scholarly journals Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 426 ◽  
Author(s):  
Liana V. Basova ◽  
James P. Kesby ◽  
Marcus Kaul ◽  
Svetlana Semenova ◽  
Maria Cecilia Garibaldi Marcondes
Keyword(s):  
Gene Expression ◽  
Systems Biology ◽  
Gene Transcription ◽  
Gene Networks ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Sirtuin 1 ◽  
The Brain ◽  
Hiv 1

Methamphetamine (Meth) abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein, trans-activator of transcription (Tat), has been described to induce changes in brain gene transcription that can result in impaired reward circuitry, as well as in inflammatory processes. In transgenic mice with doxycycline-induced Tat protein expression in the brain, i.e., a mouse model of neuroHIV, we tested global gene expression patterns induced by Meth sensitization. Meth-induced locomotor sensitization included repeated daily Meth or saline injections for seven days and Meth challenge after a seven-day abstinence period. Brain samples were collected 30 min after the Meth challenge. We investigated global gene expression changes in the caudate putamen, an area with relevance in behavior and HIV pathogenesis, and performed pathway and transcriptional factor usage predictions using systems biology strategies. We found that Tat expression alone had a very limited impact in gene transcription after the Meth challenge. In contrast, Meth-induced sensitization in the absence of Tat induced a global suppression of gene transcription. Interestingly, the interaction between Tat and Meth broadly prevented the Meth-induced global transcriptional suppression, by maintaining regulation pathways, and resulting in gene expression profiles that were more similar to the controls. Pathways associated with mitochondrial health, initiation of transcription and translation, as well as with epigenetic control, were heavily affected by Meth, and by its interaction with Tat in anti-directional ways. A series of systems strategies have predicted several components impacted by these interactions, including mitochondrial pathways, mTOR/RICTOR, AP-1 transcription factor, and eukaryotic initiation factors involved in transcription and translation. In spite of the antagonizing effects of Tat, a few genes identified in relevant gene networks remained downregulated, such as sirtuin 1, and the amyloid precursor protein (APP). In conclusion, Tat expression in the brain had a low acute transcriptional impact but strongly interacted with Meth sensitization, to modify effects in the global transcriptome.

Building Gene Networks by Analyzing Gene Expression Profiles

2019 ◽  
pp. 27-44
Author(s):  
Crescenzio Gallo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Gene Expressions ◽  
Over Time

The possible applications of modeling and simulation in the field of bioinformatics are very extensive, ranging from understanding basic metabolic paths to exploring genetic variability. Experimental results carried out with DNA microarrays allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. In this chapter, the authors examine various methods for analyzing gene expression data, addressing the important topics of (1) selecting the most differentially expressed genes, (2) grouping them by means of their relationships, and (3) classifying samples based on gene expressions.

Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns

2003 ◽  
Vol 90 (10) ◽  
pp. 688-697 ◽  
Author(s):  
Andrew Filer ◽  
Ewan Ross ◽  
Margarita Bofill ◽  
Stuart Martin ◽  
Mike Salmon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Human Fibroblasts ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Synovial Fibroblasts ◽  
Skin Fibroblasts ◽  
Inflammatory Reactions ◽  
Tnf Α

SummaryWe investigated the extent to which fibroblasts isolated from diverse tissues differ in their capacity to modulate inflammation by comparing the global gene expression profiles of cultured human fibroblasts from skin, acute and chronically inflamed synovium, lymph node and tonsil. The responses of these fibroblasts to TNF-α, IFN-γ and IL-4 stimulation were markedly different, as revealed by hierarchical cluster analysis and principal component analysis. In the absence of exogenous cytokine, syn-ovial and skin fibroblasts exhibited similar patterns of gene expression. However their transcriptional profiles diverged upon treatment with TNF-α.This proved to be biologically relevant, as TNF-α induced the secretion of different patterns and amounts of IL-6, IL-8 and CCL2 (MCP-1) in the two fibroblast types. Co-culture of skin or synovial fibroblasts with synovial fluid-derived mononuclear cells provided further evidence that these transcriptional differences were functionally significant in an ex vivo setting. Interestingly, the transcriptional response of skin fibroblasts to IL-4 converged with that of TNF-α-treated synovial fibroblasts, suggesting resident tissue fibroblasts and their blood-borne precursors may be imprinted by inflammatory cytokines that are characteristic of different tissues. Our data supports the concept that fibroblasts are heterogeneous, and that they contribute to the tissue-specificity of inflammatory reactions. Fibroblasts are therefore likely to play an active role in the persistence of chronic inflammatory reactions.This publication was partially financed by Serono Foundation for the Advancement of Medical Science.Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.

scholarly journals Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals

2004 ◽  
Vol 33 (3) ◽  
pp. 609-622 ◽  
Author(s):  
Knut R Steffensen ◽  
Soek Ying Neo ◽  
Thomas M Stulnig ◽  
Vinsensius B Vega ◽  
Safia S Rahman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Target Genes ◽  
Uncoupling Protein ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Liver X Receptors ◽  
Mouse Tissues ◽  
X Receptors

The liver X receptors α and β (LXRα and LXRβ ) are members of the nuclear receptor superfamily of proteins which are highly expressed in metabolically active tissues. They regulate gene expression of critical genes involved in cholesterol catabolism and transport, lipid and triglyceride biosynthesis and carbohydrate metabolism in response to distinct oxysterols and intermediates in the cholesterol metabolic pathway. The biological roles of the LXRs in tissues other than liver, intestine and adipose tissue are poorly elucidated. In this study we used global gene-expression profiling analysis to detect differences in expression patterns in several tissues from mice fed an LXR agonist or vehicle. Our results show that LXR plays an important role in the kidney, lung, adrenals, brain, testis and heart where several putative LXR target genes were found. The effects of the LXRs were further analysed in adrenals where treatment with an LXR agonist induced expression of adrenocorticotrophic hormone receptor, suppressed expression of uncoupling protein (UCP)-1 and UCP-3 as well as several glycolytic enzymes and led to increased serum corticosterone levels. These results indicate novel biological roles of the LXR including regulation of energy metabolism, glycolysis and steroidogenesis in the adrenals via alteration of expression profiles of putative target genes.

scholarly journals The Drosophila Gene Expression Tool (DGET) for expression analyses

2016 ◽  
Author(s):  
Yanhui Hu ◽  
Aram Comjean ◽  
Norbert Perrimon ◽  
Stephanie Mohr
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Data Retrieval ◽  
Design Stage ◽  
Expression Data ◽  
Similar Expression ◽  
Public Data

AbstractBackgroundNext-generation sequencing technologies have greatly increased our ability to identify gene expression levels, including at specific developmental stages and in specific tissues. Gene expression data can help researchers understand the diverse functions of genes and gene networks, as well as help in the design of specific and efficient functional studies, such as by helping researchers choose the most appropriate tissue for a study of a group of genes, or conversely, by limiting a long list of gene candidates to the subset that are normally expressed at a given stage or in a given tissue.ResultsWe report a Drosophila Gene Expression Tool (DGET, www.flyrnai.org/tools/dget/web/), which stores and facilitates search of RNA-Seq based expression profiles available from the modENCODE consortium and other public data sets. Using DGET, researchers are able to look up gene expression profiles, filter results based on threshold expression values, and compare expression data across different developmental stages, tissues and treatments. In addition, at DGET a researcher can analyze tissue or stage-specific enrichment for an inputted list of genes (e.g. ‘hits’ from a screen) and search for additional genes with similar expression patterns. We performed a number of analyses to demonstrate the quality and robustness of the resource. In particular, we show that evolutionary conserved genes expressed at high or moderate levels in both fly and human tend to be expressed in similar tissues. Using DGET, we compared whole tissue profile and sub-region/cell-type specific datasets and estimated the potential cause of false positives in one dataset. We also demonstrated the usefulness of DGET for synexpression studies by querying genes with similar expression profile to the mesodermal master regulator Twist.ConclusionAltogether, DGET provides a flexible tool for expression data retrieval and analysis with short or long lists of Drosophila genes, which can help scientists to design stage- or tissue-specific in vivo studies and do other subsequent analyses.

scholarly journals Gene Expression Patterns in Human Liver Cancers

2002 ◽  
Vol 13 (6) ◽  
pp. 1929-1939 ◽  
Author(s):  
Xin Chen ◽  
Siu Tim Cheung ◽  
Samuel So ◽  
Sheung Tat Fan ◽  
Christopher Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Gene Expression Patterns ◽  
Genotypic Differences ◽  
P53 Overexpression ◽  
Multiple Tumor ◽  
Liver Cancers ◽  
Genotypic Characteristics

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily distinguished from those associated with tumors metastatic to liver. The global gene expression patterns intrinsic to each tumor were sufficiently distinctive that multiple tumor nodules from the same patient could usually be recognized and distinguished from all the others in the large sample set on the basis of their gene expression patterns alone. The distinctive gene expression patterns are characteristic of the tumors and not the patient; the expression programs seen in clonally independent tumor nodules in the same patient were no more similar than those in tumors from different patients. Moreover, clonally related tumor masses that showed distinct expression profiles were also distinguished by genotypic differences. Some features of the gene expression patterns were associated with specific phenotypic and genotypic characteristics of the tumors, including growth rate, vascular invasion, and p53 overexpression.

Cryotolerance and global gene-expression patterns of Bos taurus indicus and Bos taurus taurus in vitro- and in vivo-produced blastocysts

2014 ◽  
Vol 26 (8) ◽  
pp. 1129 ◽  
Author(s):  
Mateus J. Sudano ◽  
Ester S. Caixeta ◽  
Daniela M. Paschoal ◽  
Alicio Martins ◽  
Rui Machado ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Bos Taurus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Embryo Viability ◽  
Bos Taurus Indicus

In a 2 × 2 factorial experimental design, embryo development, cryotolerance and global gene expression of Nellore (Bos taurus indicus) and Simmental (Bos taurus taurus) blastocysts produced in vitro (IVP) and in vivo (multiple ovulation derived embryo, MODE) were assessed. Blastocyst production was higher in Nellore than in Simmental (47.7 ± 2.0% vs 27.0 ± 2.0%) cows. The total numbers of ova or embryos recovered (5.5 ± 0.9 vs 3.7 ± 0.8) and transferable embryos (3.8 ± 1.0 vs 2.3 ± 0.8) per cow were not different between breeds. Simmental and MODE (34.6% and 38.5%, n = 75 and 70) blastocysts had higher survival rates after cryopreservation compared with Nellore and IVP (20.2% and 18.1%, n = 89 and 94) embryos, respectively. Differences between transcriptomes were addressed by principal-component analysis, which indicated that gene expression was affected by subspecies (158 genes), origin (532 genes) and interaction between both subspecies and origin (53 genes). Several functional processes and pathways relevant to lipid metabolism and embryo viability involving differentially expressed genes were identified. The lipid metabolism-related genes were upregulated in Simmental (AUH and ELOVL6) and IVP (ACSL3 and ACSL6) blastocysts. The expression profiles of genes related to mitochondrial metabolism (ATP5B), oxidative stress (GPX4), apoptosis (DAD1, DAP, PRDX2), heat shock (HSPA5), pregnancy (IFNT2, PAG2) and cell differentiation (KRT18) varied between experimental groups.

scholarly journals Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans

2017 ◽  
Author(s):  
Katharina Jovic ◽  
Mark G. Sterken ◽  
Jacopo Grilli ◽  
Roel P. J. Bevers ◽  
Miriam Rodriguez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Stress Response ◽  
Turning Point ◽  
Temporal Dynamics ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Small Time

AbstractThere is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.

Building Gene Networks by Analyzing Gene Expression Profiles

2018 ◽  
pp. 440-454
Author(s):  
Crescenzio Gallo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Gene Expressions ◽  
Over Time

The possible applications of modeling and simulation in the field of bioinformatics are very extensive, ranging from understanding basic metabolic paths to exploring genetic variability. Experimental results carried out with DNA microarrays allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. In this chapter we examine various methods for analyzing gene expression data, addressing the important topics of (1) selecting the most differentially expressed genes, (2) grouping them by means of their relationships, and (3) classifying samples based on gene expressions.

scholarly journals Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV+ Human Astrocytes: Implications for Shock or Lock Therapies in the Brain

2020 ◽  
Vol 94 (6) ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Anuja Ghorpade ◽  
Kathleen Borgmann
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Antiretroviral Drugs ◽  
Gene Expression Patterns ◽  
People Living With Hiv ◽  
Human Astrocytes ◽  
Living With Hiv ◽  
Hiv 1

ABSTRACT A significant number of people living with human immunodeficiency virus type 1 (HIV-1) suffer from HIV-associated neurocognitive disorders (HAND). Many previous studies investigating HIV in astrocytes as a heterogenous population have established the relevance of astrocytes to HIV-associated neuropathogenesis. However, these studies were unable to differentiate the state of infection, i.e., active or latent, or to evaluate how this affects astrocyte biology. In this study, the pseudotyped doubly labeled fluorescent reporter red/green (R/G)-HIV-1 was used to identify and enrich restricted and active populations of HIV+ astrocytes based on the viral promoter activity. Here, we report that the majority of human astrocytes restricted R/G-HIV-1 gene expression early during infection and were resistant to reactivation by vorinostat and interleukin 1β. However, actively infected astrocytes were inducible, leading to increased expression of viral proteins upon reactivation. R/G-HIV-1 infection also significantly decreased the cell proliferation and glutamate clearance ability of astrocytes, which may contribute to excitotoxicity. Moreover, transcriptome analyses to compare gene expression patterns of astrocyte harboring active versus restricted long terminal repeats (LTRs) revealed that the gene expression patterns were similar and that the active population demonstrated more widespread and robust changes. Our data suggest that harboring the HIV genome profoundly alters astrocyte biology and that strategies that keep the virus latent (e.g., block and lock) or those that reactivate the latent virus (e.g., shock and kill) would be detrimental to astrocyte function and possibly augment their contributions to HAND. IMPORTANCE More than 36 million people are living with HIV-1 worldwide, and despite antiretroviral therapy, 30 to 50% of the people living with HIV-1 suffer from mild to moderate neurocognitive disorders. HIV-1 reservoirs in the central nervous system (CNS) are challenging to address due to low penetration of antiretroviral drugs, lack of resident T cells, and permanent integration of provirus into neural cells such as microglia and astrocytes. Several studies have shown astrocyte dysfunction during HIV-1 infection. However, little is known about how HIV-1 latency affects their function. The significance of our research is in identifying that the majority of HIV+ astrocytes restrict HIV expression and were resistant to reactivation. Further, simply harboring the HIV genome profoundly altered astrocyte biology, resulting in a proinflammatory phenotype and functional changes. In this context, therapeutic strategies to reactivate or silence astrocyte HIV reservoirs, without excising proviral DNA, will likely lead to detrimental neuropathological outcomes during HIV CNS infection.

scholarly journals MUTYH is differentially expressed in glioblastoma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Brain Tissue ◽  
Microarray Data ◽  
Brain Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
The Poor ◽  
The Brain

Glioblastoma is the most common brain cancer in adults (1, 2). The poor prognostic outlook for patients diagnosed with glioblastoma demands an enhanced understanding of the basic transcriptional nature of glioblastoma tumors (1, 2). In this study we compared global gene expression profiles of glioblastoma tumors to that of the brain in health using published microarray data (3, 4). We found that mutY DNA glycosylase, or MUTYH was among the genes whose expression was most different between the transcriptomes of glioblastoma tumors and non-affected brain tissue. Mutations in MUTYH have been identified in pediatric gliomas (5) and this is the first report of perturbed differential expression of MUTYH in primary human glioblastoma tumors.

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