scholarly journals Expression of Interleukin 6 signaling receptors in carotid atherosclerosis

2020 ◽  
pp. 1358863X2097766
Author(s):  
Louise Ziegler ◽  
Jasmin Lundqvist ◽  
Kristian Dreij ◽  
Håkan Wallén ◽  
Ulf de Faire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Receptor Expression ◽  
Cerebrovascular Event ◽  
Expression Levels ◽  
Carotid Plaques ◽  
History Of ◽  
Cerebral Event ◽  
Signaling Receptors ◽  
Gene Expression Levels

Interleukin (IL) 6 contributes to atherosclerotic plaque development through IL6 membrane-bound (IL6R and gp130) and soluble (sIL6R and sgp130) receptors. We investigated IL6 receptor expression in carotid plaques and its correlation with circulating IL6 and soluble receptor levels. Plasma samples and carotid plaques were obtained from 78 patients in the Biobank of Karolinska Endarterectomies study. IL6, sIL6R, and sgp130 were measured in plasma and IL6, IL6R, sIL6R, GP130, and s GP130-RAPS (s GP130) gene expression assessed in carotid plaques. Correlations between plaque IL6 signaling gene expression and plasma levels were determined by Spearman’s correlation. Differences in plasma and gene expression levels between patients with ( n = 53) and without ( n = 25) a history of a cerebral event and statin-treated ( n = 65) and non-treated ( n = 11), were estimated by Kruskal–Wallis. IL6 and its receptors were all expressed in carotid plaques. There was a positive, borderline significant, moderate correlation between plasma IL6 and sIL6R and the respective gene expression levels (rho 0.23 and 0.22, both p = 0.05). IL6R expression was higher in patients with a history of a cerebrovascular event compared to those without ( p = 0.007). Statin-treated had higher IL6R, sIL6R, and s GP130 expression levels and plasma sIL6R compared to non-treated patients (all p < 0.05). In conclusion, all components of the IL6 signaling pathways are expressed in carotid artery plaques and IL6 and sIL6R plasma levels correlate moderately with IL6 and sIL6R. Our data suggest that IL6 signaling in the circulation might mirror the system activity in the plaque, thus adding novel perspectives to the role of IL6 signaling in atherosclerosis.

Somatostatin receptor subtypes 1-5 gene expression in multiple sites in the same individual.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 182-182
Author(s):  
Michael Anthony Hall ◽  
Tanja Milosavljevic ◽  
Peter Casey ◽  
Catherine T. Anthony ◽  
Eugene Woltering
Keyword(s):  
Gene Expression ◽  
Liver Metastasis ◽  
Primary Tumor ◽  
Normal Tissue ◽  
Somatostatin Receptor ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Expression Levels ◽  
Somatostatin Receptor Subtypes ◽  
Gene Expression Levels

182 Background: Metastatic tumors may be fundamentally different than the primary tumor. This phenomenon may partially explain resistance of metastatic disease to therapy. We evaluated the gene expression levels of somatostatin receptor subtypes 1-5 (SSTR 1-5) in patients with disseminated neuroendocrine tumors (NETS) undergoing cytoreduction of their primary tumor and its nodal and liver metastasis. Methods: We compared the gene expression levels for SSTR 1-5 in primary tumor and their nodal and liver metastasis. The small bowel primary (SB), a mesenteric lymph node (LN) and a liver metastasis and their normal tissue counterparts were evaluated in four patients. RNA samples from each tissue underwent gene expression analysis using a customized Real Time Quantitative PCR (RT-qPCR) gene array. Normal tissue gene expression was compared to that obtained from the tumor sample at each site. Results: SSTR 2 was overexpressed (four-fold or greater, p≤ 0.01) compared to control levels in 8/12 (67%) specimens; 4/4 (100%) of the liver specimens, 3/4 (75%) of the SB specimens, and 1/4 (25%) of the LN specimens. SSTR 2 gene overexpression was not observed in all three tumor sites in any patient. No tumor had SSTR 2 downregulation. SSTR 5 was overexpressed (four-fold or greater, p≤ 0.01) compared to control levels in 6/12 (50%) specimens; 3/4 (75%) of the liver specimens, 2/4 (50%) of the SB specimens, and 1/4 (25%) of the LN specimens. SSTR 5 gene expression was up-regulated in all three tumor sites in one individual. SSTR 5 was down-regulated (7-fold, p<0.01) in one LN specimen. Changes in gene expression levels of SSTR 3 and SSTR 4 showed inconsistency between tumor sites, whereas that of SSTR1 was observed only at the metastatic sites. Conclusions: These results explain the observed variability in somatostatin receptor expression seen in 111In pentetreotide scans in multiple tumor sites from the same individual. The observation that gene expression varies from metastasis to metastasis may also help explain the difficulty in designing therapies that cure patients rather than inducing partial remissions.

scholarly journals 3582 Scavenger Receptor Expression is Differentially Affected by DNAzyme-Gold Nanoparticle Conjugates

2019 ◽  
Vol 3 (s1) ◽  
pp. 20-21
Author(s):  
Cory Sylber ◽  
Jessica Petree ◽  
Nusaiba Baker ◽  
Khalid Salaita ◽  
Cherry Wongtrakool
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Therapeutic Potential ◽  
Scavenger Receptor ◽  
Surface Proteins ◽  
Receptor Expression ◽  
Scavenger Receptors ◽  
Expression Levels ◽  
Dose Dependent ◽  
Gene Expression Levels

OBJECTIVES/SPECIFIC AIMS: Scavenger receptor (SR) surface proteins are highly conserved motifs and are implicated in the uptake of nanotherapies. Gold nanoparticles functionalized with DNAzymes (DzNP) represent a promising novel nanotherapy for lung diseases such as asthma, particularly because they can be delivered directly to the lung. Our lab has been studying the therapeutic potential of a DzNP targeting GATA-3, a master transcription factor regulating Th2 inflammation. Although nanoparticle uptake through scavenger receptors has been described in macrophages in other models, the role of SRs in DzNP uptake in the lung is poorly understood. We hypothesize that scavenger receptors mediate DzNP uptake in alveolar macrophages. To begin examining this hypothesis, we examined whether DzNP exposure and uptake regulates gene expression of MARCO and MSR1, two class A scavenger receptors. METHODS/STUDY POPULATION: Using a silver stain, we measured dose dependent DzNP uptake in murine alveolar macrophages (MH-S). Using qRT-PCR, we measured gene expression of scavenger receptors MSR1 and MARCO in murine alveolar macrophages (MH-S) and after 24 hour exposure to 2251 DzNP, a DzNP targeting GATA-3, and dextran sulfate sodium (DSS), a known SR-A blocker. RESULTS/ANTICIPATED RESULTS: 2251 DzNP uptake in alveolar macrophages is dose dependent. MARCO gene expression levels significantly increase in murine alveolar macrophages when cultured with increasing concentrations of 2251 DzNP (10 pM-2 nM) or DSS 25-200 ug/ml) for 24 hours. However, MSR1 gene expression levels have minimal change when exposed to low concentrations of 2251 DzNP and DSS. At higher concentrations of 2251 DzNP and DSS, MSR1 expression levels are decreased. DISCUSSION/SIGNIFICANCE OF IMPACT: Alveolar macrophages exhibit a dose dependent increase in MARCO gene expression levels with increasing concentrations of 2251 DzNP and DSS, but MSR1 gene expression is not affected in a similar fashion. 2251 DzNP-induced increases in MARCO gene expression suggests that 2251 DzNP may facilitate its own uptake through MARCO. 2251 DzNP exposure negatively regulates MSR1 expression at higher doses and suggests that 2251 DzNP may inhibit its own uptake thought MSR1.

scholarly journals Local adaptation contributes to gene expression divergence in maize

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Jennifer Blanc ◽  
Karl A G Kremling ◽  
Edward Buckler ◽  
Emily B Josephs
Keyword(s):  
Gene Expression ◽  
Local Adaptation ◽  
Cold Response ◽  
Expression Levels ◽  
Maize Populations ◽  
Maize Genotypes ◽  
Wide Range ◽  
History Of ◽  
Insight Into ◽  
Gene Expression Levels

Abstract Gene expression links genotypes to phenotypes, so identifying genes whose expression is shaped by selection will be important for understanding the traits and processes underlying local adaptation. However, detecting local adaptation for gene expression will require distinguishing between divergence due to selection and divergence due to genetic drift. Here, we adapt a QST−FST framework to detect local adaptation for transcriptome-wide gene expression levels in a population of diverse maize genotypes. We compare the number and types of selected genes across a wide range of maize populations and tissues, as well as selection on cold-response genes, drought-response genes, and coexpression clusters. We identify a number of genes whose expression levels are consistent with local adaptation and show that genes involved in stress response show enrichment for selection. Due to its history of intense selective breeding and domestication, maize evolution has long been of interest to researchers, and our study provides insight into the genes and processes important for in local adaptation of maize.

Local adaptation contributes to gene expression divergence in maize

2020 ◽  
Author(s):  
Jennifer Blanc ◽  
Karl A. G. Kremling ◽  
Edward Buckler ◽  
Emily B. Josephs
Keyword(s):  
Gene Expression ◽  
Local Adaptation ◽  
Cold Response ◽  
Expression Levels ◽  
Maize Populations ◽  
Maize Genotypes ◽  
Wide Range ◽  
History Of ◽  
Insight Into ◽  
Gene Expression Levels

AbstractGene expression links genotypes to phenotypes, so identifying genes whose expression is shaped by selection will be important for understanding the traits and processes underlying local adaptation. However, detecting local adaptation for gene expression will require distinguishing between divergence due to selection and divergence due to genetic drift. Here, we adapt a QST –FST framework to detect local adaptation for transcriptome-wide gene expression levels in a population of diverse maize genotypes. We compare the number and types of selected genes across a wide range of maize populations and tissues, as well as selection on cold-response genes, drought-response genes, and coexpression clusters. We identify a number of genes whose expression levels are consistent with local adaptation and show that genes involved in stress-response show enrichment for selection. Due to its history of intense selective breeding and domestication, maize evolution has long been of interest to researchers, and our study provides insight into the genes and processes important for in local adaptation of maize.

scholarly journals A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Regression Model ◽  
The Cancer Genome Atlas ◽  
Low Rank ◽  
Expression Levels ◽  
Rank Regression ◽  
Prediction Of Prognosis ◽  
Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals Genome-Wide Expression and Alternative Splicing in Domesticated Sunflowers (Helianthus annuus L.) under Flooding Stress

Agronomy ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 92
Author(s):  
Joon Seon Lee ◽  
Lexuan Gao ◽  
Laura Melissa Guzman ◽  
Loren H. Rieseberg
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mixed Model ◽  
Agricultural Land ◽  
Alcohol Fermentation ◽  
Expression Levels ◽  
Flooding Stress ◽  
Genome Wide ◽  
And Control ◽  
Gene Expression Levels

Approximately 10% of agricultural land is subject to periodic flooding, which reduces the growth, survivorship, and yield of most crops, reinforcing the need to understand and enhance flooding resistance in our crops. Here, we generated RNA-Seq data from leaf and root tissue of domesticated sunflower to explore differences in gene expression and alternative splicing (AS) between a resistant and susceptible cultivar under both flooding and control conditions and at three time points. Using a combination of mixed model and gene co-expression analyses, we were able to separate general responses of sunflower to flooding stress from those that contribute to the greater tolerance of the resistant line. Both cultivars responded to flooding stress by upregulating expression levels of known submergence responsive genes, such as alcohol dehydrogenases, and slowing metabolism-related activities. Differential AS reinforced expression differences, with reduced AS frequencies typically observed for genes with upregulated expression. Significant differences were found between the genotypes, including earlier and stronger upregulation of the alcohol fermentation pathway and a more rapid return to pre-flooding gene expression levels in the resistant genotype. Our results show how changes in the timing of gene expression following both the induction of flooding and release from flooding stress contribute to increased flooding tolerance.

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