scholarly journals A Microarray Analysis of the Temporal Response of Liver to Methylprednisolone: A Comparative Analysis of Two Dosing Regimens

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2209-2225 ◽  
Author(s):  
Richard R. Almon ◽  
Debra C. DuBois ◽  
William J. Jusko
Keyword(s):  
Drug Infusion ◽  
Gene Chips ◽  
Product Function ◽  
Male Wistar Rats ◽  
Dosing Regimens ◽  
Single Bolus Dose ◽  
Temporal Profiles ◽  
Microarray Analyses ◽  
Gene Product Function ◽  
Glucocorticoid Action

Microarray analyses were performed on livers from adrenalectomized male Wistar rats chronically infused with methylprednisolone (MPL) (0.3 mg/kg·h) using Alzet mini-osmotic pumps for periods ranging from 6 h to 7 d. Four control and 40 drug-treated animals were killed at 10 different times during drug infusion. Total RNA preparations from the livers of these animals were hybridized to 44 individual Affymetrix REA230A gene chips, generating data for 15,967 different probe sets for each chip. A series of three filters were applied sequentially. These filters were designed to eliminate probe sets that were not expressed in the tissue, were not regulated by the drug, or did not meet defined quality control standards. These filters eliminated 13,978 probe sets (87.5%) leaving a remainder of 1989 probe sets for further consideration. We previously described a similar dataset obtained from animals after administration of a single dose of MPL (50 mg/kg given iv). That study involved 16 time points over a 72-h period. A similar filtering schema applied to the single-bolus-dose dataset identified 1519 probe sets as being regulated by MPL. A comparison of datasets from the two different dosing regimens identified 358 genes that were regulated by MPL in response to both dosing regimens. Regulated genes were grouped into 13 categories, mainly on gene product function. The temporal profiles of these common genes were subjected to detailed scrutiny. Examination of temporal profiles demonstrates that current perspectives on the mechanism of glucocorticoid action cannot entirely explain the temporal profiles of these regulated genes.

scholarly journals Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens

2007 ◽  
Vol 30 (3) ◽  
pp. 282-299 ◽  
Author(s):  
Richard R. Almon ◽  
Debra C. DuBois ◽  
Zhenling Yao ◽  
Eric P. Hoffman ◽  
Svetlana Ghimbovschi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Response ◽  
Data Sets ◽  
Gene Chips ◽  
Glucocorticoid Response ◽  
Constant Rate ◽  
Dosing Regimens ◽  
Chronic Corticosteroid ◽  
Temporal Profiles ◽  
Rate Infusion

The transcriptional response of skeletal muscle to chronic corticosteroid exposure was examined over 168 h and compared with the response profiles observed following a single dose of corticosteroid. Male adrenalectomized Wistar rats were given a constant-rate infusion of 0.3 mg·kg−1·h−1 methylprednisolone for up to 7 days via subcutaneously implanted minipumps. Four control and forty drug-treated animals were killed at ten different time points during infusion. Liver total RNAs were hybridized to 44 individual Affymetrix REA230A gene chips. Previously, we described a filtration approach for identifying genes of interest in microarray data sets developed from tissues of rats treated with methylprednisolone (MPL) following acute dosing. Here, a similar approach involving a series of three filters was applied sequentially to identify genes of interest. These filters were designed to eliminate probe sets that were not expressed in the tissue, not regulated by the drug, or did not meet defined quality control standards. Filtering eliminated 86% of probe sets, leaving a remainder of 2,316 for further consideration. In a previous study, 653 probe sets were identified as MPL regulated following administration of a single (acute) dose of the drug. Comparison of the two data sets yielded 196 genes identified as regulated by MPL in both dosing regimens. Because of receptor downregulation, it was predicted that genes regulated by receptor-glucocorticoid response element interactions would exhibit tolerance in chronic profiles. However, many genes did not exhibit steroid tolerance, indicating that present perspectives on the mechanism of glucocorticoid action cannot entirely explain all temporal profiles.

Test for temporal or spatial restrictions in gene product function during the cell division cycle

1983 ◽  
Vol 3 (7) ◽  
pp. 1255-1265
Author(s):  
S K Dutcher ◽  
L H Hartwell
Keyword(s):  
Cell Division ◽  
Gene Product ◽  
Gene Mutations ◽  
Cell Division Cycle ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Product Function ◽  
Complete Cell ◽  
Relationship Of ◽  
Gene Product Function

The ability of a functional gene to complement a nonfunctional gene may depend upon the intracellular relationship of the two genes. If so, the function of the gene product in question must be limited in time or in space. CDC (cell division cycle) gene products of Saccharomyces cerevisiae control discrete steps in cell division; therefore, they constitute reasonable candidates for genes that function with temporal or spatial restrictions. In an attempt to reveal such restrictions, we compared the ability of a CDC gene to complement a temperature-sensitive cdc gene in diploids where the genes are located within the same nucleus to complementation in heterokaryons where the genes are located in different nuclei. In CDC X cdc matings, complementation was monitored in rare heterokaryons by assaying the production of cdc haploid progeny (cytoductants) at the restrictive temperature. The production of cdc cytoductants indicates that the cdc nucleus was able to complete cell division at the restrictive temperature and implies that the CDC gene product was provided by the other nucleus or by cytoplasm in the heterokaryon. Cytoductants from cdc28 or cdc37 crosses were not efficiently produced, suggesting that these two genes are restricted spatially or temporally in their function. We found that of the cdc mutants tested 33 were complemented; cdc cytoductants were recovered at least as frequently as CDC cytoductants. A particularly interesting example was provided by the CDC4 gene. Mutations in CDC4 were found previously to produce a defect in both cell division and karyogamy. Surprisingly, the cell division defect of cdc4 nuclei is complemented by CDC4 nuclei in a heterokaryon, whereas the karyogamy defect is not.

scholarly journals Annotation of gene product function from high-throughput studies using the Gene Ontology

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Helen Attrill ◽  
Pascale Gaudet ◽  
Rachael P Huntley ◽  
Ruth C Lovering ◽  
Stacia R Engel ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Gene Product ◽  
High Throughput ◽  
Product Function ◽  
Gene Product Function

Rapamycin biosynthesis: elucidation of gene product function

2006 ◽  
Vol 4 (19) ◽  
pp. 3565 ◽  
Author(s):  
Matthew A. Gregory ◽  
Hui Hong ◽  
Rachel E. Lill ◽  
Sabine Gaisser ◽  
Hrvoje Petkovic ◽  
...  
Keyword(s):  
Gene Product ◽  
Product Function ◽  
Gene Product Function

scholarly journals Current achievements in modifying crop genes using CRISPR/Cas system

2019 ◽  
Vol 23 (1) ◽  
pp. 29-37 ◽  
Author(s):  
A. M. Korotkova ◽  
S. V. Gerasimova ◽  
E. K. Khlestkina
Keyword(s):  
Genome Editing ◽  
Crop Improvement ◽  
Plant Biotechnology ◽  
Research Papers ◽  
Product Function ◽  
One Year ◽  
Genome Modifications ◽  
Crop Genome ◽  
Huge Variety ◽  
Gene Product Function

With the advent of the new genome editing tool of target-specifically customizable endonucleases, a huge variety of novel opportunities have become feasible. The crop improvement is one of the main applications of genome editing in plant science and plant biotechnology. The amount of publications referring to genome editing and CRISPR/Cas system based molecular tools application in crops is permanently growing. The aim of this study is the systematization and cataloging of these data. Earlier we published the first catalog of targeted crop genome modifications as of February 10, 2017. The current review is an update of the catalog; it covers research papers on crop genome modifications from February 10, 2017 to August 17, 2018, found by searching 47 crop names in the Scopus database. Over one year and a half, 377 articles mentioning CRISPR/Cas and crop names have been published, of which 131 articles describe an experimental application of this tool for editing 193 genes in 19 crops, including rice with the largest number of genes modified (109 genes). Editing 50 of 193 genes was aimed at crop improvement. The catalog presented here includes these 50 genes, specifying the cultivars, each gene and gene product function, modification type and delivery method used. The current full list of genes modified with CRISPR/Cas with the aim of crop improvement is 81 in 16 crops (for 5 years from August 2013 to August 2018). In this paper, we also summarize data on different modifications types in different crops and provide a brief review of some novel methods and approaches that have appeared in crop genome editing research over the reviewed period. Taken together, these data provide a clear view on current progress in crop genome modifications and traits improvement using CRISPR/Cas based genome editing technology.

scholarly journals Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle

2005 ◽  
Vol 184 (1) ◽  
pp. 219-232 ◽  
Author(s):  
Richard R Almon ◽  
Debra C DuBois ◽  
Jin Y Jin ◽  
William J Jusko
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Expression Profiles ◽  
Peripheral Insulin Resistance ◽  
Methyl Prednisolone ◽  
Gene Chips ◽  
Enhanced Expression ◽  
Single Bolus Dose ◽  
Transcriptional Changes ◽  
Gene Transcripts

Elevated systemic levels of glucocorticoids are causally related to peripheral insulin resistance. The pharmacological use of synthetic glucocorticoids (corticosteroids) often results in insulin resistance/type II diabetes. Skeletal muscle is responsible for close to 80% of the insulin-induced systemic disposal of glucose and is a major target for glucocorticoid-induced insulin resistance. We used Affymetrix gene chips to profile the dynamic changes in mRNA expression in rat skeletal muscle in response to a single bolus dose of the synthetic glucocorticoid methyl-prednisolone. Temporal expression profiles (analyzed on individual chips) were obtained from tissues of 48 drug-treated animals encompassing 16 time points over 72 h following drug administration along with four vehicle-treated controls. Data mining identified 653 regulated probe sets out of 8799 present on the chip. Of these 653 probe sets we identified 29, which represented 22 gene transcripts, that were associated with the development of insulin resistance. These 29 probe sets were regulated in three fundamental temporal patterns. 16 probe sets coding for 12 different genes had a profile of enhanced expression. 10 probe sets coding for eight different genes showed decreased expression and three probe sets coding for two genes showed biphasic temporal signatures. These transcripts were grouped into four general functional categories: signal transduction, transcription regulation, carbohydrate/fat metabolism, and regulation of blood flow to the muscle. The results demonstrate the polygenic nature of transcriptional changes associated with insulin resistance that can provide a temporal scaffolding for translational and post-translational data as they become available.

ALLOANTISERUM INDUCED BLOCKADE OF IR GENE PRODUCT FUNCTION

1974 ◽  
pp. 175-190 ◽  
Author(s):  
W.E. Paul ◽  
E.M. Shevach ◽  
S.Z. Ben-Sasson ◽  
F. Finkelman ◽  
I. Green
Keyword(s):  
Gene Product ◽  
Product Function ◽  
Gene Product Function

scholarly journals Test for temporal or spatial restrictions in gene product function during the cell division cycle.

1983 ◽  
Vol 3 (7) ◽  
pp. 1255-1265 ◽  
Author(s):  
S K Dutcher ◽  
L H Hartwell
Keyword(s):  
Cell Division ◽  
Gene Product ◽  
Gene Mutations ◽  
Cell Division Cycle ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Product Function ◽  
Complete Cell ◽  
Relationship Of ◽  
Gene Product Function

The ability of a functional gene to complement a nonfunctional gene may depend upon the intracellular relationship of the two genes. If so, the function of the gene product in question must be limited in time or in space. CDC (cell division cycle) gene products of Saccharomyces cerevisiae control discrete steps in cell division; therefore, they constitute reasonable candidates for genes that function with temporal or spatial restrictions. In an attempt to reveal such restrictions, we compared the ability of a CDC gene to complement a temperature-sensitive cdc gene in diploids where the genes are located within the same nucleus to complementation in heterokaryons where the genes are located in different nuclei. In CDC X cdc matings, complementation was monitored in rare heterokaryons by assaying the production of cdc haploid progeny (cytoductants) at the restrictive temperature. The production of cdc cytoductants indicates that the cdc nucleus was able to complete cell division at the restrictive temperature and implies that the CDC gene product was provided by the other nucleus or by cytoplasm in the heterokaryon. Cytoductants from cdc28 or cdc37 crosses were not efficiently produced, suggesting that these two genes are restricted spatially or temporally in their function. We found that of the cdc mutants tested 33 were complemented; cdc cytoductants were recovered at least as frequently as CDC cytoductants. A particularly interesting example was provided by the CDC4 gene. Mutations in CDC4 were found previously to produce a defect in both cell division and karyogamy. Surprisingly, the cell division defect of cdc4 nuclei is complemented by CDC4 nuclei in a heterokaryon, whereas the karyogamy defect is not.

Levosimendan Does Not Improve Cardiac Output or Blood Pressure in a Rodent Model of Propranolol Toxicity When Administered Using Various Dosing Regimens

2012 ◽  
Vol 31 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Yasmean Kalam ◽  
Andis Graudins
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Rodent Model ◽  
Saline Control ◽  
Loading Dose ◽  
Treatment Groups ◽  
Male Wistar Rats ◽  
Dosing Regimens ◽  
Calcium Sensitizer ◽  
Propranolol Poisoning

Background: Levosimendan (CAS: 141505-33-1) is a myocardial calcium sensitizer that improves myocardial contractility in various forms of heart failure. It produces a moderate improvement in cardiac output (CO) without an improvement in blood pressure (BP) in verapamil and metoprolol poisoned rodents. Aim: To assess the effect of various levosimendan dosing regimens on hemodynamics in a rodent model of propranolol poisoning. Method: Male Wistar rats (350-450 g) were anesthetized, ventilated, and instrumented to record BP, heart rate (HR), and CO. Propranolol was infused continually. When BP dropped to 50% of baseline rats received 1 of 7 treatments: (1) 0.9% saline (control), (2) levosimendan 36 μg/kg loading dose then 0.6 μg/kg per min, (3) levosimendan 0.6 μg/kg per min, (4) epinephrine 0.5 μg/kg per min, (5) levosimendan 70 μg/kg loading dose then 1.2 μg/kg per min, (6) levosimendan 1.2 μg/kg per min, and (7) levosimendan 70 μg/kg loading dose alone. Hemodynamics were recorded every 10 minutes for 70 minutes. Cardiac output, mean arterial pressure, and HR for each group were compared with control. Results: All groups had comparable baseline and maximal toxicity hemodynamics prior to initiation of treatment. Levosimendan did not improve CO or BP with any dosing regimen. Blood pressure tended to be lower than control for all doses of levosimendan. Epinephrine significantly improved BP but not CO compared to all other treatment groups. Survival did not differ between groups. Conclusions: Unlike in verapamil and metoprolol poisoning models, levosimendan did not improve CO or survival in propranolol poisoning. Epinephrine improved BP, but not CO, suggesting that its actions were due to peripheral vasoconstriction.

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