scholarly journals Noise in Gene Expression: Origins, Consequences, and Control

Science ◽  
2005 ◽  
Vol 309 (5743) ◽  
pp. 2010-2013 ◽  
Author(s):  
J. M. Raser
Keyword(s):  
Gene Expression ◽  
Noise In Gene Expression ◽  
And Control

UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6

2020 ◽  
Vol 20 (12) ◽  
pp. 1487-1496 ◽  
Author(s):  
Midori Murakami ◽  
Hiroto Izumi ◽  
Tomoko Kurita ◽  
Chiho Koi ◽  
Yasuo Morimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Promoter Activity ◽  
Anticancer Agent ◽  
Cisplatin Resistance ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Target ◽  
Transcriptional Level ◽  
And Control ◽  
Resistant Cells

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

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.

scholarly journals Probing the effect of promoters on noise in gene expression using thousands of designed sequences

2014 ◽  
Vol 24 (10) ◽  
pp. 1698-1706 ◽  
Author(s):  
Eilon Sharon ◽  
David van Dijk ◽  
Yael Kalma ◽  
Leeat Keren ◽  
Ohad Manor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Noise In Gene Expression

Differentiation Associated Changes in Gene Expression Profiles of Interstitial Cystitis and Control Urothelial Cells

2008 ◽  
Vol 180 (6) ◽  
pp. 2681-2687 ◽  
Author(s):  
Deborah R. Erickson ◽  
Steven R. Schwarze ◽  
Justin K. Dixon ◽  
Curtis J. Clark ◽  
Matt A. Hersh
Keyword(s):  
Gene Expression ◽  
Interstitial Cystitis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Urothelial Cells ◽  
And Control

scholarly journals Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia

2022 ◽  
Vol 12 ◽  
Author(s):  
Beatrice E. Gee ◽  
Andrea Pearson ◽  
Iris Buchanan-Perry ◽  
Roger P. Simon ◽  
David R. Archer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Control Subjects ◽  
Non Coding Rna ◽  
And Control

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.

scholarly journals 808 Tertiary lymphoid structure gene signature detected in immune checkpoint inhibitor-associated renal immune related adverse event

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A845-A845
Author(s):  
Jamie Lin ◽  
Amanda Tchakarov ◽  
Noha Abdel-Wahab ◽  
Houssein Safa ◽  
Salah-Eddine Bentebibel ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Kidney Biopsy ◽  
Marker Gene ◽  
Prognostic Significance ◽  
Acute Interstitial Nephritis ◽  
Differentially Expressed ◽  
Cancer Center ◽  
Induced Response ◽  
And Control

BackgroundTertiary lymphoid structures (TLSs) have been previously associated with ICI induced response in patients with cancer, but a commensurate observation has not been made in ICI associated immune related adverse events (irAEs). Acute interstitial nephritis (AIN) is the predominant lesion reported in patients with renal irAEs, but various etiologies can also trigger the development of AIN including non-ICI drugs (e.g. non-steroidal anti-inflammatory drugs, antibiotics, proton pump inhibitors, etc.), and it is unknown whether these mechanisms are similar. With increasing indications for ICIs in cancer therapy, there is a critical need to define immune pathways driving the emergence of irAEs. To address this critical knowledge gap, we performed gene expression profiling on ICI-AIN, drug-AIN, and control (non-AIN) kidney biopsy specimens.MethodsTotal RNA extracted from ICI-AIN (n = 6), drug-AIN (n = 4), and control (n = 4) fixed formalin paraffin embedded archival kidney biopsy samples was analyzed by Nanostring nCounter PanCancer Immune Profiling Panel using NanoString nCounter FLEX Analysis System.ResultsThree comparisons were conducted: ICI-AIN vs control, drug-AIN vs control, and ICI-AIN vs drug-AIN. A total of 147 genes were differentially expressed in ICI-AIN vs control and the most differentially expressed genes were CXCL 9, 10, and 11. Similarly, cell marker gene expression signatures (GES) revealed significant upregulation of T and B cell markers in ICI-AIN vs control (P < 0.01) and ICI-AIN vs drug-AIN (T cell P < 0.05; B cell P < 0.01). Differences in T and B cell score were not detected in drug-AIN vs control. Since irAEs have been associated with anti-tumor efficacy, we investigated whether a TLS signature could be detected in ICI-AIN using a four GES (CD79A, MS4A1, LAMP3 and POU2AF1). The ICI-AIN group had significantly higher TLS score compared to both control and drug-AIN groups. Since several TLS signatures have been reported, we also calculated a 12-chemokine TLS GES which was also found to be statistically significant (P < 0.05). Th1 and Th17 cells have been associated with the formation of TLS, differential upregulation of Th1 associated genes but not Th17 associated genes were detected. Furthermore, differential expression IFN-y and TNF signature was also observed in ICI-AIN group.ConclusionsThis study is the first to demonstrate the presence of TLS immune signature in irAEs. Further investigations into the prognostic significance and strategies to uncouple ICI-associated anti-tumor benefits from ICI-induced irAEs should be explored.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition's Ethics Board, approval number PA16-1016

scholarly journals Chronic Gamma Irradiation Changes Phenotype and Gene Expression Partially Transmitted to Next-Generation Tomato Seedlings

Agronomy ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1638
Author(s):  
Seong-Min Kim ◽  
Yeong Deuk Jo ◽  
Jae-In Chun ◽  
Jin-Baek Kim ◽  
Jin-Ho Kang
Keyword(s):  
Gene Expression ◽  
Gamma Irradiation ◽  
Gamma Rays ◽  
Mutation Breeding ◽  
Fruit Shape ◽  
Leaf Length ◽  
Trichome Density ◽  
Next Generation ◽  
Seed Number ◽  
And Control

Compared to the studies on acute irradiation of seeds, fewer studies have reported on the chronic irradiation of seedlings, especially in fruit-bearing vegetables. We examined the effects of chronic gamma irradiation on tomato (Solanum lycopersicum ‘Micro-Tom’) seedlings exposed to gamma rays (50, 100, 150, and 200 Gy) for 4 weeks. As the total dose of gamma rays increased, leaf length, trichome density, and seed number were reduced in the irradiated seedlings (M1). Additionally, a change in fruit shape was observed. Chronic gamma irradiation reduced the expression of two trichome-related genes and affected the expression levels of 11 reactive oxygen species (ROS)-related genes. We examined the transmittance of these effects using M2 plants. The trichome density and fruit shape were similar between M2 and control plants; however, a reduction in leaf length and seed number was detected in M2 plants. Interestingly, changes in the expression of four ROS-related genes (ZAT10, Mn-SOD, POD3, and RBOH1) found in M1 were detected in M2 plants. Thus, the changes in phenotype and gene expression induced by chronic gamma irradiation were transmitted to the next generation. Additionally, we found novel mutants from M2 plants, suggesting that chronic gamma irradiation may be considered in tomato mutation breeding.

scholarly journals Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model

2021 ◽  
Vol 2 ◽  
Author(s):  
Selma Ben Hamouda ◽  
Maria Angélica Miglino ◽  
Gustavo de Sá Schiavo Matias ◽  
Guy Beauchamp ◽  
Jean-Pierre Lavoie
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Control Cell ◽  
3D Culture ◽  
Matrix Group ◽  
Cell Phenotype ◽  
Cell Control ◽  
Control Matrix ◽  
And Control

Asthma is associated with increased deposition and altered phenotype of airway smooth muscle (ASM) cells. However, little is known about the processes responsible for these changes. It has been suggested that alterations of the extracellular matrix (ECM) contribute to the remodeling of ASM cells in asthma. Three-dimensional matrices allow the in vitro study of complex cellular responses to different stimuli in a close-to-natural environment. Thus, we investigated the ultrastructural and genic variations of ASM cells cultured on acellular asthmatic and control bronchial matrices. We studied horses, as they spontaneously develop a human asthma-like condition (heaves) with similarities to chronic pulmonary changes observed in human asthma. Primary bronchial ASM cells from asthmatic (n = 3) and control (n = 3) horses were cultured on decellularized bronchi from control (n = 3) and asthmatic (n = 3) horses. Each cell lineage was used to recellularize six different bronchi for 41 days. Histomorphometry on HEPS-stained-recellularized matrices revealed an increased ASM cell number in the control cell/control matrix (p = 0.02) and asthmatic cell/control matrix group (p = 0.04) compared with the asthmatic cell/asthmatic matrix group. Scan electron microscopy revealed a cell invasion of the ECM. While ASM cells showed high adhesion and proliferation processes on the control ECM, the presence of senescent cells and cellular debris in the asthmatic ECM with control or asthmatic ASM cells suggested cell death. When comparing asthmatic with control cell/matrix combinations by targeted next generation sequencing, only AGC1 (p = 0.04), MYO10 (p = 0.009), JAM3 (p = 0.02), and TAGLN (p = 0.001) were differentially expressed out of a 70-gene pool previously associated with smooth muscle remodeling. To our knowledge, this is the first attempt to evaluate the effects of asthmatic ECM on an ASM cell phenotype using a biological bronchial matrix. Our results indicate that bronchial ECM health status contributes to ASM cell gene expression and, possibly, its survival.

scholarly journals Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Deling Zou ◽  
Yanyu Li ◽  
Guangping Sun
Keyword(s):  
Gene Expression ◽  
Renal Dysfunction ◽  
Treatment Options ◽  
Elevated Serum ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Current Treatment ◽  
Sprague Dawley ◽  
Kidney Injury Molecule 1 ◽  
And Control

Chronic heart failure (HF) frequently causes progressive decline in kidney function, known as cardiorenal syndrome-2 (CRS2). Current treatment options for CRS2 remain unacceptably limited. Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has recently been implicated in the pathogenesis of both HF and chronic kidney disease. Here we examined whether circulating TMAO is elevated in CRS2 and if so, whether attenuation of circulating TMAO would ameliorate the progression of CRS2. Sprague-Dawley rats underwent surgery for myocardial infarction (MI) or sham (week 0) followed by subtotal (5/6) nephrectomy (STNx) or sham at week 4 to induce CRS2 or control. At week 6, MI + STNx rats and control rats received vehicle or 1.0% 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) treatment for 8 weeks. Compared with control rats, MI + STNx rats exhibited elevated serum TMAO at week 6, which was increased further at week 14 but was attenuated by DMB treatment. MI + STNx rats showed cardiac dysfunction as assessed by echocardiography and renal dysfunction as evidenced by increased serum creatinine and urinary kidney injury molecule-1 and decreased creatinine clearance at week 6. The cardiac and renal dysfunction in MI + STNx rats was exacerbated at week 14 but was prevented by DMB treatment. Molecular and histological studies revealed myocyte hypertrophy and increases in interstitial myocardial fibrosis and gene expression of pro-hypertrophic and pro-fibrotic markers in both heart and kidney at week 14, which were accompanied by elevated gene expression of proinflammatory cytokines. The changes in molecular and histological parameters observed in MI + STNx rats were significantly reduced by DMB treatment. These findings suggest that rats with CRS2 have elevated circulating TMAO, which is associated with the exacerbation of cardiac and renal dysfunction. Attenuation of circulating TMAO can ameliorate cardiac and renal injury and prevents the progression of CRS2.

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