scholarly journals Effects of diethylcarbamazine and ivermectin treatment onBrugia malayigene expression in infected gerbils (Meriones unguiculatus)

2019 ◽  
Vol 5 ◽  
Author(s):  
Mary J. Maclean ◽  
W. Walter Lorenz ◽  
Michael T. Dzimianski ◽  
Christopher Anna ◽  
Andrew R. Moorhead ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Action ◽  
Meriones Unguiculatus ◽  
Current Control ◽  
Direct Result ◽  
Ivermectin Treatment ◽  
Treatment Groups ◽  
Parasite Survival ◽  
Insight Into

AbstractLymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug actionin vivo, we treated gerbils harbouring patentBrugia malayiinfections with 6 mg kg−1DEC, 0.15 mg kg−1ivermectin or 1 mg kg−1albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.

scholarly journals TOR signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Nicole Hawe ◽  
Konstantin Mestnikov ◽  
Riley Horvath ◽  
Mariam Eji-Lasisi ◽  
Cindy Lam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Nuclear Localization ◽  
Kinase Activity ◽  
Mediator Complex ◽  
Tor Signaling ◽  
A Subunit ◽  
Insight Into

AbstractCdk8 of the RNA Polymerase II mediator complex regulates genes by phosphorylating sequence specific transcription factors. Despite conserved importance for eukaryotic transcriptional regulation, the signals regulating Cdk8 are unknown. Full induction of the yeast GAL genes requires phosphorylation of Gal4 by Cdk8, and we exploited this requirement for growth of gal3 yeast on galactose to identify mutants affecting Cdk8 activity. Several mutants from the screen produced defects in TOR signaling. A mutant designated gal four throttle (gft) 1, gft1, was identified as an allele of hom3, encoding aspartokinase. Defects in gft1/ hom3 caused hypersensitivity to rapamycin, and constitutive nuclear localization of Gat1. Furthermore, mutations of tor1 or tco89, encoding TORC1 components, also prevented GAL expression in gal3 yeast, and tco89 was determined to be allelic to gft7. Disruption of cdc55, encoding a subunit of PP2A regulated by TOR signaling, suppressed the effect of gft1/ hom3, gft7/ tco89, and tor1 mutations on GAL expression in gal3 yeast, but not of cdk8/ srb10 disruptions or Gal4 S699A mutation. Mutations of gft1/ hom3 and tor1 did not affect kinase activity of Cdk8 in vitro, but caused loss of Gal4 phosphorylation in vivo. These observations demonstrate that TOR signaling regulates GAL induction through the activity of PP2A/ Cdc55, and are consistent with the contention that Cdk8-dependent phosphorylation of Gal4 S699 is opposed by PP2A/ Cdc55 dephosphorylation. These results provide insight into how induction of transcription by a specific inducer can be modulated by global nutritional signals through regulation of Cdk8-dependent phosphorylation.

scholarly journals A constitutively monomeric UVR8 photoreceptor allele confers enhanced UV-B photomorphogenesis

2020 ◽  
Author(s):  
Roman Podolec ◽  
Kelvin Lau ◽  
Timothée B. Wagnon ◽  
Michael Hothorn ◽  
Roman Ulm
Keyword(s):  
Gene Expression ◽  
Crystal Structure ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Genetic Tool ◽  
Loop Region ◽  
Extreme Uv ◽  
Insight Into

AbstractThe plant UV-B photoreceptor UVR8 plays an important role in UV-B acclimation and survival. UV-B absorption by homodimeric UVR8 induces its monomerization and interaction with the E3 ubiquitin ligase COP1, leading ultimately to gene expression changes. UVR8 is inactivated through redimerization, facilitated by RUP1 and RUP2. Here, we describe a novel semi-dominant, hyperactive allele, namely uvr8-17D, that harbors a glycine-101 to serine mutation. UVR8G101S-overexpression led to weak constitutive photomorphogenesis and extreme UV-B responsiveness. UVR8G101S was observed to be predominantly monomeric in vivo and, once activated by UV-B, was not efficiently inactivated. Analysis of a UVR8G101S crystal structure revealed the distortion of a loop region normally involved in stabilization of the UVR8 homodimer. Plants expressing a UVR8 variant combining G101S with the previously described W285A mutation exhibited robust constitutive photomorphogenesis. This work provides further insight into UVR8 activation and inactivation mechanisms, and describes a genetic tool for the manipulation of photomorphogenic responses.

scholarly journals TORC1 signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae

Genetics ◽  
2021 ◽  
Author(s):  
Riley Horvath ◽  
Nicole Hawe ◽  
Cindy Lam ◽  
Konstantin Mestnikov ◽  
Mariam Eji-Lasisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Nuclear Localization ◽  
Protein Phosphatase ◽  
Regulatory Subunit ◽  
Gal Genes ◽  
Dependent Site ◽  
Insight Into

Abstract Cdk8 of the RNA Polymerase II mediator kinase complex regulates gene expression by phosphorylating sequence-specific transcription factors. This function is conserved amongst eukaryotes, but the signals and mechanisms regulating Cdk8 activity and phosphorylation of its substrates are unknown. Full induction of the GAL genes in yeast requires phosphorylation of the transcriptional activator Gal4 by Cdk8. We used a screen to identify regulators of the Cdk8-dependent phosphorylation on Gal4, from which we identified multiple mutants with defects in TORC1 signaling. One mutant, designated gal four throttle 1 (gft1) was identified as a recessive allele of hom3, encoding aspartokinase, and mutations in hom3 caused effects typical of inhibition of TORC1, including rapamycin sensitivity and enhanced nuclear localization of the TORC1-responsive transcription factor Gat1. Mutations in hom3 also inhibit phosphorylation of Gal4 in vivo at the Cdk8-dependent site on Gal4, as did mutations of tor1, but these mutations did not affect activity of Cdk8 assayed in vitro. Disruption of cdc55, encoding a regulatory subunit of the TORC1-regulated protein phosphatase PP2A, suppressed the effect of hom3 and tor1 mutations on GAL expression, and also restored phosphorylation of Gal4 at the Cdk8-dependent site in vivo. These observations demonstrate that TORC1 signaling regulates GAL induction through the activity of PP2A/Cdc55, and suggest that Cdk8-dependent phosphorylation of Gal4 is opposed by PP2A/Cdc55 dephosphorylation. These results provide insight into how induction of transcription by a specific inducer can be modulated by global nutritional signals through regulation of Cdk8-dependent phosphorylation.

scholarly journals Gene Expression of PSORI-CM01 and Yinxieling in the Treatment of Psoriasis Vulgaris

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yue Lu ◽  
Yao Qi ◽  
Li Li ◽  
Yuhong Yan ◽  
Danni Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Group ◽  
Differentially Expressed Genes ◽  
Psoriasis Vulgaris ◽  
Drug Action ◽  
Differentially Expressed ◽  
Signalling Pathways ◽  
Control Group ◽  
Treatment Groups ◽  
Before And After

Background. This study aimed to explore the mechanisms of action of the PSORI-CM01 and Yinxieling formulas in the treatment of patients with psoriasis vulgaris by analyzing gene expression in peripheral blood mononuclear cells (PBMCs). Methods. PBMC samples were collected from 21 patients before and after treatment. The study included nine patients in the PSORI-CM01 treatment group, 12 patients in the Yinxieling treatment group, and nine patients in the healthy control group. Gene expression levels in PBMCs were determined using the Affymetrix gene chip technology. Results. In the PSORI-CM01 group before and after treatment, a total of 668 differentially expressed genes were found, of which 445 were upregulated and 223 were downregulated. Before and after Yinxieling treatment, 657 differentially expressed genes were found, of which 168 were upregulated and 489 were downregulated. Venn analysis showed that 78 genes were not differentially expressed in the PSORI-CM01 group and 74 were not differentially expressed in the Yinxieling group compared with those in the controls. Among these genes, 72 genes were common to both groups, which were the genes on which the two drugs acted jointly. The results of KEGG analysis and Venn analysis on the signalling pathways of drug action in treatment groups showed that haemostasis and pathways involving Rho GTPases were common signalling pathways of drug action in the two groups. Conclusions. By a comparative analysis of the treatment groups, we found that both drugs have a positive effect on patients with psoriasis vulgaris, primarily by regulating the pathways related to platelet activation, aggregation, and blood coagulation. Trial registration: ChiCTR, ChiCTR-TRC-14005185, Registered 8 August 2014, http://www.chictr.org.cn/showproj.aspx?proj=4390

scholarly journals Gene expression and thioguanine nucleotide disposition in acute lymphoblastic leukemia after in vivo mercaptopurine treatment

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1778-1785 ◽  
Author(s):  
Gianluigi Zaza ◽  
Meyling Cheok ◽  
Wenjian Yang ◽  
John C. Panetta ◽  
Ching-Hon Pui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Gene Probes ◽  
Thioguanine Nucleotide ◽  
Genomic Basis ◽  
Insight Into ◽  
In Vitro Data

Abstract To elucidate interpatient variability in thioguanine nucleotide (TGN) concentrations in acute lymphoblastic leukemia (ALL) cells, we determined the TGN concentrations in leukemic blasts from 82 children with newly diagnosed ALL after intravenous administration of mercaptopurine (MP). Patients treated with MP alone achieved higher TGN concentrations than those treated with the combination of methotrexate plus mercaptopurine (MTX + MP). Analysis of the expression of approximately 9600 genes in ALL cells obtained at diagnosis identified 60 gene probes significantly associated with TGN accumulation in patients treated with MP alone and 75 gene probes in patients treated with MTX + MP, with no overlap between the 2 sets of genes. Genes significantly associated with intracellular TGN accumulation after MP alone included those encoding MP metabolic enzymes and transporters (eg, SLC29A1). Inhibition of SLC29A1 by nitrobenzylmercaptopurine ribonucleoside (NBMPR) caused a 33% to 45% reduction of TGN in ALL cells in vitro (P < .006), consistent with the gene expression findings. Genes associated with TGN concentration after combination therapy included those involved in protein and adenosine triphosphate (ATP)-biosynthesis. Together, these in vivo and in vitro data provide new insight into the genomic basis of interpatient differences in intracellular TGN accumulation and reveal significant differences between treatment with MP alone and treatment with MP and MTX. (Blood. 2005;106:1778-1785)

scholarly journals Probing mechanisms of transcription elongation through cell-to-cell variability of RNA polymerase

2019 ◽  
Author(s):  
Md. Zulfikar Ali ◽  
Sandeep Choubey ◽  
Dipjyoti Das ◽  
Robert C. Brewster
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Regulation Of Gene Expression ◽  
Stochastic Simulations ◽  
Distribution Data ◽  
Recent Experimental Data ◽  
Gene Variability ◽  
Cell To Cell Variability ◽  
Insight Into

AbstractThe process of transcription initiation and elongation are primary points of control in the regulation of gene expression. While biochemical studies have uncovered the mechanisms involved in controlling transcription at each step, how these mechanisms manifestin vivoat the level of individual genes is still unclear. Recent experimental advances have enabled single-cell measurements of RNAP molecules engaged in the process of transcribing a gene of interest. In this manuscript, we use Gillespie simulations to show that measurements of cell-to-cell variability of RNAP numbers and inter-polymerase distances can reveal the prevailing mode of regulation of a given gene. Mechanisms of regulation at each step, from initiation to elongation dynamics, produce qualitatively distinct signatures which can further be used to discern between them. Intriguingly, depending on the initiation kinetics, stochastic elongation can either enhance or suppress cell-to-cell variability at the RNAP level. To demonstrate the value of this framework, we analyze RNAP number distribution data for ribosomal genes in S. cerevisiae from three previously published studies and show that this approach provides crucial mechanistic insights into the transcriptional regulation of these genes.Author SummaryThe process of transcription comprises many distinct steps and understanding the regulation of each of these steps provides insight into how the levels of gene expression are controlled in the cell. In this manuscript, we use stochastic simulations to explore how regulation at the level of elongation and initiation together influences the distribution of actively transcribing RNAP on a gene. We find that each of these steps of regulation leaves a distinct imprint on the gene-to-gene variability of number of actively transcribing RNAP on the gene and their inter-RNAP distances. Using these results, we analyze recent experimental data of transcribing RNAP distributions and find that the perturbations in these studies primarily impact the transcription initiation dynamics of the genes.

The characterization of PPARα ligand drug action in an in vivo model by comprehensive differential gene expression profiling

2001 ◽  
Vol 1 (5) ◽  
pp. 294-304 ◽  
Author(s):  
Bonnie E. Gould Rothberg ◽  
Scott S. Sundseth ◽  
Vincent A. DiPippo ◽  
Peter J. Brown ◽  
Deborah A. Winegar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Differential Gene Expression ◽  
Expression Profiling ◽  
Drug Action ◽  
In Vivo Model ◽  
Differential Gene

scholarly journals Ethanol Extract of Carica papaya Leaf Can Increase Breast Milk in Lactating Rat

2021 ◽  
Vol 9 (A) ◽  
pp. 520-526
Author(s):  
Yanti Herawati ◽  
Umi Kalsum ◽  
I Wayan Arsana Wiyasa ◽  
Lelly Yuniarti ◽  
Teguh Wahju Sardjono
Keyword(s):  
Gene Expression ◽  
Carica Papaya ◽  
Prolactin Receptor ◽  
Ethanol Extract ◽  
Control Group ◽  
Gene Expressions ◽  
Control Group Design ◽  
Treatment Groups ◽  
Post Test

BACKGROUND: Carica papaya leaves (Carica papaya L) have been used empirically and traditionally as a galactogogue, but their mechanism as galactogogue is still unknown. AIM: This study aimed to analyze the effect of ethanol extract from papaya leaves on blood prolactin levels, prolactin receptor (prlr) gene expression, the number of breast alveoli and lobes of lactating rats. METHODS: This in vivo true experimental study with a post-test control group design was conducted on 24 rats with the same lactating period. They were divided into four groups consisting of six rats each. The control group was given daily standard food, whereas the three treatment groups were, respectively, given additionally ethanol extract of 0.95 mg, 1.9 mg, and 3.8 mg/200 g BW/day from day 1 to day 14 of lactation. On day 14, all of the rats were sacrificed, blood prolactin levels were measured by ELISA, prlr gene expressions were measured using RT-PCR, and numbers of breast alveoli and lobes were microscopically observed through staining histological specimens. A statistical analysis was carried out using one-way ANOVA, Tukey's test, Games–Howell test, and path analysis at 95% confidence level. RESULTS: Levels of blood prolactin levels, prlr gene expression, the number of breast alveoli, and lobes of all treatment rat groups were significantly above those of the control group (p < 0.05). The increases of all parameters were consistent; the most effective dose was 1.9 mg/200 g BW. CONCLUSION: The Carica papaya leaf ethanol extract had a galactogogue effect on lactating rats by increasing blood prolactin levels, prlr gene expression, and numbers number of breast alveoli and lobes.

scholarly journals A constitutively monomeric UVR8 photoreceptor confers enhanced UV-B photomorphogenesis

2021 ◽  
Vol 118 (6) ◽  
pp. e2017284118
Author(s):  
Roman Podolec ◽  
Kelvin Lau ◽  
Timothée B. Wagnon ◽  
Michael Hothorn ◽  
Roman Ulm
Keyword(s):  
Gene Expression ◽  
Crystal Structure ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ultraviolet B ◽  
Genetic Tool ◽  
Loop Region ◽  
Extreme Uv ◽  
Insight Into

The plant ultraviolet-B (UV-B) photoreceptor UVR8 plays an important role in UV-B acclimation and survival. UV-B absorption by homodimeric UVR8 induces its monomerization and interaction with the E3 ubiquitin ligase COP1, leading ultimately to gene expression changes. UVR8 is inactivated through redimerization, facilitated by RUP1 and RUP2. Here, we describe a semidominant, hyperactive allele, namely uvr8-17D, that harbors a glycine-101 to serine mutation. UVR8G101S overexpression led to weak constitutive photomorphogenesis and extreme UV-B responsiveness. UVR8G101S was observed to be predominantly monomeric in vivo and, once activated by UV-B, was not efficiently inactivated. Analysis of a UVR8 crystal structure containing the G101S mutation revealed the distortion of a loop region normally involved in stabilization of the UVR8 homodimer. Plants expressing a UVR8 variant combining G101S with the previously described W285A mutation exhibited robust constitutive photomorphogenesis. This work provides further insight into UVR8 activation and inactivation mechanisms and describes a genetic tool for the manipulation of photomorphogenic responses.

scholarly journals Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chie Suzuki ◽  
Sarina Han ◽  
Gandhervin Kesavamoorthy ◽  
Mutsumi Kosugi ◽  
Kaori Araki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Marker ◽  
Marker Gene ◽  
Microglial Cells ◽  
Interleukin 4 ◽  
Expression Of Genes ◽  
Positron Emission ◽  
Insight Into

AbstractThe positron emission tomography probes 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes’ accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [14C]2DG and [18F]BCPP-EF to give a new insight into the hypothesis that different uptake of [18F]FDG and [18F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation. LPS or IL4 stimulation increased the proinflammatory or anti-inflammatory marker gene expression in microglial cells. In LPS-stimulated cells, [14C]2DG uptake and glycolysis related gene expression were elevated, and [18F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [18F]BCPP-EF uptake was increased, and [14C]2DG uptake was decreased. The expression of genes involved in glycolysis and mitochondrial complex I subunits was not changed by IL4 stimulation. The uptake of [14C]2DG and [18F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [18F]FDG and [18F]BCPP-EF can be influenced by the different aspects of neuroinflammation.

Sign in / Sign up

Export Citation Format

Share Document