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The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses.
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BACKGROUND: To determine whether a dual-isocenter volumetrically modulated arc therapy (VMAT) technique results in lower normal pulmonary dosage compared to a traditional single isocenter technique for boot-shaped lung cancer. METHODS: A cohort of 15 patients with advanced peripheral or central lung cancer who had metastases in the mediastinum and supraclavicular lymph nodes was randomly selected for this retrospective study. VMAT plans were generated for each patient using two different beam alignment techniques with the 6-MV flattening filter-free (FFF) photon beam: single-isocenter jaw-tracking VMAT based on the Varian TrueBeam linear accelerator (S-TV), and dual-isocenter VMAT based on both TrueBeam (D-TV) and Halcyon linear accelerator (D-HV). For all 45 treatment plans, planning target volume (PTV) dose coverage, conformity/homogeneity index (CI/HI), mean heart dose (MHD), mean lung dose (MLD) and the total lung tissue receiving 5, 20, 30 Gy (V5, V20, V30) were evaluated. The monitor units (MUs), delivery time, and plan quality assurance (QA) results were recorded. RESULTS: The quality of the objectives of the three plans was comparable to each other. In comparison with S-TV, D-TV and D-HV improved the CI and HI of the PTV (p < 0.05). The MLD was 13.84 ± 1.44 Gy (mean ± SD) for D-TV, 14.22 ± 1.30 Gy and 14.16 ± 1.42 Gy for S-TV and D-HV, respectively. Lungs-V5Gy was 50.78 ± 6.24%, 52.00 ± 7.32% and 53.36 ± 8.48%, Lungs-V20Gy was 23.72 ± 2.27%, 26.18 ± 2.86% and 24.96 ± 3.09%, Lungs-V30Gy was 15.69 ± 1.76%, 17.20 ± 1.72% and 16.52 ± 2.07%. Compared to S-TV, D-TV provided statistically significant better protection for the total lung, with the exception of the lungs-V5. All plans passed QA according the gamma criteria of 3%/3 mm. CONCLUSIONS: Taking into account the dosimetric results and published clinical data on radiation-induced pulmonary injury, dual-isocenter jaw-tracking VMAT may be the optimal choice for treating boot-shaped lung cancer.
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Estudios de Factibilidad , Neoplasias Pulmonares , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Pulmonares/radioterapia , Órganos en Riesgo/efectos de la radiación , Estudios Retrospectivos , Aceleradores de Partículas/instrumentaciónRESUMEN
Background: Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). However, it can cause implicit RT-induced injury by irradiating normal brain tissue. To date, there have been no detailed reports on the radiated exact location in the brain, the corresponding radiation dose, and their relationship. Methods: We analyzed 803 Chinese NPC patients treated with RT and used a CT brain template in a Montreal Neurological Institute (MNI) space to compare the group differences in RT dose distribution for different RT technologies (IMRT or VMAT). Results: Brain regions that received high doses (>50â Gy) of radiation were mainly located in parts of the temporal and limbic lobes, where radioactive damage often occurs. Brain regions that accepted higher doses with IMRT were mainly located near the anterior region of the nasopharyngeal tumor, while brain regions that accepted higher doses with VMAT were mainly located near the posterior region of the tumor. No significant difference was detected between IMRT and VMAT for T1 stage patients. For T2 stage patients, differences were widely distributed, with VMAT showing a significant dose advantage in protecting the normal brain tissue. For T3 stage patients, VMAT showed an advantage in the superior temporal gyrus and limbic lobe, while IMRT showed an advantage in the posterior cerebellum. For T4 stage patients, VMAT showed a disadvantage in protecting the normal brain tissue. These results indicate that IMRT and VMAT have their own advantages in sparing different organs at risk (OARs) in the brain for different T stages of NPC patients treated with RT. Conclusion: Our approach for analyzing dosimetric characteristics in a standard MNI space for Chinese NPC patients provides greater convenience in toxicity and dosimetry analysis with superior localization accuracy. Using this method, we found interesting differences from previous reports: VMAT showed a disadvantage in protecting the normal brain tissue for T4 stage NPC patients.
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Abacus-based mental calculation (AMC) has been shown to be effective in promoting math ability in children. Given that AMC relies on a visuospatial strategy to perform rapid and precise arithmetic, previous studies mostly focused on the promotion of AMC training on arithmetic ability and mathematical visual-spatial ability, as well as its transfer of advanced cognitive ability. However, little attention has been given to its impact on basic numerical comparison ability. Here, we aim to examine whether and how long-term AMC training impacts symbolic and non-symbolic numerical comparisons. The distance effect (DE) was utilized as a marker, indicating that the comparison between two numbers becomes faster as their numerical distance enlarges. In the current study, forty-one children matched for age and sex were recruited at primary school entry and randomly assigned to the AMC group and the control group. After three years of training, the event-related potential (ERP) recording technique was used to explore the temporal dynamics of number comparison, of which tasks were given in symbolic (Arabic number) or non-symbolic (dot array) format. In the symbolic task, the children in the AMC group showed a smaller DE than those in the control group. Two ERP components, N1 and P2p, located in parietal areas (PO7, PO8) were selected as neural markers of numerical processing. Both groups showed DE in the P2p component in both tasks, but only the children in the AMC group showed DE in the N1 component in the non-symbolic task. In addition, the DE size calculated from reaction times and ERP amplitudes was correlated with higher cognitive capacities, such as coding ability. Taken together, the present results provide evidence that long-term AMC training may be beneficial for numerical processing in children, which may be associated with neurocognitive indices of parietal brain regions.
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Mapeo Encefálico , Encéfalo , Niño , Humanos , Mapeo Encefálico/métodos , Potenciales Evocados , Matemática , Tiempo de ReacciónRESUMEN
Objective: To study the feasibility of intensity modulated radiation therapy (IMRT) for stage N0 nasopharyngeal carcinoma (NPC) and its parotid gland (PG) function preservation from physical and dosimetric aspects. Methods: All the clinical data of 77 patients with pathologically confirmed T1-4N0M0 NPC who received radiotherapy between July 2017 and October 2019 in the Radiotherapy Center of Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University were analyzed retrospectively. Three-dimensional conformal radiotherapy (3D-CRT) and IMRT were used in 35 and 42 cases, respectively. The treatment efficiency and the dosimetry differences of the PG in the intensity modulation plan were compared between groups. Quantitative monitoring of 99mTc radionuclide imaging of PG was performed before, at the end of, and 3, 6, and 12 months after radiotherapy. The degree of PG function injury and xerostomia was compared between groups at the end of radiotherapy and 12 months later. Results: Higher minimal, maximal, and average irradiation doses of PG were determined in 3D-CRT-treated patients compared with IMRT-treated cases (P < 0.05). Compared with before radiotherapy, the PG uptake index (UI) and excretion index (EI) of both cohorts of patients decreased to varying degrees at the end of radiotherapy, with PG function injury and xerostomia symptoms observed in all cases but with no obvious difference between groups (P > 0.05). To a certain extent, the PG function recovered and the xerostomia symptoms relieved in both groups 12 months after radiotherapy, with better improvements in IMRT group versus 3D-CRT group. Conclusion: IMRT has similar short-term efficacy to 3D-CRT in treating patients with stage N0 NPC, but it can effectively reduce the dose of PG radiotherapy and protect the PG function on the premise of ensuring sufficient tumor coverage and dose, showing certain dosimetry advantages.
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Neoplasias Nasofaríngeas , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Xerostomía , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapia , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/patología , Glándula Parótida/efectos de la radiación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Xerostomía/etiologíaRESUMEN
Objective: Parotid gland (PG) is a radiosensitive organ, and xerostomia (XS) is a key factor affecting patients' life quality after conventional radiotherapy for head and neck tumors. In this study, dosimetry analysis was performed on PG stem cell preservation in intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods: All clinical data of 80 NPC patients diagnosed pathologically in the Radiotherapy Department of Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University from August 2017 to September 2019 were retrospectively analyzed. Patients were assigned to a regular group and a restricted group according to different IMRT plans, in which a dose limitation for the parotid duct was added in the restricted group in addition to the conventional plan used in the regular group to minimize the parotid duct radiation dose. The differences in planning target volume (PTV) dose distribution, organ at risk (OAR) dose, and dose to the PG and its ducts were compared between the two groups. Results: Significantly higher mean irradiation doses of the brainstem, mandible, and oral cavity were determined in the restricted group compared with the regular group (P > 0.05), but there was no significant difference in the mean dose of other OARs irradiated (P > 0.05). As compared to the irradiation of bilateral PGs, no statistical differences were found in the mean irradiation dose and V30 between regular and restricted groups (P > 0.05), but lower V20 and higher V45 were determined in the restricted group (P < 0.05). The mean irradiation dose, V15, V20, and V26 of bilateral parotid ducts were lower in the restricted group as compared to the regular group (P < 0.05). Conclusion: IMRT for NPC can effectively reduce the mean irradiation dose and play a PG stem cell preservation role by giving specific dose limitation conditions to the parotid duct area without affecting PTV dose distribution and OAR irradiation dose, which has certain feasibility.
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OBJECTIVE: To investigate the effects of three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) on parotid gland function and quality of life in patients with nasopharyngeal carcinoma (NPC). METHODS: Ninety-six patients with NPC diagnosed and treated in our hospital were divided into two groups using a random number table. The control group was treated with three-dimensional conformal radiotherapy and the research group was treated with intensity-modulated radiotherapy. Observation and comparison were conducted for differences of baseline indicators between the two groups including; short-term response rate, relevant indicators regarding parotid gland function before and after treatment, uptake index (UI) and excretion index (EI), dry mouth (xerostomia) grading and quality of life indicators after treatment, and the prognosis of patients. RESULTS: There was no significant difference in baseline data between the two groups (all P>0.05). The short-term response rate in the research group was significantly higher than that in the control group (P<0.05). After treatment, UI and EI in both groups were significantly decreased compared to those before treatment (all P<0.05); UI and EI in the research group were significantly higher than those in control group (all P<0.05). Dry mouth grading in the research group was significantly lower than that in the control group (all P<0.05). After treatment, the levels of related indicators regarding quality of life, local recurrence-free rate, and distant metastasis-free rate in the research group were higher than those in the control group (all P<0.05). CONCLUSION: IMRT for patients with NPC can significantly improve short-term response rate, reduce mouth dryness and parotid gland injury after radiotherapy, enhance quality of life, and facilitate the prognosis of patients.
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Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1-4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyses the synthesis of cyclic GMP-AMP (cGAMP)9-12, which stimulates the induction of type I interferons through the STING-TBK1-IRF-3 signalling axis13-15. STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase8,16. The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK18,17-20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons21. However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNß after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders.
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Secuencias de Aminoácidos , Secuencia Conservada , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Cristalografía por Rayos X , Activación Enzimática , Células HEK293 , Humanos , Interferón beta/metabolismo , Proteínas de la Membrana/genética , Modelos Moleculares , Mutación , Nucleótidos Cíclicos/metabolismo , Unión Proteica , Transducción de SeñalRESUMEN
BACKGROUND: Gray matter (GM) damage after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients can result in cognitive impairment, while there may be no visible brain tissue change according to the conventional magnetic resonance imaging (MRI). This study investigated radiation-induced GM volume differences between NPC patients who received RT and those who did not. METHODS: High-resolution brain structural MRI data from two groups of patients were acquired. The pre-RT group was composed of 56 newly diagnosed but not yet medically treated NPC patients, while the after-RT group consisted of 40 NPC patients who had completed RT more than 1 year ago. Voxel-based morphometry (VBM) was applied to assess GM volumes. Two sample t-test was used to analyze GM volumes voxel-by-voxel using the VBM8 toolbox built in the SPM software. Radiation-induced cortical volume alteration in all NPC patients after RT and dosimetry of 36 patients were analyzed. RESULTS: Compared to pre-treatment group, cortical volumes of GM were significantly smaller in the left hippocampus, the right pulvinar and the right middle temporal gyrus (MTG, P<0.001, AlphaSim correction, cluster size ≥157). The mean dose (Dmean) for bilateral hippocampal heads were significantly higher than other different parts of the brain (P<0.001). No significant correlations between the GM volume in any brain regions and the mean dose of corresponding position of these brain regions were observed (P>0.05). CONCLUSIONS: Radiation to the NPC patients can not only induce damage of the hippocampus, but also other secondary damages of GM.
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Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.
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Proteínas de la Cápside/inmunología , Proteínas Asociadas a Matriz Nuclear/inmunología , Proteínas Asociadas a Matriz Nuclear/fisiología , Factores de Transcripción de Octámeros/inmunología , Factores de Transcripción de Octámeros/fisiología , Proteínas de Unión al ARN/inmunología , Proteínas de Unión al ARN/fisiología , Cápside/metabolismo , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/fisiología , Núcleo Celular/metabolismo , ADN Viral/genética , ADN Viral/inmunología , Proteínas de Unión al ADN , Células Dendríticas/inmunología , Infecciones por VIH/inmunología , VIH-1/genética , VIH-1/inmunología , VIH-2/genética , VIH-2/inmunología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata/inmunología , Macrófagos/inmunología , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Matriz Nuclear/metabolismo , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/fisiología , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/inmunologíaRESUMEN
BACKGROUND The aim of this study was to investigate the efficacy and safety of chemotherapy (CT) combined with stereotactic radiotherapy (SRT) in the treatment of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS A total of 329 NPC patients without any previous treatment were included in this study between January 2009 and November 2013. These patients were divided into three groups: CT group (n=114), SRT group (n=109), and CT + SRT group (n=106). Contrast-enhanced nasopharyngeal computed tomography (CT)/magnetic resonance (MR) scan was performed on the third month after treatment. Short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was graded according to the Acute Radiation Morbidity Scoring Criteria (RTOG) and the World Health Organization (WHO) toxicity grading scale. Overall survival (OS), progression free survival (PFS), and incidence rate of acute toxicity (grade ≥3) were calculated after a 24 month follow-up. RESULTS Total response rate of all patients was 85.41%. Compared with the CT group and the SRT group, the CT + SRT group showed a substantially improved efficacy in NPC treatment. The incidence rate of the acute toxicity in the CT + SRT group was slightly higher than in the CT group and the SRT group, but the difference was not statistically significant. No treatment-related deaths were observed. The CT + SRT group had the highest two-year OS and PFS, followed by the CT group and the SRT group. CONCLUSIONS It was shown that NPC patients treated with CT + SRT had better short- and long-term efficacy than those treated with CT or SRT alone.
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Carcinoma/terapia , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Radiocirugia/métodos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Quimioterapia/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.
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Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismo , Virus Zika/metabolismo , Cristalografía por Rayos X , Metiltransferasas/metabolismo , Conformación Proteica , Caperuzas de ARN , ARN Polimerasa Dependiente del ARN/metabolismo , Especificidad por Sustrato , Replicación Viral , Virus Zika/fisiologíaRESUMEN
PURPOSE: Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. METHODS: Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11C-N-methylspiperone (11C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). RESULTS: Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. CONCLUSION: Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.
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Mapeo Encefálico , Imagen por Resonancia Magnética , Imagen Multimodal , Música , Tomografía Computarizada por Rayos X , Adulto , Radioisótopos de Carbono , Emociones , Voluntarios Sanos , Humanos , Masculino , Espiperona/análogos & derivados , Adulto JovenRESUMEN
Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-ß) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses.
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Factor 3 Regulador del Interferón/química , Rotavirus/química , Proteínas no Estructurales Virales/química , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Adaptadoras del Transporte Vesicular/química , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/inmunología , Secuencias de Aminoácidos , Proteína de Unión a CREB/química , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/inmunología , Humanos , Evasión Inmune , Inmunidad Innata , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/inmunología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Dominios Proteicos , Rotavirus/genética , Rotavirus/inmunología , Infecciones por Rotavirus/genética , Infecciones por Rotavirus/inmunología , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunologíaRESUMEN
OBJECTIVE: To study the effects of Numb gene expression on radiation sensitivity of nonsmall cell lung cancer (NSCLC) stem cells. MATERIALS AND METHODS: The side population (SP) cells A549-SP were transfected with pcDNA3.1 (pcDNA3.1 group), pcDNA-Numb (pcDNA-Numb group) and shRNA-Numb (shRNA-Numb group). Real-time quantitative polymerase chain reaction and Western blot were performed to determine Numb expression; MTT method was used to measure the proliferation activity change of the NSCLC stem cells both before and after irradiation with different doses of 60Coγ ray; Hoechst staining and Annexin V-FITC/PI were used to detect the apoptosis of the NSCLC stem cells; and colony-forming assay was used to determine the effect of Numb expression on radiation sensitivity of the NSCLC stem cells. RESULTS: Increased mRNA and protein expressions of the A549-SP cells were found in the pcDNA-Numb group, and decreased mRNA and protein expressions were found in the shRNA-Numb group. The optical density value of the cells decreased in the pcDNA-Numb group but increased in the shRNA-Numb group. The cells with over-expressed Numb showed obvious nuclear condensation and fragmentation; the apoptosis rate increased significantly. The cells with knockdown Numb showed less nuclear damage; the apoptosis rate significantly decreased. After irradiation, the cells in the pcDNA-Numb group showed decreased survival rate, clonality, and the values of D0, Dq, N, and SF2; whereas the cells in the shRNA-Numb group showed the opposite trend. CONCLUSIONS: Radiation sensitivity of NSCLC stem cells was enhanced with the increase of Numb expression. Determination of Numb expression helped to evaluate the response of lung cancer to radiotherapy, which was important for guiding tumor treatment clinically.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Apoptosis/genética , Apoptosis/efectos de la radiación , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/efectos de la radiación , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/metabolismo , Células Madre Neoplásicas/efectos de la radiación , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Tolerancia a Radiación , TransfecciónRESUMEN
Distance effect has been regarded as the best established marker of basic numerical magnitude processes and is related to individual mathematical abilities. A larger behavioral distance effect is suggested to be concomitant with lower mathematical achievement in children. However, the relationship between distance effect and superior mathematical abilities is unclear. One could get superior mathematical abilities by acquiring the skill of abacus-based mental calculation (AMC), which can be used to solve calculation problems with exceptional speed and high accuracy. In the current study, we explore the relationship between distance effect and superior mathematical abilities by examining whether and how the AMC training modifies numerical magnitude processing. Thus, mathematical competencies were tested in 18 abacus-trained children (who accepted the AMC training) and 18 non-trained children. Electroencephalography (EEG) waveforms were recorded when these children executed numerical comparison tasks in both Arabic digit and dot array forms. We found that: (a) the abacus-trained group had superior mathematical abilities than their peers; (b) distance effects were found both in behavioral results and on EEG waveforms; (c) the distance effect size of the average amplitude on the late negative-going component was different between groups in the digit task, with a larger effect size for abacus-trained children; (d) both the behavioral and EEG distance effects were modulated by the notation. These results revealed that the neural substrates of magnitude processing were modified by AMC training, and suggested that the mechanism of the representation of numerical magnitude for children with superior mathematical abilities was different from their peers. In addition, the results provide evidence for a view of non-abstract numerical representation.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Conceptos Matemáticos , Red Nerviosa/fisiología , Solución de Problemas/fisiología , Análisis y Desempeño de Tareas , Electroencefalografía/métodos , Femenino , Humanos , MasculinoRESUMEN
This study examined whether long-term abacus-based mental calculation (AMC) training improved numerical processing efficiency and at what stage of information processing the effect appeard. Thirty-three children participated in the study and were randomly assigned to two groups at primary school entry, matched for age, gender and IQ. All children went through the same curriculum except that the abacus group received a 2-h/per week AMC training, while the control group did traditional numerical practice for a similar amount of time. After a 2-year training, they were tested with a numerical Stroop task. Electroencephalographic (EEG) and event related potential (ERP) recording techniques were used to monitor the temporal dynamics during the task. Children were required to determine the numerical magnitude (NC) (NC task) or the physical size (PC task) of two numbers presented simultaneously. In the NC task, the AMC group showed faster response times but similar accuracy compared to the control group. In the PC task, the two groups exhibited the same speed and accuracy. The saliency of numerical information relative to physical information was greater in AMC group. With regards to ERP results, the AMC group displayed congruity effects both in the earlier (N1) and later (N2 and LPC (late positive component) time domain, while the control group only displayed congruity effects for LPC. In the left parietal region, LPC amplitudes were larger for the AMC than the control group. Individual differences for LPC amplitudes over left parietal area showed a positive correlation with RTs in the NC task in both congruent and neutral conditions. After controlling for the N2 amplitude, this correlation also became significant in the incongruent condition. Our results suggest that AMC training can strengthen the relationship between symbolic representation and numerical magnitude so that numerical information processing becomes quicker and automatic in AMC children.
RESUMEN
Abacus-based mental calculation (AMC) is a unique strategy for arithmetic that is based on the mental abacus. AMC experts can solve calculation problems with extraordinarily fast speed and high accuracy. Previous studies have demonstrated that abacus experts showed superior performance and special neural correlates during numerical tasks. However, most of those studies focused on the perception and cognition of Arabic numbers. It remains unclear how the abacus numbers were perceived. By applying a similar enumeration Stroop task, in which participants are presented with a visual display containing two abacus numbers and asked to compare the numerosity of beads that consisted of the abacus number, in the present study we investigated the automatic processing of the numerical value of abacus numbers in abacus-trained children. The results demonstrated a significant congruity effect in the numerosity comparison task for abacus-trained children, in both reaction time and error rate analysis. These results suggested that the numerical value of abacus numbers was perceived automatically by the abacus-trained children after long-term training.
Asunto(s)
Conceptos Matemáticos , Solución de Problemas/fisiología , Niño , Femenino , Humanos , Masculino , Desempeño Psicomotor/fisiología , Test de StroopRESUMEN
BACKGROUND: Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism. METHODS: Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and (11)C-N-methylspiperone ((11)C-NMSP) to assess the availability of D2/5-HT2A receptors and with (18)F-fluoro-D-glucose ((18)F-FDG) to assess regional brain glucose metabolism, a marker of brain function. (11)C-NMSP and (18)F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. RESULTS: In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. CONCLUSIONS: For the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects.
Asunto(s)
Conducta Adictiva/diagnóstico por imagen , Conducta Adictiva/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Internet , Tomografía de Emisión de Positrones , Juegos de Video , Adulto , Conducta Adictiva/metabolismo , Encéfalo/metabolismo , Estudios de Casos y Controles , Glucosa/metabolismo , Humanos , Masculino , Receptores de Dopamina D2/metabolismo , Sinapsis/metabolismo , Adulto JovenRESUMEN
Exact (EX) and approximate (AP) calculations rely on distinct neural circuits. However, the training effect on the neural correlates of EX and AP calculations is largely unknown, especially for the AP calculation. Abacus-based mental calculation (AMC) is a particular arithmetic skill that can be acquired by long-term abacus training. The present study investigated whether and how the abacus training modulates the neural correlates of EX and AP calculations by functional magnetic resonance imaging (fMRI). Neural activations were measured in 20 abacus-trained and 19 nontrained Chinese children during AP and EX calculation tasks. Our results demonstrated that: (1) in nontrained children, similar neural regions were activated in both tasks, while the size of activated regions was larger in AP than those in the EX; (2) in abacus-trained children, no significant difference was found between these two tasks; (3) more visuospatial areas were activated in abacus-trained children under the EX task compared to the nontrained. These results suggested that more visuospatial strategies were used by the nontrained children in the AP task compared to the EX; abacus-trained children adopted a similar strategy in both tasks; after long-term abacus training, children were more inclined to apply a visuospatial strategy during processing EX calculations.