Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat. Overall design: RNA-seq on Drosophila head samples fed control and sucralose diet
Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.
Specimen part, Cell line, Subject
View SamplesThere is some emerging evidence that members of the Schlafen (SLFN) family of proteins mediate antineoplastic responses, but the mechanisms accounting for these effects are not known. We provide evidence that human SLFN5, an interferon (IFN)- inducible member of the family, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of matrix metalloproteinases (MMP)-1 and -13 and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Overall design: Examination of 2 SLFN5 knockdown cells and 2 controls, in triplicate.
Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells.
No sample metadata fields
View SamplesGlioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis, which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins.
Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.
Sex
View SamplesAbiotic stresses like drought, salinity, high and low temperature, and submergence are major factors that limit the crop productivity. Hence, identification of genes associated with stress response in crops is a prerequisite for improving their tolerance to adverse environmental conditions. In this study, we have analyzed the expression profiles of three genotypes WT, TaVAP mutant and TaVAPOE plants in Arabidopsis thaliana in col-0 background using microarray technology to identify the genes differentially expressed under control conditions.
Gene encoding vesicle-associated membrane protein-associated protein from Triticum aestivum (TaVAP) confers tolerance to drought stress.
Specimen part
View SamplesWe describe a method for isolating RNA suitable for high-throughput RNA sequencing (RNA-seq) from small numbers of fluorescently labeled cells isolated from live zebrafish (Danio rerio) embryos without using costly, commercially available columns. This method ensures high cell viability after dissociation and suspension of cells and gives a very high yield of intact RNA. We demonstrate the utility of our new protocol by isolating RNA from fluorescence activated cell sorted (FAC sorted) pineal complex neurons in wild-type and tbx2b knockdown embryos at 24 hours post fertilization. Tbx2b is a transcription factor required for pineal complex formation. We describe a bioinformatics pipeline used to analyze differential expression following high-throughput sequencing and demonstrate the validity of our results using in situ hybridization of differentially expressed transcripts. This protocol brings modern transcriptome analysis to the study of small cell populations in zebrafish. Overall design: Differential expression analysis of mRNA levels in a single time-point (24 hpf) between wild-type and Tbx2b deficient FAC sorted pineal complex cells
Identification of differentially expressed genes during development of the zebrafish pineal complex using RNA sequencing.
No sample metadata fields
View SamplesRice transgenic plants of the F-box encoding gene, OsFBK1, in the Pusa Basmati 1 (PB1) variety have been found to display differences in the anther and root phenotypes. In order to elucidate changes at the transcriptome level, microarray of the roots of 14-day-old seedlings of over-expresseion (OE) and knock-down (KD) lines along with vector control (VC) and wild type (WT) were carried out.
The OsFBK1 E3 Ligase Subunit Affects Anther and Root Secondary Cell Wall Thickenings by Mediating Turnover of a Cinnamoyl-CoA Reductase.
Specimen part
View SamplesIndica rice seedlings of IR64 variety were grown hydroponically for 7-days in a culture room with a daily photoperiodic cycle of 14h light and 10h dark. Seedlings were incubated in 0.1% dimethyl sulfoxide (control) or 50 micromolar solutions of indole-3-acetic acid (IAA treatment) and benzyl aminopurine (BAP treatment) for 1h and 3h. Equal amounts of 1h and 3h samoles were pooled for each treatment before RNA isolation. The 5 micrograms of each total RNA sample was processed for microarray analysis according to Affymetrix protocol.
Transcript profiling reveals diverse roles of auxin-responsive genes during reproductive development and abiotic stress in rice.
Specimen part
View SamplesRice transgenic plants of the bZIP encoding gene, OsbZIP48, in the Pusa Basmati 1 (PB1) variety have been found to display differences in the total height. In order to elucidate changes at the transcriptome level, microarray of the 10-day-old seedlings of over-expresseion (OE) and knock-down (KD) lines along with vector control (VC) were carried out.
OsbZIP48, a HY5 Transcription Factor Ortholog, Exerts Pleiotropic Effects in Light-Regulated Development.
Age, Specimen part
View Samples10-day-old wild-type and homozygous transgenic Arabidopsis seedlings (overexpressing OsTOP6A3 and OsTOP6B) grown under normal growth conditions were used for total RNA isolation. The 5 micrograms of each total RNA sample was processed for microarray analysis according to Affymetrix protocol.
Overexpression of putative topoisomerase 6 genes from rice confers stress tolerance in transgenic Arabidopsis plants.
Specimen part
View Samples10-day-old wild-type and homozygous transgenic Arabidopsis seedlings (overexpressing rice topoisomerase 6 subunit A1; OsTOP6A1) grown under normal growth conditions were used for total RNA isolation. The 5 micrograms of each total RNA sample was processed for microarray analysis according to Affymetrix protocol.
Constitutive expression of a meiotic recombination protein gene homolog, OsTOP6A1, from rice confers abiotic stress tolerance in transgenic Arabidopsis plants.
Specimen part
View Samples