Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of Drosophila wild type vs TIM-MJD mutants expressing a polyglutamine-expanded neurotoxic protein in the major timeless (tim)-expressing cells after 3 days of training in light-dark (LD) conditions

ABSTRACT: WT flies or flies of the strain Tim-gal4; UAS-MJD78Q. All samples were collected at ZT16 after 3 days of training in LD conditions.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Sebastian Kadener

PROVIDER: E-GEOD-2422 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Neurotoxic protein expression reveals connections between the circadian clock and mating behavior in Drosophila.

Kadener Sebastian S Villella Adriana A Kula Elzbieta E Palm Kristyna K Pyza Elzbieta E Botas Juan J Hall Jeffrey C JC Rosbash Michael M

Proceedings of the National Academy of Sciences of the United States of America 20060828 36

To investigate the functions of circadian neurons, we added two strategies to the standard Drosophila behavioral genetics repertoire. The first was to express a polyglutamine-expanded neurotoxic protein (MJDtr78Q; MJD, Machado-Joseph disease) in the major timeless (tim)-expressing cells of the adult brain. These Tim-MJD flies were viable, in contrast to the use of cell-death gene expression for tim neuron inactivation. Moreover, they were more arrhythmic than flies expressing other neurotoxins a ...[more]

PMID: 16938865

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Project description:Exhaustion markers are expressed by T lymphocytes in Follicular Lymphoma (FL). Through these, TIM-3 has been recently identified as a poor pronostic factor when expressed by FL CD4+ T cells. Before this study, there was no molecular characterization of unstimulated CD8+ T cells, expressing - or not - TIM-3. We used microarrays to compare the global gene expression profile between CD8+TIM-3+ T cells and CD8+TIM-3- T cells freshly sorted from follicular lymphoma biopsies. Abstract from the associated publication: Up-regulation of T-cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8+TIM-3+ T cells in lymph nodes of FL patients. When compared to their CD8+TIM-3- counterparts, CD8+TIM-3+ T cells exhibited defective cytokine production following TCR engagement. Furthermore CD8+TIM-3+ T cells display ex vivo markers of lytic granule release and remain unresponsive to further TCR-induced activation of the lytic machinery. Although confocal microscopy showed that TIM-3 expression on CD8+ T cells correlated with minor alterations of immunological synapse, a selective reduction of ERK signaling in CD8+TIM-3+ T cells was observed by phospho-flow analysis. Finally, short relapse free survival despite rituximab(R)-chemotherapy was observed in patients with high content of TIM-3+ cells and a poor infiltrate of granzyme B+ T cells in FL lymph nodes. Together, our data indicate that, besides selective TCR early signaling defects, TIM-3 expression correlates with unresponsiveness of ex vivo CD8+ T cells in FL. They show that scores based on the combination of exhaustion and cytolytic markers in FL microenvironment might be instrumental to identify patients at early risk of relapses following R-chemotherapy.

Dataset Information

Transcription profiling of Drosophila wild type vs TIM-MJD mutants expressing a polyglutamine-expanded neurotoxic protein in the major timeless (tim)-expressing cells after 3 days of training in light-dark (LD) conditions

Publications

Neurotoxic protein expression reveals connections between the circadian clock and mating behavior in Drosophila.

Similar Datasets

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