RESUMEN
Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.
Asunto(s)
Movimiento Celular , Proteína 1 Similar a ELAV/fisiología , Neuronas/fisiología , ARN Mensajero/metabolismo , Animales , Tipificación del Cuerpo/genética , Movimiento Celular/genética , Células Cultivadas , Embrión de Mamíferos , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células-Madre Neurales/fisiología , Neurogénesis/genética , Embarazo , Profilinas/fisiología , Procesamiento Postranscripcional del ARN/genéticaRESUMEN
Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuRflox/flox;Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.
Asunto(s)
Depresión/metabolismo , Proteína 1 Similar a ELAV/metabolismo , Plasticidad Neuronal/fisiología , Corteza Prefrontal/metabolismo , Animales , Depresión/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Restricción Física , Estrés Psicológico/complicacionesRESUMEN
Hospitals need to invest a lot of manpower to manually input the contents of medical invoices (nearly 300,000,000 medical invoices a year) into the medical system. In order to help the hospital save money and stabilize work efficiency, this paper designed a system to complete the complicated work using a Gaussian blur and smoothing-convolutional neural network combined with a recurrent neural network (GBS-CR) method. Gaussian blur and smoothing (GBS) is a novel preprocessing method that can fix the breakpoint font in medical invoices. The combination of convolutional neural network (CNN) and recurrent neural network (RNN) was used to raise the recognition rate of the breakpoint font in medical invoices. RNN was designed to be the semantic revision module. In the aspect of image preprocessing, Gaussian blur and smoothing were used to fix the breakpoint font. In the period of making the self-built dataset, a certain proportion of the breakpoint font (the font of breakpoint is 3, the original font is 7) was added, in this paper, so as to optimize the Alexnet-Adam-CNN (AA-CNN) model, which is more suitable for the recognition of the breakpoint font than the traditional CNN model. In terms of the identification methods, we not only adopted the optimized AA-CNN for identification, but also combined RNN to carry out the semantic revisions of the identified results of CNN, meanwhile further improving the recognition rate of the medical invoices. The experimental results show that compared with the state-of-art invoice recognition method, the method presented in this paper has an average increase of 10 to 15 percentage points in recognition rate.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Algoritmos , Humanos , Distribución Normal , SemánticaRESUMEN
One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
RESUMEN
The hydrazone compound N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide (H2L) was prepared. With H2L and copper acetate a new copper complex [Cu(HL)(NCS)]·CH3OH was synthesized. Both the hydrazone and the copper complex were characterized by physico-chemical methods and single crystal X-ray diffraction techniques. The complex is a thiocyanato-coordinated copper(II) species. The Cu atom in the complex is in square planar geometry. The complex is a promising urease inhibitor.
Asunto(s)
Complejos de Coordinación/química , Inhibidores Enzimáticos/química , Hidrazinas/química , Ureasa/antagonistas & inhibidores , Complejos de Coordinación/síntesis química , Cobre/química , Pruebas de Enzimas , Inhibidores Enzimáticos/síntesis química , Hidrazinas/síntesis química , Estructura Molecular , Ureasa/químicaRESUMEN
PURPOSE: To detect the gene expression of miRNAs in patients with periodontitis and to explore their biological functions and involved signaling pathways. METHODS: Bioinformatics analysis of gene chip data from 158 periodontitis patients and 40 healthy controls of the microarray database GSE54710 were performed. The expression changes of miRNAs were analyzed. The involved biological function and signal path was predicted. SPSS 19.0 software package was used for statistical analysis. RESULTS: Five miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917, hsa-miR-671-5p) were significantly up-regulated, and 4 miRNAs (hsa-miR-203, hsa-miR-210, hsa-miR-1246, hsa-miR-1260) were significantly down-regulated. Among them, there were 584 target genes of hsa-miR-1260 and 139 target genes of hsa-miR-451. KEGG pathway enrichment analysis showed that hsa-miR-1260 target gene was significantly enriched into 12 signaling pathways such as TGF-beta, and hsa-miR-451 target gene was significantly enriched into 17 signaling pathways. CONCLUSIONS: miRNAs expression profiles were obtained in periodontitis tissues, periodontitis-induced hsa-miR-1260 and hsa-miR-451 may play a key role in the pathophysiology of periodontitis.
Asunto(s)
MicroARNs , Periodontitis , Biología Computacional , Perfilación de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development.
Asunto(s)
Receptor DCC/metabolismo , Neocórtex/crecimiento & desarrollo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Neuronas/metabolismo , Animales , Animales Recién Nacidos , Movimiento Celular/fisiología , Femenino , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Neocórtex/citología , Neocórtex/metabolismo , Netrina-1/metabolismo , Fosforilación , Dominios Proteicos , Proto-Oncogenes Mas , Proteína ReelinaRESUMEN
OBJECTIVE: To evaluate the expression and clinical significance of tumor necrosis factor receptor (TNFR) superfamily protein CD30 in diffuse large B cell lymhoma (DLBCL). METHODS: The CD30 expression, clinical characteristics and prognosis of 63 patients with DLBCL, NOS out of 149 patients with DLBCL admitted in our hospital between January 2008 and December 2012 were analyzed retrospectively. RESULTS: no significant relationship existed between CD30 expression and clinical features, such as age, sex, B symptoms, staging, ECOG PS, LDH level, extranodal site involvement, IPI, GCB or non GCB type, bone marrow involvement. By univariate analysis, the clinical factors associated with general OS and EFS, included CD30, ECOG PS, B symptoms, extranodal site involvement, LDH level, IPI, bone marrow involvement and rituximab. Univariate analysis in GCB DLBCL indicated that CD30 had no significant effect on OS and EFS. However, univariate analysis in non-GCB DLBCL indicated CD30 was associated with longer OS (P=0.037) and showed a tendency of better EFS (P=0.067). In multivariate analysis, IPI and CD30 were independent prognostic factors for OS (IPI: P=0.000, 95%CI 0.042-0.374, CD30: P=0.044, 95%CI 1.055-60.613), and IPI also was independent prognostic factors for EFS (P=0.000, 95%CI 0.040-0.360). CD30+ and DLBCL have a tendency of better EFS (P=0.050, 95%CI 0.996-56.501). CONCLUSION: CD30 expression level correlates with the prognosis of DLBCL and has a certain clinical value, which may be a new prognostic index of DLBCL.
Asunto(s)
Antígeno Ki-1/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
To study the features and ecological risk of PAHs in surface water from Yangtze River, 19 water samples were collected from the main stream and branch of Yangtze River in August 2015. Solid phase extraction method was used to extract PAHs, and the concentrations of the 16 priority PAHs were determined using GC-MS. The results indicated that the concentration of total PAHs (∑PAHs) in the surface water ranged from 17.7-110 ng·L-1 with an average value of 42.6 ng·L-1. The predominant PAHs in the water were PAHs with 2-3 rings, accounting for 67.7% of ∑PAHs. The results of molecular diagnostic ratios indicated that the origin of PAHs was mostly combustion sources, including fossil fuel and biomass combustion. PMF model was used to quantitatively acquire the source contribution of PAHs, which indicated that four sources were identified and their contribution rates were respectively biomass and coal combustion (40.1%), petroleum source (19.6%), traffic source (17.5%) and coke oven source (22.8%). The results of ecological risk assessment indicated that PAHs with 2-3 rings had a relatively high risk level, and Wujiang station and lower reach had a relatively high risk level based on risk quotient. Overall, the ecological risk of PAHs in the Yangtze River was at a relatively low level.