Despite the importance of amino acids as basic components of proteins, amino acids also serve as substrates for multiple other metabolic pathways, such as the TCA cycle that regulates energy homeostasis. The response to deficiency in the biosynthesis of specific amino acids (also termed “amino acid starvation”) has been studied extensively in yeast (See for example Petti et. al., 2011 Survival of starving yeast is correlated with oxidative stress response and non-respiratory mitochondria function. Proc. Natl. Acad. Sci. USA 108: 1089-1098). In contrast, very little is known about the metabolic responses to deficiency in the biosynthesis of amino acids in plants. A number of recent reports have already shown that catabolism of amino acids can significantly contribute to cellular energy homeostasis particularly during the nighttime and particularly in response to stress. In the present manuscript we used a previously characterized Arabidopsis mutant with reduced expression of the Lys biosynthesis enzyme L,L-diaminopimelate aminotransferase (dapat) to investigate the physiological and metabolic impacts of deficient Lys biosynthesis. The results obtained demonstrate that not stomatal limitations but rather biochemical alterations are responsible for the decreased photosynthesis and growth of the dapat mutants which mimic stress conditions associated to Lys deficiency. Our findings suggest that manipulation of Lys biosynthesis in dapat mutant simulates a stress response culminating in a highly exquisite metabolic reprogramming such that alternative substrates support energy generation once carbohydrate metabolism is down-regulated.
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Age, Specimen part
View SamplesComparative genomic analysis of nutrient response to NO3-, NH4+ or NH4+: NO3- in barley
Global transcriptional and physiological responses of Saccharomyces cerevisiae to ammonium, L-alanine, or L-glutamine limitation.
Age, Specimen part, Subject, Compound
View SamplesBiP overexpression confers resistance to drought, through an as yet unknown mechanism that is related to ER functioning, has been described that the delay in leaf senescence by BiP overexpression might relate to the absence of the response to drought.
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Specimen part
View SamplesPreterm birth (PTB), defined as the delivery of an infant before 37 weeks of completed gestation, results of the interaction of both, genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the multiple causes of PTB and the numerous maternal and foetal gestational tissues that must interact to facilitate parturition. A common pathway of labour and PTB may be the activation of fetal membranes. In this work chorioamnion membranes from severe preterm and term fetus were analysed using RNA seq. The primary goal of this study was to identify differentially expressed transcripts and dilucidate molecular mechanisms distinguishing severe PTBs from term births. Overall design: Chorioamnion tissues were collected immediately after labor from women who had spontaneous severe preterm births between 24-33 weeks (n=4) and women with spontaneous term labor (>37 weeks)(n=4).
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Sex, Age, Specimen part, Disease stage
View SamplesDuring the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance.
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No sample metadata fields
View SamplesThe prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation.
Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes.
Specimen part
View SamplesPlasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors responsible for hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2 but not Dectin-1 participates in hyphal recognition by pDCs and that Dectin-2 acts in cooperation with the FcR chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. Thus, these structures closely resembled those of neutrophil extracellular traps (NETs). Microarray analysis of the pDC transcriptome upon A. fumigatus infection demonstrated up-regulated expression of genes previously associated with viral infections or apoptosis. Moreover, the abundant expression of type I Interferon-encoding genes seen in CpG-stimulated pDCs was absent in the pDCs infected with A. fumigatus hyphae. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2. This interaction leads to formation of pET and triggers a distinct pattern of pDC gene expression.
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Specimen part
View SamplesAvian pathogenic Escherichia coli strains frequently cause extra-intestinal infections and are responsible for significant economic losses in the poultry industry worldwide. APEC isolates are closely related to human extraintestinal pathogenic E.coli strains and may also act as pathogens for humans. In this work, three type VI secretion systems were deleted to analyze which pathogenicity characteristics would change in the mutants, compared to wild type strain (SEPT 362).
The type VI secretion system plays a role in type 1 fimbria expression and pathogenesis of an avian pathogenic Escherichia coli strain.
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View SamplesCancer cells were MACS sorted from tumor tissue specimem 05-179. Self replicates of CD26+ cancer cells were generated and the expression profiles were determined using Affymetrix U133 Plus 2.0 arrays. These data represent cancer cell type specific transcriptome.
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Specimen part
View SamplesHER-2 positive breast cancers frequently sustain elevated AKT/mammalian target rapamycin (mTOR) signaling which has been associated with resistance to doxorubicin treatment in the clinic. In our study we investigated if the mTOR inhibitor rapamycin increased the sensitivity to doxorubicin therapy in HB4a, a luminal normal mammary cell line; C5.2, a transformed cell derived from HB4a transfected with HER-2 and SKBR3 that exhibits HER-2 amplification. Flow cytometry analysis showed that the combination treatment for 24 hours with rapamycin 20nM and doxorubicin caused accumulation of HB4a and C5.2 cells in S-G2/M. Otherwise in SKBR3 cells, we observed a relative depletion of cells in S-G2/M and concomitant accumulation in G0/G1 of 10% of the cells. The analysis of IC50 of doxorubicin alone and in combination with rapamycin indicated that the sensitivity was increased 2.37 fold in HB4a, 2.46 in C5.2 and 1.87 in SKBR3, suggesting that rapamycin might have enhanced the effects of doxorubicin. Changes in gene expression resulting from co-treatment demonstrated that functional groups of genes with roles in cell cycle, proliferation, apoptosis regulation were represented in the 3 cells analysed. Other biological functions were exclusively associated with each cell suggesting that the inhibition of mTOR activation induced by HER-2 is complex and depends on the cellular context.
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Specimen part, Cell line
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