The crucian carp, Carassius carassius, survives months without oxygen. During anoxia it needs to keep energy expenditure low, particularly in the brain, with its high rate of ATP use related to neuronal activity. This could be accomplished by reducing neuronal excitability through altered expression of genes involved in excitatory neurotransmission. Through cloning and the use of a recently developed real-time RT-PCR approach, with an external RNA control for normalization, we investigated the effect of 1 and 7 days of anoxia (12 degrees C) on the expression of 29 genes, including 8 3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits, 6 N-methyl-d-aspartate (NMDA) receptor subunits, 7 voltage-gated sodium and calcium channels, 4 glutamate transporters, and 4 genes involved in NMDA receptor-mediated neuroplasticity. The subunits of the majority of the gene families had expression profiles similar to those observed in the mammalian brain and showed remarkably stable expression during anoxia. This suggests that the genes may have similar functions in crucian carp and mammals, and that the excitatory abilities of the crucian carp brain are retained during anoxia. Although the data generally argue against profound neural depression ("channel arrest"), NMDA receptor subunit (NR) expression showed features that could mediate reduced neural excitability. Primarily, the NR2 subunit expression, which was dominated by NR2B and NR2D, resembled that seen in hypoxia-tolerant neonatal rats, and decreased anoxic expression of NR1, NR2C, and NR3A indicated reduced numbers of functional NMDA receptors. We also report the full-length sequence of crucian carp NR1 mRNA and a novel NR1 splice cassette introducing an N-glycosylation site into the extracellular S1S2 domain.

Abstract Background Despite maximal therapy with surgery, chemotherapy and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relate to failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multi-omics approach using transcriptomics, proteomics and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxina (synaptogenesis) and afatinib (ERBB4 signalling). Afatinib is currently in clinical trials for GBM. Conclusions Large variation on all omics levels exist between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multi-omics approach offers potential to identify affected pathways on the individual patient level and select treatment options.

In all, 166 genes were differentially expressed; 39 of these were previously defined as inflammatory and considered important for nasal polyposis. The connectivity of all differentially expressed genes was analysed using the PubGene literature co-citation network. Seventy-four of the 166 genes were connected to other genes. By contrast, the average number of connected genes among 100 sets of 166 randomly chosen genes was 31.5. A small number of the differentially expressed genes were highly connected, while most genes had few or no connections. This indicated a scale-free network. The most connected gene was interleukin-8, an inflammatory gene of known importance for nasal polyposis. Twenty-eight of the 74 connected genes were inflammatory (38%), compared with 11 of the 92 unconnected genes (12%), p < 0.0001. Since most evidence suggests that nasal polyps are inflammatory in their nature, this supports the hypothesis that connected genes have more disease relevance than unconnected genes.