RESUMEN
The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.
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Metagenoma , Microbiota , Ovinos/genética , Animales , Transcriptoma , Rumen , Rumiantes/genéticaRESUMEN
Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). Upon pathological stimulation, microglia are converted from a surveillant to an overactivated phenotype. However, the molecular characters of proliferating microglia and their contributions to the pathogenesis of neurodegeneration remain unclear. Here, we identify chondroitin sulfate proteoglycan 4 (Cspg4, also known as neural/glial antigen 2)-expressing microglia as a specific subset of microglia with proliferative capability during neurodegeneration. We found that the percentage of Cspg4+ microglia was increased in mouse models of PD. The transcriptomic analysis of Cspg4+ microglia revealed that the subcluster Cspg4high microglia displayed a unique transcriptomic signature, which was characterized by the enrichment of orthologous cell cycle genes and a lower expression of genes responsible for neuroinflammation and phagocytosis. Their gene signatures were also distinct from that of known disease-associated microglia. The proliferation of quiescent Cspg4high microglia was evoked by pathological α-synuclein. Following the transplantation in the adult brain with the depletion of endogenous microglia, Cspg4high microglia grafts showed higher survival rates than their Cspg4- counterparts. Consistently, Cspg4high microglia were detected in the brain of AD patients and displayed the expansion in animal models of AD. These findings suggest that Cspg4high microglia are one of the origins of microgliosis during neurodegeneration and may open up a avenue for the treatment of neurodegenerative diseases.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Ratones , Animales , Microglía/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedades Neurodegenerativas/metabolismo , FagocitosisRESUMEN
The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.
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Conexinas , Neuralgia , Especies Reactivas de Oxígeno , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Masculino , Especies Reactivas de Oxígeno/metabolismo , Neuralgia/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Ratones , Femenino , Conexinas/metabolismo , Conexinas/genética , Canales de Potasio de Rectificación Interna/metabolismo , Dolor Facial/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ganglio del Trigémino/metabolismo , Hiperalgesia/metabolismo , Ratones Endogámicos C57BL , Sistema de Señalización de MAP Quinasas/fisiologíaRESUMEN
Jasmonic acid (JA) and gibberellin (GA) coordinately regulate plant developmental programs and environmental cue responses. However, the fine regulatory network of the cross-interaction between JA and GA remains largely elusive. In this study, we demonstrate that MdNAC72 together with MdABI5 positively regulates anthocyanin biosynthesis through an exquisite MdNAC72-MdABI5-MdbHLH3 transcriptional cascade in apple. MdNAC72 interacts with MdABI5 to promote the transcriptional activation of MdABI5 on its target gene MdbHLH3 and directly activates the transcription of MdABI5. The MdNAC72-MdABI5 module regulates the integration of JA and GA signals in anthocyanin biosynthesis by combining with JA repressor MdJAZ2 and GA repressor MdRGL2a. MdJAZ2 disrupts the MdNAC72-MdABI5 interaction and attenuates the transcriptional activation of MdABI5 by MdNAC72. MdRGL2a sequesters MdJAZ2 from the MdJAZ2-MdNAC72 protein complex, leading to the release of MdNAC72. The E3 ubiquitin ligase MdSINA2 is responsive to JA and GA signals and promotes ubiquitination-dependent degradation of MdNAC72. The MdNAC72-MdABI5 interface fine-regulates the integration of JA and GA signals at the transcriptional and posttranslational levels by combining MdJAZ2, MdRGL2a, and MdSINA2. In summary, our findings elucidate the fine regulatory network connecting JA and GA signals with MdNAC72-MdABI5 as the core in apple.
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Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Giberelinas , Malus , Oxilipinas , Proteínas de Plantas , Transducción de Señal , Ubiquitinación , Oxilipinas/metabolismo , Malus/genética , Malus/metabolismo , Ciclopentanos/metabolismo , Ubiquitinación/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Giberelinas/metabolismo , Proteolisis/efectos de los fármacos , Antocianinas/metabolismo , Unión Proteica/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Modelos BiológicosRESUMEN
BACKGROUND: The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC). METHODS: A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM. RESULTS: The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338). CONCLUSIONS: Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.
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Adenocarcinoma Mucinoso , Axila , Neoplasias de la Mama , Ganglios Linfáticos , Metástasis Linfática , Humanos , Femenino , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Persona de Mediana Edad , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Adulto , Anciano , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundario , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ultrasonografía/métodos , Biomarcadores de Tumor/metabolismoRESUMEN
Inward-rectifying K+ channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K+ homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway.
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Hiperalgesia , Receptor del Glutamato Metabotropico 5 , Ratas , Ratones , Masculino , Animales , Hiperalgesia/etiología , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Nervio Mandibular/metabolismo , Nervio Mandibular/cirugíaRESUMEN
Abscisic acid (ABA) induces chlorophyll degradation and leaf senescence; however, the molecular mechanism remains poorly understood, especially in woody plants. In this study, we found that MdABI5 plays an essential role in the regulation of ABA-triggered leaf senescence in Malus domestica (apple). Through yeast screening, three transcription factors, MdBBX22, MdWRKY40 and MdbZIP44, were found to interact directly with MdABI5 in vitro and in vivo. Physiological and biochemical assays showed that MdBBX22 delayed leaf senescence in two pathways. First, MdBBX22 interacted with MdABI5 to inhibit the transcriptional activity of MdABI5 on the chlorophyll catabolic genes MdNYE1 and MdNYC1, thus negatively regulating chlorophyll degradation and leaf senescence. Second, MdBBX22 interacted with MdHY5 to interfere with the transcriptional activation of MdHY5 on MdABI5, thereby inhibiting the expression of MdABI5, which also contributed to the delay of leaf senescence. MdWRKY40 and MdbZIP44 were identified as positive regulators of leaf senescence. They accelerated MdABI5-promoted leaf senescence through the same regulatory pathways, i.e., interacting with MdABI5 to enhance the transcriptional activity of MdABI5 on MdNYE1 and MdNYC1. Taken together, our results suggest that MdABI5 works with its positive or negative interaction partners to regulate ABA-mediated leaf senescence in apple, in which it acts as a core regulator. The antagonistic regulation pathways ensure that plants respond to external stresses flexibly and efficiently. Our results provide a concept for further study on the regulation mechanisms of leaf senescence.
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Ácido Abscísico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Malus/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Envejecimiento/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/fisiología , Malus/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/fisiología , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/fisiología , Factores de Transcripción/metabolismo , Factores de Transcripción/fisiologíaRESUMEN
TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors play crucial roles in plant abiotic stresses. However, little is known about the role of TCP genes in the drought stress tolerance of apple. Here, we found that abscisic acid (ABA) and drought treatment reduced the expression of MdTCP46, and overexpression of MdTCP46 reduced ABA sensitivity and drought stress resistance. MdTCP46 was found to interact with MdABI5 both in vitro and in vivo, and this interaction was essential for drought resistance via the ABA-dependent pathway. Overexpression of MdABI5 enhanced ABA sensitivity and drought stress resistance by directly activating the expression of MdEM6 and MdRD29A. MdTCP46 significantly suppressed the transcriptional activity of MdABI5, thereby negatively regulating MdABI5-mediated ABA signalling and drought response. Overall, our results demonstrate that the MdTCP46-MdABI5-MdEM6/MdRD29A regulatory module plays a key role in the modulation of ABA signalling and the drought stress response. These findings provide new insight into the role of MdTCP46 in ABA signalling and abiotic stress responses.
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Arabidopsis , Malus , Ácido Abscísico/metabolismo , Arabidopsis/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
INTRODUCTION: The aim was to analyze the morphological changes of root apex in anterior teeth with periapical periodontitis. METHODS: 32 untreated anterior teeth with periapical periodontitis were enrolled, compared with the healthy contralateral teeth. Two-dimensional measurement of Cone-beam computed tomography was used to determine the location and measure diameter of the apical constriction according to Schell's methods. An open-source software (3D Slicer) was used to reconstruct the teeth. The apical constriction form was analysis according to Schell's topography. The distances of apical constriction to apical foramen and anatomical apex were measured respectively. RESULTS: The difference value between buccolingual and mesiodistal diameter was (0.06 ± 0.09) mm and (0.04 ± 0.04) mm in periapical periodontitis and controls (p < 0.05). The mean distance between apical constriction and anatomical apex was significantly shorter in periapical periodontitis than controls, so was the mean distance of apical constriction to apical foramen. The most common form of apical constriction was flaring (65.6%) in periapical periodontitis. CONCLUSIONS: The anterior teeth with periapical periodontitis had shorter distances of apical constriction to anatomical apex and apical foramen, bigger disparities between the diameters of buccolingual and mesiodistal, and higher proportion of flaring apical constriction.
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Periodontitis Periapical , Tomografía Computarizada de Haz Cónico , Humanos , Periodontitis Periapical/complicaciones , Periodontitis Periapical/diagnóstico por imagen , Tratamiento del Conducto Radicular/métodos , Ápice del Diente/diagnóstico por imagenRESUMEN
Abscisic acid (ABA) induces anthocyanin biosynthesis in many plant species. However, the molecular mechanism of ABA-regulated anthocyanin biosynthesis remains unclear. As a crucial regulator of ABA signaling, ABSCISIC ACID-INSENSITIVE5 (ABI5) is involved in many aspects of plant growth and development, yet its regulation of anthocyanin biosynthesis has not been elucidated. In this study, we found that MdABI5, the apple homolog of Arabidopsis ABI5, positively regulated ABA-induced anthocyanin biosynthesis. A series of biochemical tests showed that MdABI5 specifically interacts with basic helix-loop-helix 3 (MdbHLH3), a positive regulator of anthocyanin biosynthesis. MdABI5 enhanced the binding of MdbHLH3 to its target genes dihydroflavonol 4-reductase (MdDFR) and UDP flavonoid glucosyl transferase (MdUF3GT). In addition, MdABI5 directly bound to the promoter of MdbHLH3 to activate its expression. Moreover, MdABI5 enhanced ABA-promoted interaction between MdMYB1 and MdbHLH3. Finally, antisense suppression of MdbHLH3 significantly reduced anthocyanin biosynthesis promoted by MdABI5, indicating that MdABI5-promoted anthocyanin biosynthesis was dependent on MdbHLH3. Taken together, our data suggest that MdABI5 plays a positive role in ABA-induced anthocyanin biosynthesis by modulating the MdbHLH3-MdMYB1 complex. Our work broadens the regulatory network of ABA-mediated anthocyanin biosynthesis, providing new insights to further study the transcriptional regulatory mechanisms behind this process.
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Antocianinas/biosíntesis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Malus , Proteínas de Plantas/metabolismo , Ácido Abscísico , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación de la Expresión Génica de las Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Regiones Promotoras GenéticasRESUMEN
KEY MESSAGE: MdBZR1 directly binds to the promoter of MdABI5 and suppresses its expression to mediate ABA response. The plant hormones brassinosteroids (BRs) and abscisic acid (ABA) antagonistically regulate various aspects of plant growth and development. However, the association between BR and ABA signaling is less clear. Here, we identified MdBZR1 in apple (Malus domestica) and demonstrated that it was activated by BRs and could respond to ABA treatment. Overexpression of MdBZR1 in apple calli and Arabidopsis reduced ABA-hypersensitive phenotypes, suggesting that MdBZR1 negatively regulates ABA signaling. Subsequently, we found that MdBZR1 directly bound to the promoter region of MdABI5 and suppressed its expression. MdABI5 was significantly induced by ABA treatment. And overexpression of MdABI5 in apple calli increased sensitivity to ABA. Ectopic expression of MdABI5 in Arabidopsis inhibited seed germination and seedling growth. In addition, overexpression of MdBZR1 partially attenuated MdABI5-mediated ABA sensitivity. Taken together, our data indicate that MdBZR1 directly binds to the promoter of MdABI5 and suppresses its expression to antagonistically mediate ABA response. Our work contributes to the functional studies of BZR1 and further broadens the insight into the between BR and ABA signaling.
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Ácido Abscísico/metabolismo , Malus/genética , Proteínas de Plantas/genética , Ácido Abscísico/farmacología , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Malus/efectos de los fármacos , Malus/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Estrés Salino/genéticaRESUMEN
Teosinte branched1/cycloidea/proliferating (TCP) transcription factors play a broad role in plant growth and development, but their involvement in the regulation of anthocyanin biosynthesis is currently unclear. In this study, anthocyanin biosynthesis induced by different light intensities in apple (Malus domestica) was found to be largely dependent on the functions of the MdMYB1 and MdTCP46 transcription factors. The expression of MdTCP46 was responsive to high light intensity, and under these conditions it promoted anthocyanin biosynthesis by direct interactions with MdMYB1 that enhanced the binding of the latter to its target genes. MdTCP46 also interacted with a bric-a-brac/tramtrack/broad (BTB) protein, MdBT2, that is responsive to high light intensity, which ubiquitinated MdTCP46 and mediated its degradation via the 26S proteasome pathway. Our results demonstrate that the dynamic regulatory module MdBT2-MdTCP46-MdMYB1 plays a key role in modulating anthocyanin biosynthesis at different light intensities in apple, and provides new insights into the post-transcriptional regulation of TCP proteins.
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Malus , Antocianinas , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Sugars play important roles in plant growth and development, crop yield and quality, as well as responses to abiotic stresses. Abscisic acid (ABA) is a multifunctional hormone. However, the exact mechanism by which ABA regulates sugar accumulation is largely unknown in plants. Here, we tested the expression profile of several sugar transporter and amylase genes in response to ABA treatment. MdSUT2 and MdAREB2 were isolated and genetically transformed into apple (Malus domestica) to investigate their roles in ABA-induced sugar accumulation. The MdAREB2 transcription factor was found to bind to the promoters of the sugar transporter and amylase genes and activate their expression. Both MdAREB2 and MdSUT2 transgenic plants produced more soluble sugars than controls. Furthermore, MdAREB2 promoted the accumulation of sucrose and soluble sugars in an MdSUT2-dependent manner. Our results demonstrate that the ABA-responsive transcription factor MdAREB2 directly activates the expression of amylase and sugar transporter genes to promote soluble sugar accumulation, suggesting a mechanism by which ABA regulates sugar accumulation in plants.
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Amilasas/genética , Regulación de la Expresión Génica de las Plantas , Malus/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Plantas/genética , Azúcares/metabolismo , Factores de Transcripción/metabolismo , Ácido Abscísico/farmacología , Amilasas/metabolismo , Frutas/efectos de los fármacos , Frutas/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Malus/efectos de los fármacos , Malus/enzimología , Proteínas de Transporte de Membrana/metabolismo , Modelos Biológicos , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Solubilidad , Sacarosa/metabolismo , Factores de Transcripción/genéticaRESUMEN
Phytohormone abscisic acid (ABA) regulates many important processes in plants. It is a major molecule facilitating signal transduction during the abiotic stress response. In this study, an ABA-inducible transcription factor gene, MdAREB2, was identified in apple. Transgenic analysis was performed to characterize its function in ABA sensitivity. Overexpression of the MdAREB2 gene increased ABA sensitivity in the transgenic apple compared with the wild-type (WT) control. In addition, it was found that the protein MdAREB2 was phosphorylated at a novel site Thr411 in response to ABA. A yeast two-hybridization screen of an apple cDNA library demonstrated that a protein kinase, MdCIPK22, interacted with MdAREB2. Their interaction was further verified with Pull Down and Co-IP assays. A series of transgenic analyses in apple calli and plantlets showed that MdCIPK22 was required for ABA-induced phosphorylation at Thr411 of the MdAREB2 protein and enhanced its stability and transcriptional activity. Finally, it was found that MdCIPK22 increased ABA sensitivity in an MdAREB2-dependent manner. Our findings indicate a novel phosphorylation site in CIPK-AREB regulatory module for the ABA signalling pathway, which would be helpful for researchers to identify the functions of uncharacterized homologs in the future.
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Ácido Abscísico/metabolismo , Malus/enzimología , Proteínas de Plantas/metabolismo , Proteínas Quinasas/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Malus/genética , Fosforilación , Plantas Modificadas Genéticamente , Unión Proteica , Treonina/metabolismo , Transcripción GenéticaRESUMEN
Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.
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Enfermedad de Alzheimer/psicología , Apolipoproteína E4/metabolismo , Receptores de Mineralocorticoides/genética , Enfermedad de Alzheimer/metabolismo , Animales , Ansiedad/metabolismo , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/metabolismo , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/fisiología , Apolipoproteínas E/genética , Encéfalo/metabolismo , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario , Hipotálamo , Masculino , Ratones , Ratones Transgénicos , Sistema Hipófiso-Suprarrenal , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Regulación hacia ArribaRESUMEN
Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA-challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of allergic airway inflammation in OVA-challenged WT mice, but not further ameliorated allergic airway inflammation in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis.
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Asma/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Melatonina/biosíntesis , Neumonía/metabolismo , Receptor Toll-Like 9/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Hipersensibilidad/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
The apolipoprotein E (ApoE) É4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE É3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.
Asunto(s)
Ansiedad/genética , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Conducta Animal , Estrés Psicológico/genética , Enfermedad de Alzheimer , Animales , Ansiedad/psicología , Enfermedad Crónica , Cognición , Proteína Ácida Fibrilar de la Glía/genética , Humanos , Masculino , Memoria a Largo Plazo , Ratones , Ratones Transgénicos , Restricción Física , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND/AIMS: Postpartum hemorrhage (PPH) is a life-threatening condition with a worldwide occurrence. The purpose of this study is to evaluate the efficacy and safety of a reflexed compression suture in controlling severe atonic PPH with placenta accreta. METHODS: Eleven women with severe PPH due to uterine inertia or placenta accreta were administered the reflexed compression suture. The procedure was to reflex the fundus onto the anterior wall of the uterus for compressing hemostasis and to form a 'belt-like' binding suture to reinforce the effectiveness of pressing the myometrium. RESULTS: Ten of the 11 women (90.9%) were successfully treated with the suture, and the uterus was preserved. None of these patients developed complications related to this method. Only in 1 patient with placenta increta could the bleeding not be stanched, and a peripartum hysterectomy was performed. Two women had pregnancies after the suture. CONCLUSION: The reflexed compression suture is a simple, swift, safe and effective technique of controlling uterine atonic bleeding, particularly in patients with an abnormally adherent placenta. The advantage of not having to conduct a hysterotomy also lies in reducing the duration of anesthesia and blood loss.
Asunto(s)
Procedimientos Quirúrgicos Obstétricos/métodos , Hemorragia Posparto/cirugía , Adulto , Femenino , Humanos , Placenta Accreta , Hemorragia Posparto/etiología , Embarazo , Técnicas de Sutura , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of a symbol "&" compression suture technique in controlling severe atonic postpartum hemorrhage with placenta previa accreta during cesarean delivery. METHODS: Nine women with heavy postpartum bleeding from uterine inertia and placenta previa percret, which did not react to conventional initial management protocols, were underwent the suture in the shape of symbol "&" in China Meitan General Hospital. The suture procedure was to staple the anterior and posterior walls (of the lower uterine segment as well as corpus uterus) together using number 1 chromic catgut, with a cross at about 2 cm above the upper boundary of lower uterine segment. RESULTS: Symbol "&" compression suture was capable of stanching the postpartum hemorrhage immediately in all nine women. None of these patients developed complications related to this method. Subsequent pregnancies after the suture were occurred in two women and delivered with repeat cesarean section. CONCLUSION: Symbol "&" compression suture is a simple, safe and highly effective technique to control the treatment-resistant uterine atonic bleeding, particularly in previous cesarean scar at lower segment and placenta previa accreta.
Asunto(s)
Placenta Accreta/cirugía , Placenta Previa/cirugía , Hemorragia Posparto/cirugía , Inercia Uterina/cirugía , Adulto , Cesárea , Cesárea Repetida , China , Cicatriz/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Hemorragia Posparto/etiología , Embarazo , Presión , Grapado Quirúrgico , Técnicas de Sutura , Suturas , Útero/cirugía , Adulto JovenRESUMEN
OBJECTIVE: Previous studies reported that environmental enrichment might induce various beneficial effects in the central nervous system. However, the effect of environmental factors on endogenous estrogen level was not investigated. The present study was designed to examine the effect of enriched environment on endogenous estrogen in hippocampus and behavioral outcomes. METHODS: Behavioural measurements, including open field, elevated plus maze and Morris water maze, were used to evaluate anxiety and learning and memory of the male C57BL/6J mice that were housed in enriched environment for five months. In addition, the estrogen and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were measured. RESULTS: We found that environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. In addition, the mice raised in enriched environment showed decreased endogenous estrogen levels both in the hippocampus and plasma compared to controls. Furthermore, our results indicated that environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus. CONCLUSION: In conclusion, environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. Lastly, environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus and decreased plasma estrogen level. The possible mechanism remained to be determined.