C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Specimen part, Treatment
View SamplesDuring low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. During deacclimation in response to warm temperatures cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation. Here, we report metabolic (GC-MS) and transcriptional (microarrays, qRT-PCR) responses underlying deacclimation during the first 24 h after a shift of cold acclimated Arabidopsis thaliana (Columbia-0) plants to warm temperature. The data revealed a faster response of the transcriptome than of the metabolome and provided evidence for tightly regulated temporal responses at both levels. Metabolically deacclimation is associated with decreasing contents of sugars, amino acids and glycolytic and TCA cycle intermediates, indicating an increased need for carbon sources and respiratory energy production associated with growth resumption under warm temperature conditions. Deacclimation also involves extensive down-regulation of protein synthesis and changes in the metabolism of lipids and cell wall components. Altered hormonal regulation appears particularly important during deacclimation, with changes in the expression of genes related to auxin, gibberellin, brassinosteroid, jasmonate and ethylene metabolisms. Several transcription factor families controlling fundamental aspects of plant development are significantly regulated during deacclimation, emphasizing that loss of freezing tolerance and growth resumption are interrelated processes that are transcriptionally highly interrelated. Expression patterns of some clock oscillator components during deacclimation resembled those under warm conditions, indicating at least partial re-activation of the circadian clock. This study provide the first comprehensive analysis of the regulation of deacclimation in cold acclimated plants. The data indicate cascades of rapidly regulated genes and metabolites that underly the developmental switch resulting in reduced freezing tolerance and the resumption of growth. They constitute a reference dataset of genes, metabolites and pathways that are crucial during the first rapid phase of deacclimation and will be useful for the further analysis of this important but under-researched plant process.
Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana.
Specimen part, Treatment
View SamplesChronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for LOH and sub-chromosomal copy loss on chromosome 13 in DNA from FACS-sorted CD19+ cells and paired buccal cells using the Affymetrix XbaI 50K SNP-array platform. The resulting high-resolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and Q-PCR-based expression analysis of selected genes support the following conclusions: i) del13q14 is heterogeneous and composed of multiple subtypes with deletion of Rb or the miR15a/16 loci serving as anatomic landmarks, respectively ii) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/16 cluster to a newly identified telomeric breakpoint cluster at ~50.2-50.5 Mb physical position iii) LATS2 RNA levels are ~2.6-2.8-fold lower in cases with del13q14 type I that do not delete Rb as opposed to all other CLL cases and iv) ~15% of CLL cases display marked reductions in miR15a/16 expression often but not invariably associated with bi-allelic miR15a/16 loss. This data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes including investigations into LATS2 as one of the genes found deregulated as part of del13q14.
Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14.
No sample metadata fields
View SamplesAssess the efficacy of trabectedin in two DLBCL cell lines
Trabectedin is a novel chemotherapy agent for diffuse large B cell lymphoma.
Treatment, Time
View SamplesUnder various pathophysiological muscle-wasting conditions like diabetes and starvation, a family of ubiquitin ligases, including MuRF1 (Muscle specific RING-Finger protein 1), are induced to target muscle proteins for degradation via ubiquitination. In an attempt to identify the in vivo targets of MuRF1 we have generated transgenic mouse lines overexpressing MuRF1 in a skeletal muscle specific fashion. MuRF1-TG lines were viable and had normal fertility. Characterization of their skeletal muscles did not reveal evidence for muscle wasting at 10 weeks of age. In this experiment we compared the skeletal muscle transcriptome of transgenic mice with wildtypes.
MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies.
Sex, Age, Specimen part
View Samples- Background and Aims: Oxygen can fall to low concentrations within plant tissues, either because of environmental factors that decrease the external oxygen concentration or because the movement of oxygen through the plant tissues cannot keep pace with the rate of oxygen consumption. Recent studies document that plants can decrease their oxygen consumption in response to relative small changes in oxygen concentrations to avoid internal anoxia. The molecular mechanisms underlying this response have not been identified yet. The aim of this study was to use transcript and metabolite profiling to investigate the genomic response of Arabidopsis roots to a mild decrease in oxygen concentrations.
Transcript and metabolite profiling of the adaptive response to mild decreases in oxygen concentration in the roots of arabidopsis plants.
No sample metadata fields
View SamplesPurpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized.
A pathobiological role of the insulin receptor in chronic lymphocytic leukemia.
Specimen part
View SamplesAlthough recent evidence suggests that overlapping sense/antisense transcription is a common feature in higher eukaryotes, the possibility that overlapping transcripts could interact to each other and bear a specific biological function has not been explored. Here we show that a plethora of sense/antisense transcript pairs are co-expressed from 8q24.21 within the same cell and acquire a stable double-stranded RNA conformation. Interestingly, these molecules display predominantly nuclear localization and establish specific interactions with nuclear components. A detailed characterization of a particular sense/antisense pair (ndsRNA-2a) revealed that this molecule displays differential localization throughout the cell cycle, interacts with RCC1 and RAN and through the latter with the mitotic RANGAP1-SUMO1/RANBP2 complex. Notably, an increased number of bi/multi-nucleated cells and chromatin bridges were observed upon ndsRNA-2a overexpression, whereas strand-specific ndsRNA-2a knockdown leads to mitotic catastrophe and cell death. This suggests a functional role of ndsRNA-2a in cell cycle progression that critically requires its double stranded nature. Finally, the identification of hundreds of sense/antisense transcripts pairs harboring ndsRNA profile signatures and their regulation by cellular cues suggests that ndsRNAs constitute a novel class of regulatory molecules that are likely to be involved in a plethora of biological processes. Overall design: PLB985 long (3x datasets) and small (3x datasets) strand specific RNA-Seq for captured RNAs. Global PLB985 for long (2x datasets) and small RNAs (2x datasets). Global libraries for EtOH (vehicle) treated (1x dataset) or retinoic acid induced differentiated PLB985 cells (1x dataset).
Human cells contain natural double-stranded RNAs with potential regulatory functions.
No sample metadata fields
View SamplesGene expression analysis of different B-cell chronic lymphoproliferative disorders
Improved classification of leukemic B-cell lymphoproliferative disorders using a transcriptional and genetic classifier.
Specimen part
View SamplesGene expression analyis of primary MCL including IGHV mutated and unmutated cases
Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.
Specimen part, Disease, Disease stage
View Samples