Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ.
Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.
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View SamplesRHAU (RNA helicase-associated with AU-rich element) is a DExH protein that was originally identified as a factor accelerating AU-rich element-mediated mRNA degradation. The finding that RHAU is predominantly localized in the nucleus, despite that mRNA degradation occurs in cytoplasm, prompted us to consider nuclear functions of RHAU. In HeLa cells, RHAU was localized throughout the nucleoplasm with some concentration in nuclear speckles in a manner dependent on ATPase activity. Transcriptional arrest altered its localization to nucleolar caps where it was colocalized with other RNA helicases, p68 and p72, suggesting that RHAU is involved in transcription-related RNA metabolism in the nucleus. To see whether RHAU affects global gene expression either transcriptionally or posttranscriptionally, we performed microarray analysis using total RNA prepared from RHAU-depleted HeLa cell lines, measuring both steady-state mRNA levels and mRNA half-lives by ActinomycinD-chase. We found that most transcripts whose steady-state levels were affected by RHAU knockdown did not show changes in their half-lives, suggesting the involvement of transcriptional regulation for these transcripts. We propose that RHAU has dual functions involved in synthesis and degradation of mRNA in different subcellular compartments.
Transcription-dependent nucleolar cap localization and possible nuclear function of DExH RNA helicase RHAU.
Sex
View SamplesWe performed the oligonucleotide microarray analysis in bipolar disorder, major depression, schizophrenia, and control subjects using postmortem prefrontal cortices provided by the Stanley Foundation Brain Collection. By comparing the gene expression profiles of similar but distinctive mental disorders, we explored the uniqueness of bipolar disorder and its similarity to other mental disorders at the molecular level. Notably, most of the altered gene expressions in each disease were not shared by one another, suggesting the molecular distinctiveness of these mental disorders. We found a tendency of downregulation of the genes encoding receptor, channels or transporters, and upregulation of the genes encoding stress response proteins or molecular chaperons in bipolar disorder. Altered expressions in bipolar disorder shared by other mental disorders mainly consisted of upregulation of the genes encoding proteins for transcription or translation. The genes identified in this study would be useful for the understanding of the pathophysiology of bipolar disorder, as well as the common pathophysiological background in major mental disorders at the molecular level.
Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders.
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View SamplesAnalysis of sol2 mutant. SOL2 protein is a receptor-like kinase
The receptor-like kinase SOL2 mediates CLE signaling in Arabidopsis.
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View SamplesBone marrow-derived macrophages derived from C57Bl/6, Myd88-/- and Trif-/-, Ifnar-/-, Atm-/-, Sting-/-, Scid, Irf3-/-, Irf1-/-, p53-/-, Nrf2-/-mice were irradiated with 6Gray ioninzing radiation; C57Bl/6 macrophages were Irradiated in the presence of MAPK inhibitors or Reactive Oxygen Species Scavenger (N-Acetyl Cysteine), Two biological replicates were generated for each time point. RNA samples were collected at 0 (unirradiated), 0.5, 1, 2, 6, and 24h post irradiation except where ever mentioned. Overall design: Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/- and Trif-/-, Ifnar-/-, Atm-/-, Sting-/-, Scid, Irf3-/-, Irf1-/-, p53-/-, Nrf2-/-mice were irradiated with 6Gray ioninzing radiation; C57Bl/6 macrophages were Irradiated in the presence of MAPK inhibitors or Reactive Oxygen Species Scavenger (N-Acetyl Cysteine), Two biological replicates were generated for each time point. RNA samples were collected at 0 (unirradiated), 0.5, 1, 2, 6, and 24h post irradiation except where ever mentioned.
Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation.
Specimen part, Cell line, Subject
View SamplesPlant vascular tissues are essential for the existence of land plants. Many studies have revealed the process underlying the development of vascular tissues. However, the initiation of vascular development is still a mystery. LONESOME HIGHWAY (LHW), which encodes a bHLH transcription factor, is expressed in the initial step of vascular development in roots. LHW and TMO5 LIKE1 (T5L1) interact each other and function as a heterodimer. Here, we identified specific genes downstream of LHW-T5L1 with transformed suspension culture cells in microarray experiments.
A bHLH complex activates vascular cell division via cytokinin action in root apical meristem.
Specimen part, Treatment, Time
View SamplesThe ability to isolate pure pancreatic -cells would greatly aid multiple areas of diabetes research. We developed an exendin-4-like neopeptide conjugate for the rapid purification and isolation of functional pancreatic -cells. By targeting the glucagon-like peptide-1 receptor, -cells were isolated within an hour and were >99% pure. These studies were confirmed by immunostaining, confocal microscopy and microarray analysis on isolated cells. Gene expression profiling studies of the cytofluorometrically sorted -cells provided new insights into the genetic programs at play of different ages and stages during type-1 diabetes development. The described isolation method should have broad applicability to the -cell field.
Rapid, high efficiency isolation of pancreatic ß-cells.
Sex, Age, Specimen part
View SamplesThe behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Gene expression, molecular class changes, and pathway analysis after neoadjuvant systemic therapy for breast cancer.
Specimen part, Disease, Disease stage, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.
Specimen part
View SamplesHuman intelligence demonstrates one of the highest heritabilities among human quantitative traits. Phenotypically discordant monozygotic twins provide a way to identify loci responsible for normal-range intelligence.
Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.
Specimen part
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