scholarly journals Mechanisms for the adverse effects of late gestational increases in maternal cortisol on the heart revealed by transcriptomic analyses of the fetal septum

2014 ◽  
Vol 46 (15) ◽  
pp. 547-559 ◽  
Author(s):  
Elaine M. Richards ◽  
Charles E. Wood ◽  
Maria Belen Rabaglino ◽  
Andrew Antolic ◽  
Maureen Keller-Wood
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Cell Apoptosis ◽  
Metabolic Pathways ◽  
Fetal Heart ◽  
Pathway Inference ◽  
Apoptosis Pathways ◽  
Altered Metabolism ◽  
Mitochondrial Number ◽  
Muscle Cell Apoptosis

We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol resulting from maternal infusion of cortisol (1 mg/kg/day) caused fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies we extended the cortisol infusion to term, finding a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol. To investigate effects of maternal cortisol on the heart, we performed transcriptomic analyses on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the transcriptomic effects of maternal cortisol infusion for 10 days (130 day cortisol vs 130 day control), or ∼25 days (140 day cortisol vs 140 day control) and of normal maturation (140 day control vs 130 day control) were performed. Gene ontology terms related to immune function and cytokine actions were significantly overrepresented as genes altered by both cortisol and maturation in the septa. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly overrepresented, consistent with our previous histologic findings. In the term fetuses (∼25 days of cortisol) nutrient pathways were significantly overrepresented, consistent with altered metabolism and reduced mitochondria. Analysis of mitochondrial number by mitochondrial DNA expression confirmed a significant decrease in mitochondria. The metabolic pathways modeled as altered by cortisol treatment to term were different from those modeled during maturation of the heart to term, and thus changes in gene expression in these metabolic pathways may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by stillbirth, including gestational diabetes, Cushing's disease and chronic stress.

scholarly journals Impact of Hydrogen on the Transcriptome of Sinorhizobium meliloti 1021 Using RNA-sequencing Technology

2020 ◽  
Vol 69 (1) ◽  
pp. 39-48
Author(s):  
RUIRUI LIU ◽  
LULU LI ◽  
ZHIYING LI ◽  
WEIWEI WANG
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Rna Sequencing ◽  
Metabolic Pathways ◽  
Sinorhizobium Meliloti ◽  
Hydrogen Treatment ◽  
Sequencing Technology ◽  
Pathway Analyses ◽  
The Relationship ◽  
Surrounding Soil

Hydrogen formed during nitrogen fixation in legumes can enter the surrounding soil and confer multiple benefits to crops. Here, we used Sinorhizobium meliloti 1021, whose genome was sequenced in 2001, as a model bacterium to study the relationship between the bacterium and legume. We investigated the effects of hydrogen on the gene expression in S. meliloti using RNA-sequencing technology. We identified 43 genes whose expression was altered by hydrogen treatment; among these, 39 were downregulated, and 4 were upregulated. These genes accounted for 1.5% of the total 2941 annotated genes of the S. meliloti genome. Gene ontology and pathway analyses revealed that the hydrogen-regulated genes were associated with catalytic activity and binding. Further, these genes were primarily involved in arginine, proline, and β-alanine metabolism. Real-time PCR revealed that the transcription levels of SMc02983, cyoB, cyoC, and cyoD were reduced after hydrogen treatment. These results provide a theoretical framework for exploring new metabolic pathways of S. meliloti.

scholarly journals OP0021 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN EARLY RHEUMATOID ARTHRITIS PATIENTS RESPONDING TO TOCILIZUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Gene Ontology ◽  
Regulatory T Cells ◽  
Early Rheumatoid Arthritis ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Double Blind

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared

scholarly journals Comparison of gene expression in the red imported fire ant (Solenopsis invicta) under different temperature conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Vatanparast ◽  
Robert T. Puckett ◽  
Deuk-Soo Choi ◽  
Youngjin Park
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
High Temperature ◽  
Temperature Stress ◽  
Solenopsis Invicta ◽  
Expression Profiles ◽  
Fire Ant ◽  
Molecular Response ◽  
Red Imported Fire Ant ◽  
Imported Fire Ant

AbstractThe red imported fire ant (RIFA), Solenopsis invicta Buren is native to South America and is known as a global problematic invasive species. This study focused on the molecular response of RIFA by comparing gene expression profiles after exposing ants to low (10 °C) and high (40 °C) temperature stress and comparing them to untreated controls (30 °C). A total of 99,085 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 19,154 were annotated with gene descriptions, gene ontology terms, and metabolic pathways. 86 gene ontology (GO) functional sub-groups and 23 EggNOG terms resulted. Differentially expressed genes (DEGs) with log2FC ≥ 10 were screened and were compared at different temperatures. We found 203, 48, and 66 specific DEGs co-regulated at 10, 20, and 40 °C. Comparing transcriptome profiles for differential gene expression resulted in various DE genes, including cytochrome P450, NADH dehydrogenase subunit 1, cuticle protein and heat shock protein (HSP), which have previously been reported to be involved in cold and high temperature resistance. GO analysis revealed that antioxidant activity is up-regulated under high temperature stress. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings provide a basis for future understanding of the adaptation mechanisms of RIFA and the molecular mechanisms underlying the response to low and high temperatures.

scholarly journals Marginal dietary zinc deficiency in vivo induces vascular smooth muscle cell apoptosis in large arteries

2013 ◽  
Vol 99 (3) ◽  
pp. 525-534 ◽  
Author(s):  
Keith Allen-Redpath ◽  
Ou Ou ◽  
John H. Beattie ◽  
In-Sook Kwun ◽  
Jorg Feldmann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Zinc Deficiency ◽  
Vascular Smooth Muscle Cell ◽  
Cell Apoptosis ◽  
Large Arteries ◽  
Muscle Cell Apoptosis

Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF-κB-mediated survival signaling☆

2006 ◽  
Vol 312 (8) ◽  
pp. 1289-1298 ◽  
Author(s):  
M LESKINEN ◽  
H HEIKKILA ◽  
M SPEER ◽  
J HAKALA ◽  
M LAINE ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cell Apoptosis ◽  
Survival Signaling ◽  
Muscle Cell Apoptosis ◽  
Mast Cell Chymase
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