This SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Specimen part, Disease, Disease stage
View SamplesPrimary plasma cell leukaemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinguished from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Here, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequently altered regions were located at 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%) and 17p (35%). A relevant finding of our study was the identification of a minimal biallelical deletion (1.5 Mb) in 8p21.2 encompassing the putative tumor suppressor gene PPP2R2A that was significantly down-regulated in deleted cases. Mutations of TP53 were identified in 4 cases all but one associated with a monoallelic deletion of the gene, whereas activating mutations of BRAF occurred in one case and were absent for N- and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferases activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to our understanding of this particular form of plasma cell dyscrasia and to better elucidate the mechanisms of tumor progression in MM.
Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.
Specimen part, Disease, Disease stage
View SamplesDietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.
Sex, Age, Specimen part
View SamplesUntreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View SamplesFrequent hemodialysis is associated with improvement in myocardial mechanics and cardiac gene expression profile
Impact of frequent nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression.
Age, Specimen part
View SamplesSamples 1-8: Tissue-specific RNA sequencing (Illumina) using dissected ring glands isolated from TWO different time points of control (phm>w1118) third instar larvae. Time points are: light phase zt0-4 (which corresponde to 2-4 hours from second to third instar larvae molt); and dark phase zt18-22 (which corresponde to 16-20 hours from second to third instar larvae molt) Samples 9-32: Tissue-specific gene expression (RNA seq Illumina) using dissected ring glands isolated from TWO different time points of third instar larvae. Genotypes were Timeless-RNAi (phm>tim-RNAi), Period-RNAi (phm>per-RNAi), UAS-TimcDNA (phm>UAS-Tim) and UAS-TimcDNA;UAS-PercDNA (phm>UAS-TimcDNA;UAS-PercDNA). Goal was to identify circadin pathway dependent gene sets in the ring gland. Time points were 2-4 hours and 18-20 hours after L2-L3 molt. Overall design: This study comprises two parts: First, Next generation sequencing was used to determine transcriptional profiles from Drosophila ring glands at ZT0-4 versus ZT18-22 in control larvae. Encore Complete RNA-Seq IL Multiplex System 1-8 (Nugen Part No. 0312) and Encore Complete RNA-Seq IL Multiplex System 9-16 (Nugen Part No. 0313) was used for barcoding and multiplex sequencing. Library prep was based on total RNA isolated from dissected ring glands at two different time points during the third instar (the last larval stage of Drosophila development). Libraries were sequenced on a High-Seq Illumina platform. The second part examined gene expression changes in ring glands where we altered circadian signaling by genetic means. Encore Complete RNA-Seq IL Multiplex System was used to prep the cDNA library from total RNA isolated from ring glands of controls, ring gland-specific Timeless-RNAi (phm>tim-RNAi), Period-RNAi (phm>per-RNAi), UAS-Tim-cDNA (phm>UAS-Tim) and UAS-Tim-cDNA; UAS-Per-cDNA (phm>UAS-Tim-cDNA;UAS-Per-cDNA) larvae at two different time points in the day (ZT0-4 and ZT18-22) for the first three genotypes and exclusively at ZT18-22 for the last two genotypes. Each condition was measured by using two biological samples.
The Circadian Clock Is a Key Driver of Steroid Hormone Production in Drosophila.
Specimen part, Subject
View Samples10 day old seedlings were treated with 5uM of the cytokinin Benzyladenine(BA)or DMSO at 15min, 45min, 120min, 480min and 1440min
Expression profiling of cytokinin action in Arabidopsis.
Age, Compound, Time
View SamplesTreatments that stimulate neuronal excitability enhance motor performance after stroke.cAMP-response-element binding protein (CREB) is a transcription factor that plays a key rolein neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool ofmotor neurons enhances motor recovery after stroke, while blocking CREB signaling preventsstroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with thehM4di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue,demonstrating that it is possible to turn off and on stroke recovery by manipulating theactivity of CREB-transfected neurons. CREB transfection enhances re-mapping of injuredsomatosensory and motor circuits, and induces the formation of new connections withinthese circuits. CREB is a central molecular node in the circuit responses after stroke that leadto recovery from motor deficits.
CREB controls cortical circuit plasticity and functional recovery after stroke.
Specimen part
View SamplesSystemic vaccination with the attenuated virus SIVmac239-Nef provides sterilizing or partial protection to rhesus monkeys challenged with WT SIV strains, providing important opportunities to study key immunological components of a protective host response. Here we show that intravenous vaccination with SIVmac239-Nef provides two potentially crucial immunological barriers localized at mucosal surfaces that correlate with the vaccines protective effects against WT SIVmac251 vaginal challenge: 1) a conditioned and coordinated response from the mucosal epithelium that blunts the early inflammatory and chemotactic signalling cascade that aids virus propagation and expansion; 2) early on-site generation/diversification of SIV-specific Abs from ectopic germinal center-like lymphoid aggregates. This unique host response to WT SIVmac251 in the female reproductive tract of SIVmac239-Nef-vaccinated animals points to a multi-layered strategy for a protective host response during immunodeficiency virus exposurerapid induction of humroal immunity at mucosal surfaces without the deleterious inflammatory side effects tied to innate recognition of virus. This vaccine-induced host response highlights potential key protective mechanisms needed for an effective HIV vaccine
Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.
Sex, Specimen part
View SamplesInflorescence stages 1 to 12 from mutants involved in Arabidopsis small RNA metabolism. Three biological replicates of each mutant comprising at least 9 independent plants were harvested, and the expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the sample groups allow the identification of genes regulated by small RNAs (microRNAs and siRNAs).
microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
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