Moreover, significant increase of PcCht1 transcript level in the larvae was observed upon the exposure of diflubenzuron. In contrast, exposures of the larvae to diflubenzuron resulted in the decreased chitin content. Furthermore, through a feeding-based RNA interference approach, we were able to reduce the PcCht1 transcript level by 59.7 % in the larvae, and consequently the treated larvae showed a very low molting rate compared with the control. Our results expanded the understanding of the important role of PcCht1 in the growth and development of P. citri.
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Proteínas de Artrópodos/genética , Quitinasas/genética , Metamorfosis Biológica , Interferencia de ARN , Tetranychidae/crecimiento & desarrollo , Tetranychidae/genética , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/metabolismo , Secuencia de Bases , Quitinasas/metabolismo , Clonación Molecular , ADN Complementario/genética , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Ninfa/genética , Ninfa/crecimiento & desarrollo , Ninfa/metabolismo , Filogenia , ARN Mensajero/genética , Tetranychidae/enzimologíaRESUMEN
The production and uptake of yolk protein play an important role in the reproduction of all oviparous organisms. Vitellogenin (Vg) is the precursor of vitellin (Vn), which is the major egg storage protein, and vitellogenin receptor (VgR) is a necessary protein for the uptake of Vg into developing oocytes. In this paper, we characterize the full-length Vg and VgR, PcVg1 and PcVgR, respectively, of the citrus red mite Panonychus citri (McGregor). The PcVg1 cDNA is 5748 nucleotides (nt) with a 5553-nt open reading frame (ORF) coding for 1851 amino acids (aa), and the PcVgR is 6090 nt, containing an intact ORF of 5673 nt coding an expected protein of 1891 aa. The PcVg1 aa sequence shows a typical GLCG domain and several K/RXXR cleavage sites, and PcVgR comprises two ligand-binding domains, two epidermal growth factor (EGF)-like regions containing YWTD motifs, a transmembrane domain, and a cytoplasmic domain. An analysis of the aa sequences and phylogenetics implied that both genes were genetically distinct from those of ticks and insects. The transcriptional profiles determined by real-time quantitative PCR in different developmental stages showed that both genes present the same expressional tendencies in eggs, larvae, nymphs, and adults. This suggested that the biosynthesis and uptake of PcVg occurs coordinately. The strong reproductive capacity of P. citri has been hypothesized as an important factor in its resistance; consequently, understanding the molecular mechanisms regulating Vg and VgR are fundamental for mite control.
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Proteínas del Huevo , Receptores de Superficie Celular , Tetranychidae/genética , Tetranychidae/metabolismo , Vitelogeninas , Secuencias de Aminoácidos , Animales , Clonación Molecular , ADN Complementario/química , ADN Complementario/metabolismo , Proteínas del Huevo/genética , Proteínas del Huevo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Larva/genética , Filogenia , Estructura Terciaria de Proteína , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Tetranychidae/clasificación , Tetranychidae/crecimiento & desarrollo , Vitelogeninas/genética , Vitelogeninas/metabolismoRESUMEN
Superoxide dismutase (SOD) is a family of enzymes with multiple isoforms that possess antioxidative abilities in response to environmental stresses. Panonychus citri is one of the most important pest mites and has a global distribution. In this study, three distinct isoforms of SOD were cloned from P. citri and identified as cytoplasmic Cu-ZnSOD (PcSOD1), extracellular Cu-ZnSOD (PcSOD2), and mitochondrial MnSOD (PcSOD3). mRNA expression level analysis showed that all three isoforms were up-regulated significantly after exposure to the acaricide abamectin and to UV-B ultraviolet irradiation. In particular, PcSOD3 was up-regulated under almost all environmental stresses tested. The fold change of PcSOD3 expression was significantly higher than those of the two Cu-ZnSOD isoforms. Taken together, the results indicate that abamectin and UV-B can induce transcripts of all three SOD isoforms in P. citri. Furthermore, PcSOD3 seems to play a more important role in P. citri tolerance to oxidative stress.
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Proteínas de Artrópodos/genética , Superóxido Dismutasa/genética , Tetranychidae/genética , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/metabolismo , Clonación Molecular , ADN Complementario/genética , ADN Complementario/metabolismo , Datos de Secuencia Molecular , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Estrés Fisiológico , Superóxido Dismutasa/metabolismo , Tetranychidae/metabolismoRESUMEN
Chitin synthase synthesizes chitin, which is critical for the arthropod exoskeleton. In this study, we cloned the cDNA sequences of a chitin synthase 1 gene, PcCHS1, in the citrus red mite, Panonychus citri (McGregor), which is one of the most economically important pests of citrus worldwide. The full-length cDNA of PcCHS1 contains an open reading frame of 4605 bp of nucleotides, which encodes a protein of 1535 amino acid residues with a predicted molecular mass of 175.0 kDa. A phylogenetic analysis showed that PcCHS1 was most closely related to CHS1 from Tetranychus urticae. During P. citri development, PcCHS1 was constantly expressed in all stages but highly expressed in the egg stage (114.8-fold higher than in the adult). When larvae were exposed to diflubenzuron (DFB) for 6 h, the mite had a significantly high mortality rate, and the mRNA expression levels of PcCHS1 were significantly enhanced. These results indicate a promising use of DFB to control P. citri, by possibly acting as an inhibitor in chitin synthesis as indicated by the up-regulation of PcCHS1 after exposure to DFB.
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Proteínas de Artrópodos/genética , Quitina Sintasa/genética , Diflubenzurón/farmacología , Ácaros/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/clasificación , Secuencia de Bases , Quitina Sintasa/clasificación , Citrus/parasitología , Clonación Molecular , ADN Complementario/química , ADN Complementario/genética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Larva/efectos de los fármacos , Larva/genética , Larva/fisiología , Ácaros/genética , Ácaros/fisiología , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
The citrus red mite, Panonychus citri (McGregor), is a global citrus pest, and has developed severe resistance to several types of acaricides. However, the molecular mechanisms of resistance in this mite remain unknown. In this study, seven full-length cDNAs encoding glutathione S-transferases (GSTs) genes were identified and characterized in P. citri. The effects of pyridaben and fenpropathrin exposure on the expression of these genes were also investigated. Phylogenetic analysis revealed that the seven GSTs genes in P. citri cloned in this study belong to three different cytosolic classes, including four in mu, two in delta and one in zeta. Among these seven GSTs genes, the relative expression level of PcGSTm1 was significantly higher in adult than in the other life stages (egg, larvae and nymph). Compared with the control, the mRNA levels of the seven GST genes did not change significantly following exposure to pyridaben at LC10. However, RT-qPCR results showed that, when exposed to LC10 of fenpropathrin, six GSTs gene (PcGSTm1, PcGSTm3, PcGSTm4, PcGSTd1, PcGSTd2 and PcGSTz1) transcripts increased in a time-dependent manner. This is the first insight into the molecular characteristics of GSTs gene cDNAs in P. citri. The elevated GSTs gene transcripts following exposure to fenpropathrin might be one of the mechanisms involved in detoxification of this acaricide.
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Glutatión Transferasa/genética , Ácaros/enzimología , Ácaros/genética , Acaricidas/metabolismo , Acaricidas/toxicidad , Animales , Secuencia de Bases , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Glutatión Transferasa/metabolismo , Ácaros/clasificación , Ácaros/crecimiento & desarrollo , Datos de Secuencia Molecular , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Piretrinas/metabolismo , Piretrinas/toxicidad , Piridazinas/metabolismo , Piridazinas/toxicidad , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: To evaluate the effect of pretreatment by inhaling specific phosphodiesterase inhibitor on lung injury induced by cardiopulmonary bypass (CPB). METHODS: From April 2010 to November 2010, 30 patients were divided randomly into two groups: control group (n = 15) and milrinone group (n = 15). In milrinone group, 5 mg milrinone diluted by 5ml normal saline was inhaled per 8 h two days pre-operation. In control group, only 10 ml normal saline was inhaled. Blood samples were drawn from ulnar vein and radial artery pre-operation (T(0)), 30 min post-aortic unclamping (T(1)), at the end of operation (T(2)), 24 h, 72 h and 7 d post-operation (T(3)-T(5)). The following parameters were determined: TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), HSCRP (high-sensitivity C-reactive protein), MDA (malondialdehyde), MPO (myeloperoxidase) level and leucocyte count ratio of venous and arterial blood. And the values of pulmonary vascular resistance (PVR) and oxygenation index (OI) were measured through a Swan-Ganz catheter at the first 5 time points. RESULTS: PVR rose while OI declined at post-operation. But the range of above-mentioned indices in milrinone group was significantly smaller than that in control group. And the indices recovered much earlier in milrinone group. The levels of TNF-α, IL-6, HSCRP, MDA, MPO and leucocyte count ratio were not significantly different at T(0) between two groups and increased significantly after CPB in both groups. But the level of TNF-α (ng/L) was significantly lower at T(2), T(4), T(5) in milrinone group than that in control group (60 ± 5 vs 79 ± 7, 29 ± 6 vs 40 ± 8, 18 ± 5 vs 28 ± 7, all P < 0.05). The levels of IL-6 and MDA were significantly lower at T(1)-T(4) in milrinone group. The level of HSCRP became elevated post-operatively in both groups and reached its peak at 24 h post-operation, especially in control group. The level of MPO (µg/L) was significantly lower at T(2), T(3) and T(5) (134 ± 20 vs 190 ± 23, 142 ± 28 vs 178 ± 20, 65 ± 9 vs 75 ± 11, all P < 0.05). And the V/A ratio was significantly lower at T(1)-T(3) in milrinone group than in control group (1.12 ± 0.11 vs 1.37 ± 0.09, 1.07 ± 0.07 vs 1.25 ± 0.07, both P < 0.01). CONCLUSION: Inhaled milrinone may protect the lungs from acute injury induced by CPB. Inhaling milrinone is safe and feasible for the prevention of acute CPB-induced injury.
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Puente Cardiopulmonar/efectos adversos , Lesión Pulmonar/prevención & control , Milrinona/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Síndrome de Dificultad Respiratoria/prevención & control , Adulto , Anciano , Femenino , Humanos , Lesión Pulmonar/etiología , Masculino , Inhaladores de Dosis Medida , Persona de Mediana Edad , Milrinona/administración & dosificación , Inhibidores de Fosfodiesterasa/administración & dosificación , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
Exosomes are natural delivery vehicles because of their original feature such as low immunogenicity, excellent biocompatibility, and migration capability. Engineering exosomes with appropriate ligands are effective approaches to improve the low cellular uptake efficiency of exosomes. However, current strategies face considerable challenges due to the tedious and labor-intensive operational process. Here, we designed a novel peptides-equipped exosomes platform which can be assembled under convenient and mild reaction condition. Cell-penetrating peptides (CPPs) was conjugated on HepG2 cells-derived exosomes surface which can not only enhance the penetrating capacity of exosomes but also assist exosomes in loading antisense oligonucleotides (ASOs). The cellular uptake mechanism was investigated and we compared the difference between natural exosomes and modified exosomes. The resulting nanosystem demonstrated a preferential tropism for cells that are parented to their source tumor cells and could remarkably increase the cellular delivery of G3139 with efficient downregulation of antiapoptotic Bcl-2. This work developed a rapid strategy for intracellular delivery of nucleic acids, thus providing more possibilities toward personalized cancer medicine.
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Péptidos de Penetración Celular/química , Portadores de Fármacos/química , Exosomas/química , Oligodesoxirribonucleótidos Antisentido/farmacología , Tionucleótidos/farmacología , Péptidos de Penetración Celular/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Portadores de Fármacos/metabolismo , Exosomas/metabolismo , Silenciador del Gen/efectos de los fármacos , Células Hep G2 , Humanos , Oligodesoxirribonucleótidos Antisentido/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tionucleótidos/genéticaRESUMEN
L-amino acid oxidase (ThLAAO) secreted by Trichoderma harzianum ETS323 is a ï¬avoenzyme with antimicrobial characteristics. In this study, we transformed the ThLAAO gene into tobacco to elucidate whether ThLAAO can activate defense mechanisms and confer resistance against phytopathogens. Transgenic tobacco overexpressing ThLAAO showed enhanced resistance against Sclerotinia sclerotiorum and Botrytis cinerea and activated the expression of defense-related genes and the genes involved in salicylic acid, jasmonic acid, and ethylene biosynthesis accompanied by substantial accumulation of H2O2 in chloroplasts, cytosol around chloroplasts, and cell membranes of transgenic tobacco. Scavenge of H2O2 with ascorbic acid abolished disease resistance against B. cinerea infection and decreased the expression of defense-related genes. ThLAAO-FITC application on tobacco protoplast or overexpression of ThLAAO-GFP in tobacco revealed the localization of ThLAAO in chloroplasts. Chlorophyll a/b binding protein (CAB) was isolated through ThLAAO-ConA affinity chromatography. The pull down assay results confirmed ThLAAO-CAB binding. Application of ThLAAO-Cy5.5 on cabbage roots promptly translocated to the leaves. Treatment of ThLAAO on cabbage roots induces systemic resistance against B. cinerea. Overall, these results demonstrate that ThLAAO may target chloroplast and activate defense mechanisms via H2O2 signaling to confer resistance against S. sclerotiorum and B. cinerea.
Asunto(s)
Ascomicetos , Botrytis , Resistencia a la Enfermedad/genética , Proteínas Fúngicas/genética , Hypocreales/genética , L-Aminoácido Oxidasa/genética , Nicotiana/inmunología , Enfermedades de las Plantas/inmunología , Proteínas Fúngicas/fisiología , Peróxido de Hidrógeno/metabolismo , Hypocreales/enzimología , L-Aminoácido Oxidasa/fisiología , Enfermedades de las Plantas/microbiología , Plantas Modificadas Genéticamente , Reacción en Cadena en Tiempo Real de la Polimerasa , Nicotiana/genética , Nicotiana/microbiologíaRESUMEN
The person-centered account of moral judgments is important since immoral behaviors are diagnostic of an individual's character. The present study explored how the professional stereotypes associated with the agents shaped the way people perceiving moral/immoral behaviors. The behavioral ratings and neural responses (i.e., P200, N2, LPC event-related potentials (ERPs)) to moral/immoral behaviors done by agents with respectable or ordinary professional roles were recorded and compared. Behaviorally, we found that participants rated the agent with a respectable professional role behaving immorally as more dislikable comparing to the agent with an ordinary professional role. For ERPs, we found that: 1) the agents with respectable professional roles elicited larger P200 than agents with ordinary professional roles did; 2) immoral behavior elicited larger LPC than moral behaviors did; 3) for agents with respectable professional roles, the immoral behaviors elicited significantly more positive N2 than the moral behaviors did whereas this difference was not significant for the agents with ordinary professional roles. The immoral behaviors done by agents with respectable professional roles elicited more positive N2 than the immoral behavior done by agents with ordinary professional roles. Moreover, this effect was correlated with the participants' subjective rating of the professional roles' respectable level. These results suggest that 1) the more the agents with respectable professional roles are respected, the more dislikable they became when behaving immorally; 2) the moral stereotype associated with professional roles can influence the early processing stage reflected in N2 but not the later evaluative process reflected in LPC.