Project description:To investigate effects on mRNA expression through treatment with FG-3019, irradiation and their combination to gain mechanistic hypotheses on the effects of these treatments on glioblastoma stem cell like cells which have been observed in vitro and in vivo. mRNA expression was measured 6 h after treatment with FG-3019, irradiation and their combination. 3 biological replicates were analyzed for each treatment condition (control, FG-3019, irratiation and FG-3019+irradiation)
Project description:Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme beta-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation. In this study we performed microarray analysis of ascending aortas from normal and MPS VII mice, trying to find out possible genes responsible for the phenotype observed. In addition, during our breeding strategy, we noticed that some MPS VII mice had less dilated aortas, and we proposed that an yet-unidentified gene could be responsible for the difference observed. We therefore included in the analysis two MPS VII mice with aortas that were not dilated. Total RNA extracted from ascending aortas from 3 Normal mice, 3 MPS VII mice with dilated aortas and 2 MPS VII mice with aortas that were not dilated.
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
Project description:We used microarray to detect pathway differences in the various brain regions in a monogenic in mucopolysaccharidosis type VII ( MPS VII ), a mouse model of a lysosomal storage disease A number of changes revealed unexpected system and process alterations, such as upregulation of the immune system with few inflammatory changes (a significant difference from the closely related MPS IIIb model), down-regulation of major oligodendrocyte genes even though white matter changes are not a feature histopathologically, and a plethora of developmental gene changes. 94 samples, no replicates, made up of half normals and half MPS mutant mice for the MPS VII mutation backcrossed on a C3h-heouj background
Project description:Transport through the NPC relies on intrinsically disordered FG-Nups forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with nuclear transport receptor Kap95, form a native cytosolic condensate in yeast. In aged cells this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup liquid-liquid phase separation, promoting a liquid-like state. Nsp1’s presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC assembly and transport defects and a general decline in protein quality control, all quantitatively mimicking aging phenotypes. Excitingly, these phenotypes can be rescued by cytosolic Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.