scholarly journals Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

2020 ◽  
Author(s):  
Anna Radlicka ◽  
Kinga Kamińska ◽  
Malgorzata Borczyk ◽  
Marcin Piechota ◽  
Michał Korostyński ◽  
...  
Keyword(s):  
Gene Expression ◽  
Frontal Cortex ◽  
Expression Patterns ◽  
Transcript Abundance ◽  
Motor Symptoms ◽  
Cellular Mechanisms ◽  
Drug Induced ◽  
Psychoactive Effects ◽  
Mixed Efficacy ◽  
6 Hydroxydopamine

AbstractThe development of Parkinson’s disease (PD) causes dysfunction of the frontal cortex, which contributes to hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-DOPA alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. In this study, we investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed an RNA-seq analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesion that were treated with L-3,4-dihydroxyphenylalanine (L-DOPA), for 2 weeks. We used analysis of variance to identify differentially expressed genes and found 48 genes with significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of 5 modules consisting of genes with similar expression patterns. The analyses led to three primary observations. First, the changes in gene expression induced by L-DOPA were bilateral, although only one hemisphere was lesioned. Second, the changes were not restricted to neurons but also appeared to emerge in immune or endothelial cells. Finally, comparisons with databases of drug-induced gene expression signatures revealed multiple nonspecific effects, which indicates that a part of the observed response is a common pattern activated by multiple types of pharmaceuticals in different target tissues. Taken together, our results identify cellular mechanisms in the frontal cortex that are involved in the response to L-DOPA treatment.

scholarly journals Patterns of thaumarchaeal gene expression in culture and diverse marine environments

2017 ◽  
Author(s):  
Paul Carini ◽  
Christopher L. Dupont ◽  
Alyson E. Santoro
Keyword(s):  
Gene Expression ◽  
Metabolic Regulation ◽  
Ammonia Oxidation ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Transcript Abundance ◽  
Ammonium Transporter ◽  
Growth State ◽  
Marine Habitats ◽  
Gene Coding

AbstractThaumarchaea are ubiquitous in marine habitats where they participate in carbon and nitrogen cycling. Although metatranscriptomes suggest thaumarchaea are active microbes in marine waters, we understand little about how thaumarchaeal gene expression patterns relate to substrate utilization and activity. Here, we report the global transcriptional response of the marine ammonia-oxidizing thaumarchaeon ‘CandidatusNitrosopelagicus brevis’ str. CN25 to ammonia limitation using RNA-Seq. We further describe the genome and transcriptome ofCa. N. brevis str. U25, a new strain capable of urea utilization. Ammonia limitation in CN25 resulted in reduced expression of transcripts coding for ammonia oxidation proteins, and increased expression of a gene coding an Hsp20-like chaperone. Despite significantly different transcript abundances across treatments, two ammonia monooxygenase subunits (amoAB), a nitrite reductase (nirK), and both ammonium transporter genes were always among the most abundant transcripts, regardless of growth state.Ca. N. brevis str. U25 cells expressed a urea transporter 139-fold more than the urease catalytic subunitureC. Gene co-expression networks derived from culture transcriptomes and ten thaumarchaea-enriched metatranscriptomes revealed a high degree of correlated gene expression across disparate environmental conditions and identified a module of genes, includingamoABCandnirK, that we hypothesize to represent the core ammonia oxidation machinery.Originality-Significance StatementDiscovering gene function in fastidious or uncultivated lineages remains one of the biggest challenges in environmental microbiology. Here, we use an approach that combines controlled laboratory experiments within situtranscript abundance data from the environment to identify genes that share similar transcription patterns in marine ammonia-oxidizing thaumarchaea. These findings demonstrate how transcriptomes from microbial cultures can be used together with complex environmental samples to identify suites of co-expressed genes that are otherwise enigmatic and provide new insights into the mechanism of ammonia oxidation. Our results add to the growing body of literature showing that relatively small changes in transcript abundance are linked to large changes in growth in organisms with reduced genomes, suggesting they have limited capacity for metabolic regulation or that they rely on mechanisms other than transcriptional regulation to deal with a fluctuating environment.

scholarly journals Changes in gene expression during drying and imbibition of desiccation sensitive Magnolia ovata (A. St.-Hil.) spreng. seeds

2009 ◽  
Vol 31 (1) ◽  
pp. 270-280 ◽  
Author(s):  
Anderson C. José ◽  
Wilco Ligterink ◽  
Antonio Claudio Davide ◽  
Edvaldo A. Amaral da Silva ◽  
Henk W.M. Hilhorst
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Initial Period ◽  
Expression Patterns ◽  
Transcript Abundance ◽  
Initial Water Content ◽  
Protective Mechanisms ◽  
Initial Water ◽  
Germination Behaviour ◽  
Water Contents

Seeds of Magnolia ovata were dried to different water contents to assess the viability and transcript abundance of genes related to seed development, cell cycle, cytoskeleton and desiccation tolerance.The expression of development, cell cycle and cytoskeleton relative genes (ABI3, CDC2-like and ACT2) alone could not explain the germination behaviour of M. ovata seeds in relation to drying damage. Irrespective of their initial water content, the seeds performed in the same way during the initial period of germination and the deleterious effects of desiccation only occurred in later stages. Expression of PKABA1, sHSP17.5 and 2-Cys-PRX did not show a relationship with desiccation. However, the expression patterns of PKABA1 and sHSP17.5 suggested the participation of these genes in protective mechanisms during the imbibition of M. ovata seeds.

scholarly journals Systems spatiotemporal dynamics of traumatic brain injury at single cell resolution reveals humanin as a therapeutic target

2021 ◽  
Author(s):  
Douglas Arneson ◽  
Guanglin Zhang ◽  
In Sook Ahn ◽  
Zhe Ying ◽  
Graciel Diamante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Frontal Cortex ◽  
Single Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Brain Regions ◽  
Cellular Heterogeneity ◽  
Blood Leukocytes

Abstract The etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains. We profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24hr) and chronic (7days) phases of mTBI at single cell resolution and demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling identified astrocytes as a key regulator of the cell-cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, and mt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes. Our results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.

scholarly journals Fine-tuned adaptation of embryo-endometrium pairs at implantation revealed by gene regulatory networks Tailored conceptus-maternal communication at implantation

2018 ◽  
Author(s):  
Fernando H. Biase ◽  
Isabelle Hue ◽  
Sarah E. Dickinson ◽  
Florence Jaffrezic ◽  
Denis Laloe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Strong Dependence ◽  
Expression Patterns ◽  
Transcript Abundance ◽  
Response Characteristic ◽  
Regulation Of Transcription ◽  
Functional Modules ◽  
Functional Analyses ◽  
Extraembryonic Tissues

ABSTRACTInteractions between embryo and endometrium at implantation are critical for the progression and the issue of pregnancy. These reciprocal actions involve exchange of paracrine signals that govern implantation and placentation. However, it remains unknown how these interactions between the conceptus and the endometrium are coordinated at the level of an individual pregnancy. Under the hypothesis that gene expression of endometrium is dependent on gene expression of extraembryonic tissues, we performed an integrative analysis of transcriptome profiles of paired conceptuses and endometria obtained from pregnancies initiated by artificial insemination. We quantified strong dependence (|r|>0.95, eFDR<0.01) in transcript abundance of genes expressed in the extraembryonic tissues and genes expressed in the endometrium. The profiles of connectivity revealed distinct co-expression patterns of extraembryonic tissues with caruncular and intercaruncular areas of the endometrium. Notably, a subset of highly co-expressed genes between conceptus (n=229) and caruncular areas of the endometrium (n=218, r>0.9999, eFDR<0.001) revealed a blueprint of gene expression specific to each pregnancy. Functional analyses of genes co-expressed between conceptus and endometrium revealed significantly enriched functional modules with critical contribution for implantation and placentation, including “in utero embryonic development”, “placenta development” and “regulation of transcription”. Functional modules were remarkably specific to caruncular or intercaruncular areas of the endometrium. The quantitative and functional association between genes expressed in conceptus and endometrium emphasize a coordinated communication between these two entities in mammals. To our knowledge, we provide first evidence that implantation in mammalian pregnancy relies on the ability of the conceptus and the endometrium to develop a fine-tuned adaptive response characteristic of each pregnancy.

scholarly journals Influence of Populus Genotype on Gene Expression by the Wood Decay Fungus Phanerochaete chrysosporium

2014 ◽  
Vol 80 (18) ◽  
pp. 5828-5835 ◽  
Author(s):  
Jill Gaskell ◽  
Amber Marty ◽  
Michael Mozuch ◽  
Philip J. Kersten ◽  
Sandra Splinter BonDurant ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phanerochaete Chrysosporium ◽  
Expression Patterns ◽  
Hybrid Poplar ◽  
Wood Decay ◽  
Transcript Abundance ◽  
Gene Expression Patterns ◽  
Parental Line ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass

ABSTRACTWe examined gene expression patterns in the lignin-degrading fungusPhanerochaete chrysosporiumwhen it colonizes hybrid poplar (Populus alba×tremula) and syringyl (S)-rich transgenic derivatives. A combination of microarrays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed detection of a total of 9,959 transcripts and 793 proteins. Comparisons ofP. chrysosporiumtranscript abundance in medium containing poplar or glucose as a sole carbon source showed 113 regulated genes, 11 of which were significantly higher (>2-fold,P< 0.05) in transgenic line 64 relative to the parental line. Possibly related to the very large amounts of syringyl (S) units in this transgenic tree (94 mol% S), several oxidoreductases were among the upregulated genes. Peptides corresponding to a total of 18 oxidoreductases were identified in medium consisting of biomass from line 64 or 82 (85 mol% S) but not in the parental clone (65 mol% S). These results demonstrate thatP. chrysosporiumgene expression patterns are substantially influenced by lignin composition.

scholarly journals Polymorphism and Divergence of Novel Gene Expression Patterns in Drosophila melanogaster

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 79-93
Author(s):  
Julie M. Cridland ◽  
Alex C. Majane ◽  
Hayley K. Sheehy ◽  
David J. Begun
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Transcript Abundance ◽  
Instar Larva ◽  
Accessory Gland ◽  
Male Reproduction ◽  
Specific Expression ◽  
Quantitative Expression ◽  
Female Head ◽  
Larval Salivary Gland

Transcriptomes may evolve by multiple mechanisms, including the evolution of novel genes, the evolution of transcript abundance, and the evolution of cell, tissue, or organ expression patterns. Here, we focus on the last of these mechanisms in an investigation of tissue and organ shifts in gene expression in Drosophila melanogaster. In contrast to most investigations of expression evolution, we seek to provide a framework for understanding the mechanisms of novel expression patterns on a short population genetic timescale. To do so, we generated population samples of D. melanogaster transcriptomes from five tissues: accessory gland, testis, larval salivary gland, female head, and first-instar larva. We combined these data with comparable data from two outgroups to characterize gains and losses of expression, both polymorphic and fixed, in D. melanogaster. We observed a large number of gain- or loss-of-expression phenotypes, most of which were polymorphic within D. melanogaster. Several polymorphic, novel expression phenotypes were strongly influenced by segregating cis-acting variants. In support of previous literature on the evolution of novelties functioning in male reproduction, we observed many more novel expression phenotypes in the testis and accessory gland than in other tissues. Additionally, genes showing novel expression phenotypes tend to exhibit greater tissue-specific expression. Finally, in addition to qualitatively novel expression phenotypes, we identified genes exhibiting major quantitative expression divergence in the D. melanogaster lineage.

177 EMBRYOS PRODUCED IN VITRO FROM PREPUBERTAL LAMB AND ADULT SHEEP OOCYTES DISPLAY DIFFERENT GENE EXPRESSION PATTERNS

2009 ◽  
Vol 21 (1) ◽  
pp. 187 ◽  
Author(s):  
D. Bebbere ◽  
L. Bogliolo ◽  
F. Ariu ◽  
S. Fois ◽  
G. Leoni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Production Systems ◽  
Expression Patterns ◽  
Heat Shock Protein 90 ◽  
Transcript Abundance ◽  
Blastocyst Stage ◽  
Developmental Competence ◽  
Adult Sheep

Breeding from prepubertal females reduces the generation interval and increases the rate of genetic gain in animal breeding programs. Despite considerable interest in this technology, its efficiency remains too low. Reduced in vitro and in vivo developmental competence of oocytes derived from prepubertal animals have been reported in association with morphologic, metabolic, and biochemical differences. The objective of this study was to compare the relative transcript abundance of a panel of developmentally important genes in embryos produced in vitro from prepubertal lamb and adult sheep oocytes. Cumulus–oocyte complexes derived from ovaries of regularly slaughtered 1-month-old prepubertal and adult sheep were matured in vitro in TCM-199 with 10% heat-treated oestrus sheep serum (OSS), 10 μL mL–1 of FSH/LH and 100 μm cysteamine, in 5% CO2 in air at 38.5°C for 24 h. Matured oocytes were fertilized with frozen–thawed ram semen in SOF medium + 2% OSS for 22 h at 38.5°C and 5% CO2, 5% O2, and 90% N2 atmosphere. Zygotes were cultured in SOF + AA + 0.4% BSA in 5% CO2 and 5% O2 up to blastocyst stage. Three groups of 10 blastocysts for each class (4 replicates) were used to quantify the relative expression of 15 genes by reverse transcription followed by real-time PCR. The relative quantification of the transcripts was performed with the 2-ddCt method (Livak and Schmittgen 2001 Methods 25, 402–408), after normalization against the β-actin expression levels. The analysis of gene expression evidenced higher relative abundance for Aquaporin 3, P34Cdc2, cyclin B, Oct4, H2A.Z, and Nanog transcripts in sheep embryos than in prepubertal-derived ones (ANOVA; P < 0.05), while interferon τ and insulin-like growth factor (IGF) 2 mRNAs were significantly more abundant in lamb-derived embryos (ANOVA; P < 0.01). No differences were observed for the remaining analyzed transcripts (BAX, IGF2R, heat shock protein 90, NaKATPase, E-cadherin, PAP, and glyceraldehyde 3-phosphate dehydrogenase). Overall, results show that embryos produced in vitro from prepubertal and adult oocytes display different patterns of expression at the blastocyst stage. Such difference may be related to the generally observed reduced in vitro and in vivo developmental competence. Increased understanding of the gene expression status during pre-implantation development may provide valuable insights into the molecular basis underlying the very early stages of life and an opportunity for optimizing in vitro embryo production systems.

Transcriptome and Translatome Regulation of Pathogenesis in Alzheimer’s Disease Model Mice

2022 ◽  
pp. 1-22
Author(s):  
Guillermo Eastman ◽  
Elizabeth R. Sharlow ◽  
John S. Lazo ◽  
George S. Bloom ◽  
José R. Sotelo-Silveira
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Ribosome Profiling ◽  
Mouse Strains ◽  
Translational Efficiency ◽  
Rna Seq ◽  
Cellular Mechanisms

Background: Defining cellular mechanisms that drive Alzheimer’s disease (AD) pathogenesis and progression will be aided by studies defining how gene expression patterns change during pre-symptomatic AD and ensuing periods of declining cognition. Previous studies have emphasized changes in transcriptome, but not translatome regulation, leaving the ultimate results of gene expression alterations relatively unexplored in the context of AD. Objective: To identify genes whose expression might be regulated at the transcriptome and translatome levels in AD, we analyzed gene expression in cerebral cortex of two AD model mouse strains, CVN (APPSwDI;NOS2 -/- ) and Tg2576 (APPSw), and their companion wild type (WT) strains at 6 months of age by tandem RNA-Seq and Ribo-Seq (ribosome profiling). Methods: Identical starting pools of bulk RNA were used for RNA-Seq and Ribo-Seq. Differential gene expression analysis was performed at the transcriptome, translatome, and translational efficiency levels. Regulated genes were functionally evaluated by gene ontology tools. Results: Compared to WT mice, AD model mice had similar levels of transcriptome regulation, but differences in translatome regulation. A microglial signature associated with early stages of Aβ accumulation was upregulated at both levels in CVN mice. Although the two mice strains did not share many regulated genes, they showed common regulated pathways related to AβPP metabolism associated with neurotoxicity and neuroprotection. Conclusion: This work represents the first genome-wide study of brain translatome regulation in animal models of AD and provides evidence of a tight and early translatome regulation of gene expression controlling the balance between neuroprotective and neurodegenerative processes in brain.

scholarly journals 3521 Distinct single cell gene expression in peripheral blood monocytes correlates with treatment response groups to TNF-alpha inhibition in rheumatoid arthritis

2019 ◽  
Vol 3 (s1) ◽  
pp. 8-9
Author(s):  
Theresa Wampler Muskardin ◽  
Zhongbo Jin ◽  
Jessica M. Dorschner ◽  
Yogita Ghodke-Puranik ◽  
Timothy Niewold
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Peripheral Blood ◽  
Target Genes ◽  
Biologic Therapy ◽  
Expression Patterns ◽  
Type I ◽  
Type I Ifn ◽  
Cellular Mechanisms ◽  
Α Activity

OBJECTIVES/SPECIFIC AIMS: The cellular mechanisms that underlie the IFNβ/α ratio that predicts response are not known. Effects of IFN on single immune cells may be masked in whole blood or mixed cell populations. By studying the effect of IFNβ/α activity ratio on individual monocytes, we can determine the functional impact of the IFN ratio and suggest the cellular mechanisms that underlie response/non-response to TNFi therapy in RA. METHODS/STUDY POPULATION: We used single cell analysis to investigate whether monocyte gene expression differs significantly between RA patients according to their pre-TNFi serum IFN-β/α ratio. Single classical (CL) and non-classical (NC) blood-derived monocytes were isolated from 15 seropositive RA subjects prior to biologic therapy. Subjects were grouped by pre-TNFi serum IFN-β/α ratio into two groups, those with a high IFN-β/α ratio (≥1.3, n = 6) and those with a low IFN-β/α ratio (<1.3, n = 9). 87 target genes were analyzed. Genes that varied significantly between the groups by categorical analyses were tested in multivariate logistic regression models. RESULTS/ANTICIPATED RESULTS: Every participant was seropositive for rheumatoid factor and antibodies to cyclic citrullinated peptide. Among the participants in the groups, there were no significant differences in age or DAS scores (P>0.05). The treatments were comparable and none were being treated with biologic therapy. There were striking differences in monocyte gene expression between patients with pre-treatment blood IFNβ/α activity <1.3 and ≥1.3. Expression of (1) key type I IFN pathway genes (JAK1, STAT2, IFIT2, IFIH1, PRDM1); (2) IL12; (3) CD36; and (4) CTLA4 were the strongest differentiators between groups (p<0.0001 for each, corrected for multiple comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: In this study we were able to measure gene expression in single monocytes from seropositive RA patients prior to biologic treatment. Within-cell co-expression patterns demonstrate biological differences in monocytes of RA patients with an IFNβ/α ≥1.3, the ratio of type I IFNs which predicts non-response to TNFi. The data suggest that there may be differential IFN production and pathway activation in patients who do not respond to TNFi. The increased expression of CD36 in monocytes from RA patients with high IFN β/α activity may be a reflection of increased “foam cells” in the inflamed tissue of patients who do not respond to TNFi. Enrichment of CTLA4 in those with high serum IFNβ/α suggests that CTLA4-Ig may be less likely to be an effective alternative for someone who is not likely to respond to TNFi. Current work includes determining whether the peripheral blood findings reflect altered cellular composition, type I IFN production and signaling in the synovium. Significance: This work will help to develop a more individualized approach to therapy in RA and determine an immunological basis of response/non-response to TNFi.

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