Microarray evaluation of bovine hepatic gene response to fescue toxicosis

2013 ◽  
Vol 6 (4) ◽  
pp. 419-426 ◽  
Author(s):  
D.D. Tanaree ◽  
J.M. Duringer ◽  
D.W. Bohnert ◽  
A.M. Craig
Keyword(s):  
Gene Expression ◽  
Cardiac Development ◽  
Cell Cycle Control ◽  
Average Daily Gain ◽  
Regulation Of Gene Expression ◽  
Clinical Signs ◽  
Ergot Alkaloids ◽  
Fungal Endophyte ◽  
Fescue Toxicosis ◽  
Cellular Mechanisms

‘Fescue toxicosis’ is a disease in livestock caused by ingestion of ergot alkaloids produced by the fungal endophyte Neotyphodium coenophialum in tall fescue; it is estimated to cost 1 billion USD in damages per year to the beef industry alone. Clinical signs include decreased reproductive fitness, necrosis of extremities, and reduced average daily gain and milk production. Little is known about the cellular mechanisms that mediate these toxic sequelae. We evaluated the effects of ergovaline-based fescue toxicosis on gene expression via oligonucleotide microarray. Liver biopsies were obtained from steers (n=4) pre- and post-exposure (0 and 29 days) to feed containing 579 ng/g ergovaline. Analyses were performed using both ANOVA with false discovery rate correction and Storey's optimal discovery procedure. Overall, down-regulation of gene expression was observed; heart contraction and cardiac development, apoptosis, cell cycle control, and RNA processing genes represented the bulk of differentially expressed transcripts. 2 CYPs (CYP2E1 and CYP4F6) were amongst the significantly upregulated results. Thus, exposure of cattle to toxic levels of ergovaline caused widespread changes in hepatic gene expression, which can both help explain macroscopic clinical signs observed in ruminant animals, and reinforce previous findings in monogastric models.

scholarly journals Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene.

1989 ◽  
Vol 9 (4) ◽  
pp. 1714-1720 ◽  
Author(s):  
J A Coppola ◽  
J M Parker ◽  
G D Schuler ◽  
M D Cole
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Constitutive Expression ◽  
Housekeeping Genes ◽  
Cell System ◽  
Myc Oncogene ◽  
Temporary Decrease ◽  
Mouse Erythroleukemia

Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.

scholarly journals Identification of a transcriptional signature found in multiple models of ASD and related disorders

2022 ◽  
Author(s):  
Samuel Thudium ◽  
Katherine C Palozola ◽  
Eloise L'Her ◽  
Erica Korb
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Neurodevelopmental Disorders ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Autism Spectrum ◽  
Cellular Mechanisms ◽  
Dynamic Regulation ◽  
Transcriptional Signature ◽  
Chromatin Modifiers

Epigenetic regulation plays a critical role in many neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). In particular, many such disorders are the result of mutations in genes that encode chromatin modifying proteins. However, while these disorders share many features, it is unclear whether they also share gene expression disruptions resulting from the aberrant regulation of chromatin. We examined 5 chromatin modifiers that are all linked to ASD despite their different roles in regulating chromatin. Specifically, we depleted Ash1L, Chd8, Crebbp, Ehmt1, and Nsd1 in parallel in a highly controlled neuronal culture system. We then identified sets of shared genes, or transcriptional signatures, that are differentially expressed following loss of multiple ASD-linked chromatin modifiers. We examined the functions of genes within the transcriptional signatures and found an enrichment in many neurotransmitter transport genes and activity-dependent genes. In addition, these genes are enriched for specific chromatin features such as bivalent domains that allow for highly dynamic regulation of gene expression. The downregulated transcriptional signature is also observed within multiple mouse models of neurodevelopmental disorders that result in ASD, but not those only associated with intellectual disability. Finally, the downregulated transcriptional signature can distinguish between neurons generated from iPSCs derived from healthy donors and idiopathic ASD patients through RNA-deconvolution, demonstrating that this gene set is relevant to the human disorder. This work identifies a transcriptional signature that is found within many neurodevelopmental syndromes, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in ASD.

scholarly journals Effects of folic acid supplementation to basal diets of broilers on growth performance, slaughter performance, IGF2 gene expression and methylation

2021 ◽  
Author(s):  
Xiuling Li ◽  
Yujie Zhang ◽  
Wenqian Jing ◽  
Weiqi Tang ◽  
Jinyi Xing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Folic Acid ◽  
Average Daily Gain ◽  
Regulation Of Gene Expression ◽  
Subcutaneous Fat ◽  
Water Soluble ◽  
Heart Weight ◽  
Control Group ◽  
Igf2 Gene ◽  
Positive Effects

Folic acid (FA) is an important water-soluble vitamin and plays an important role as a cofactor and coenzyme in animal growth and development, and regulation of gene expression and methylation. A total of 270 female broiler chickens (1-day-old) were randomly allotted to three dietary treatments supplemented with 0 mg/kg (control group), 5 mg/kg, and 10 mg/kg FA in basal diets for 42 days, respectively. Each treatment had six replicate cages with 15 birds per cage. Dietary supplementation of 5 mg/kg FA significantly enhanced average body weight and average daily gain of 21-day-old broilers (P < 0.05), but significantly reduced subcutaneous fat thickness and widths of an intermuscular fat band of 42-day-old broilers by dietary FA treatments (P < 0.05). Also, a diet with 10 mg/kg FA supplementation significantly increased the relative heart weight of 42-day-old chickens (P < 0.05). Furthermore, dietary FA supplementation significantly improved the serum insulin-like growth factor 2 (IGF2) concentrations (P < 0.01) and IGF2 mRNA expression in the abdominal fat (P < 0.05), but no statistical differences were found in the methylation of IGF2 promoter (P > 0.05). The present study demonstrated that dietary FA supplementation may have positive effects on chicken growth through increased IGF2 gene expression.  

scholarly journals Dysregulated micro-RNAs and long noncoding RNAs in cardiac development and pediatric heart failure

2020 ◽  
Vol 318 (5) ◽  
pp. H1308-H1315 ◽  
Author(s):  
Lee Toni ◽  
Frehiwet Hailu ◽  
Carmen C. Sucharov
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cardiovascular Development ◽  
Micro Rnas

Noncoding RNAs (ncRNAs) are broadly described as RNA molecules that are not translated into protein. The investigation of dysregulated ncRNAs in human diseases such as cancer, neurological, and cardiovascular diseases has been under way for well over a decade. Micro-RNAs and long noncoding RNAs (lncRNAs) are the best characterized ncRNAs. These ncRNAs can have profound effects on the regulation of gene expression during cardiac development and disease. Importantly, ncRNAs are significant regulators of gene expression in several congenital heart diseases and can positively or negatively impact cardiovascular development. In this review, we focus on literature involving micro-RNAs and lncRNAs in the context of pediatric cardiovascular diseases, preclinical models of heart failure, and cardiac development.

Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene

1989 ◽  
Vol 9 (4) ◽  
pp. 1714-1720
Author(s):  
J A Coppola ◽  
J M Parker ◽  
G D Schuler ◽  
M D Cole
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Constitutive Expression ◽  
Housekeeping Genes ◽  
Cell System ◽  
Myc Oncogene ◽  
Temporary Decrease ◽  
Mouse Erythroleukemia

Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.

scholarly journals miRNA degradation in the mammalian brain

2020 ◽  
Vol 319 (4) ◽  
pp. C624-C629
Author(s):  
Chun K. Kim ◽  
Toni R. Pak
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Mammalian Brain ◽  
Mirna Regulation ◽  
Cellular Mechanisms ◽  
Ongoing Research ◽  
Evolutionarily Conserved ◽  
Mirna Degradation ◽  
Neuronal Systems

MicroRNAs (miRNAs) are short, noncoding RNAs that are evolutionarily conserved across many different species. miRNA regulation of gene expression, specifically in the context of the mammalian brain, has been well characterized; however, the regulation of miRNA degradation is still a focus of ongoing research. This review focuses on recent findings concerning the cellular mechanisms that govern miRNA degradation, with an emphasis on target-mediated miRNA degradation and how this phenomenon is uniquely poised to maintain homeostasis in neuronal systems.

scholarly journals Impact of Ergot Alkaloids on Female Reproduction in Domestic Livestock Species

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 364 ◽  
Author(s):  
Rebecca K. Poole ◽  
Daniel H. Poole
Keyword(s):  
Hormone Secretion ◽  
Ergot Alkaloids ◽  
Economic Losses ◽  
Fescue Toxicosis ◽  
Female Reproduction ◽  
Negative Effects ◽  
Cellular Mechanisms ◽  
Livestock Species ◽  
Domestic Livestock ◽  
Grazing Livestock

Fescue toxicosis is a multifaceted syndrome that elicits many negative effects on livestock consuming ergot alkaloids produced by endophyte-infected tall fescue. The economic losses associated with fescue toxicosis are primarily due to reproductive failure including altered cyclicity, suppressed hormone secretion, reduced pregnancy rates, agalactia, and reduced offspring birth weights. For decades, a multitude of research has investigated the physiological and cellular mechanisms of these reproductive failures associated with fescue toxicosis. This review will summarize the various effects of ergot alkaloids on female reproduction in grazing livestock species.

Effects of Aminocyclopyrachlor Plus Metsulfuron on Tall Fescue Yield, Forage Quality, and Ergot Alkaloid Concentration

2016 ◽  
Vol 30 (1) ◽  
pp. 171-180 ◽  
Author(s):  
Trevor D. Israel ◽  
Gary E. Bates ◽  
Thomas C. Mueller ◽  
John C. Waller ◽  
G. Neil Rhodes
Keyword(s):  
Tall Fescue ◽  
Ergot Alkaloid ◽  
Crude Protein ◽  
Ergot Alkaloids ◽  
Forage Quality ◽  
The United States ◽  
Fungal Endophyte ◽  
Fescue Toxicosis ◽  
Protein Levels ◽  
Spring Harvest

Most tall fescue in the United States is infected with a fungal endophyte which imparts certain advantages to the plant, such as drought tolerance, insect feeding deterrence, and enhanced mineral uptake. However, the endophyte also produces ergot alkaloids that are harmful to livestock and contribute to fescue toxicosis. Because the alkaloids are concentrated in seed and stems, a potential way to reduce the likelihood of fescue toxicosis is by suppressing seedhead formation with herbicides. Research was conducted from 2012 to 2014 using metsulfuron applied alone and in combination with other herbicides in spring to determine the growth response of tall fescue, effects on forage quality, and ergot alkaloid concentration. Clipping or metsulfuron applied alone or in combination with aminocyclopyrachlor or aminopyralid reduced seedhead density by 36 to 55% compared to the nontreated control. Treatments containing metsulfuron reduced spring harvest yield 35 to 61%, but no differences were observed in the summer or year-after harvests. The same treatments increased crude protein levels by 1.03 to 2.14% and reduced acid detergent fiber levels by 1.60 to 2.76% compared to the nontreated control at spring harvest. Treatments containing metsulfuron reduced ergot alkaloid concentration 26 to 34% at the spring harvest, but no differences were observed in summer-harvested forage. Results from this study indicate metsulfuron applied alone or in combination with aminocyclopyrachlor or aminopyralid can potentially reduce the severity of fescue toxicosis and improve forage quality.

microRNAs in cardiac development and regeneration

2013 ◽  
Vol 125 (4) ◽  
pp. 151-166 ◽  
Author(s):  
Enzo R. Porrello
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Regulation Of Gene Expression ◽  
Cardiac Regeneration ◽  
Cardiac Differentiation ◽  
Evolutionarily Conserved ◽  
Post Transcriptional Regulation ◽  
Therapeutic Possibilities

Heart development involves the precise orchestration of gene expression during cardiac differentiation and morphogenesis by evolutionarily conserved regulatory networks. miRNAs (microRNAs) play important roles in the post-transcriptional regulation of gene expression, and recent studies have established critical functions for these tiny RNAs in almost every facet of cardiac development and disease. The realization that miRNAs are amenable to therapeutic manipulation has also generated considerable interest in the potential of miRNA-based drugs for the treatment of a number of human diseases, including cardiovascular disease. In the present review, I discuss well-established and emerging roles of miRNAs in cardiac development, their relevance to congenital heart disease and unresolved questions in the field for future investigation, as well as emerging therapeutic possibilities for cardiac regeneration.

scholarly journals microRNAs: fine tuning of erythropoiesis

2013 ◽  
Vol 18 (1) ◽  
Author(s):  
Marcin Listowski ◽  
Elżbieta Heger ◽  
Dżamila Bogusławska ◽  
Beata Machnicka ◽  
Kazimierz Kuliczkowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Quantitative Composition ◽  
Transcriptional Level ◽  
Cellular Mechanisms ◽  
Cell Proliferation And Differentiation ◽  
A Cell ◽  
Mirna Pathway

AbstractCell proliferation and differentiation is a complex process involving many cellular mechanisms. One of the best-studied phenomena in cell differentiation is erythrocyte development during hematopoiesis in vertebrates. In recent years, a new class of small, endogenous, non-coding RNAs called microRNAs (miRNAs) emerged as important regulators of gene expression at the post-transcriptional level. Thousands of miRNAs have been identified in various organisms, including protozoa, fungi, bacteria and viruses, proving that the regulatory miRNA pathway is conserved in evolution. There are many examples of miRNA-mediated regulation of gene expression in the processes of cell proliferation, differentiation and apoptosis, and in cancer genesis. Many of the collected data clearly show the dependence of the proteome of a cell on the qualitative and quantitative composition of endogenous miRNAs. Numerous specific miRNAs are present in the hematopoietic erythroid line. This review attempts to summarize the state of knowledge on the role of miRNAs in the regulation of different stages of erythropoiesis. Original experimental data and results obtained with bioinformatics tools were combined to elucidate the currently known regulatory network of miRNAs that guide the process of differentiation of red blood cells.

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