RESUMO
Genome-wide mapping approaches in diverse populations are powerful tools to unravel the genetic architecture of complex traits. The main goals of our study were to investigate the potential and limits to unravel the genetic architecture and to identify the factors determining the accuracy of prediction of the genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) based on data collected with a diverse panel of 372 European varieties. The wheat lines were phenotyped in multi-location field trials for FHB resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide association mapping in combination with fivefold cross-validations and observed surprisingly high accuracies of prediction for marker-assisted selection based on the detected quantitative trait loci (QTLs). Using a random sample of markers not selected for marker-trait associations revealed only a slight decrease in prediction accuracy compared with marker-based selection exploiting the QTL information. The same picture was confirmed in a simulation study, suggesting that relatedness is a main driver of the accuracy of prediction in marker-assisted selection of FHB resistance. When the accuracy of prediction of three genomic selection models was contrasted for the three marker data sets, no significant differences in accuracies among marker platforms and genomic selection models were observed. Marker density impacted the accuracy of prediction only marginally. Consequently, genomic selection of FHB resistance can be implemented most cost-efficiently based on low- to medium-density SNP arrays.
Assuntos
Resistência à Doença/genética , Fusarium , Locos de Características Quantitativas , Triticum/genética , Cruzamento , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Modelos Lineares , Repetições de Microssatélites , Modelos Genéticos , Fenótipo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único , Seleção Genética , Triticum/microbiologiaRESUMO
Neuregulin (NRG)/ErbB receptor signaling pathways have recently been implicated in the reversal of long-term potentiation at hippocampal glutamatergic synapses. Moreover, polymorphisms in NRG-1 and ErbB-4 genes have been linked to an increased risk for developing schizophrenia. ErbB-4 is highly expressed at glutamatergic synapses where it binds to PSD-95 via its carboxyl terminal T-V-V sequence. Here we investigated the expression, localization and trafficking of ErbB-4 in cultured hippocampal neurons by immunocytochemistry, surface protein biotinylation, and live labeling of native receptors. We show that neuronal ErbB-4 is detected at its highest levels in GABAergic interneurons, as observed in vivo. ErbB-4 immunoreactivity precedes PSD-95 expression, with ErbB-4 cluster initially forming in the absence of, but later associating with, PSD-95-positive puncta. By surface protein biotinylation, the fraction of ErbB-4 receptors on the plasma membrane increases from 30% to 65% between 6 and 16 days in vitro (DIV). Interestingly, 30 min of NRG stimulation triggers measurable ErbB-4 receptor internalization at DIV 16, despite increased colocalization with PSD-95. We also investigated the role of TNFalpha-converting enzyme (TACE)-mediated receptor processing in regulating ErbB-4 surface expression. We found that the cleavage-resistant JM-b isoform accounts for 80% of all ErbB-4 transcripts in cultured hippocampal neurons. Receptor stimulation or treatment with phorbol esters does not induce detectable ErbB-4 processing, indicating that neurons mostly rely on endocytosis of the intact receptor to regulate ErbB-4 surface expression. These results enhance our understanding of the regulation of ErbB-4--mediated signaling at glutamatergic synapses.
Assuntos
Endocitose/fisiologia , Receptores ErbB/metabolismo , Hipocampo/citologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Isoformas de Proteínas/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Células Cultivadas , Proteína 4 Homóloga a Disks-Large , Receptores ErbB/genética , Guanilato Quinases , Humanos , Interneurônios/citologia , Interneurônios/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/genética , Neuregulina-1 , Neurônios/química , Neurônios/citologia , Isoformas de Proteínas/genética , Ratos , Ratos Sprague-Dawley , Receptor ErbB-4 , Transdução de Sinais/fisiologiaAssuntos
Neoplasias Torácicas/cirurgia , Toracoplastia/métodos , Neoplasias Ósseas/cirurgia , Neoplasias da Mama/cirurgia , Carcinoma Broncogênico/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia/cirurgia , Osteossarcoma/cirurgia , Costelas/cirurgia , Sarcoma/cirurgia , Esterno/cirurgia , Retalhos CirúrgicosRESUMO
This procedure is efficient, inexpensive and technically easy to perform. It can be used for fractures and pseudoarthroses of the femur and tibia.