scholarly journals Changes in the gene expression profile during spontaneous migraine attacks

2020 ◽  
Author(s):  
Lisette J.A. Kogelman ◽  
Katrine Falkenberg ◽  
Alfonso Buil ◽  
Pau Erola ◽  
Julie Courraud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Migraine Attack ◽  
Molecular Mechanisms ◽  
Differential Expression Analysis ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Acid Oxidation ◽  
Rna Sequences ◽  
Subcutaneous Sumatriptan ◽  
Response To Stress

AbstractObjectiveMigraine occurs in clearly defined attacks and thus lends itself to investigate changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore is likely to reveal changes during a migraine attack. We examined the hypothesis that changes in RNA expression during and outside of a spontaneous migraine attack exist which are specific to the migraine attack.MethodsWe collected blood samples from 27 migraine patients during an attack, two hours after treatment with subcutaneous sumatriptan, on a headache-free day and after a cold pressor test. All patients were deeply phenotyped, including headache characteristics and treatment effect during the sampling. RNA-Sequencing, genotyping, and steroid profiling was performed on all samples. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and we integrated transcriptomic and genomic data.ResultsWe found 29 differentially expressed (DE) genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specific genes, i.e. genes related to a general pain/stress response. DE genes were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed molecular mechanisms affected by change in gene interactions during the migraine attack, e.g. ‘ion transmembrane transport’ and ‘response to stress’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’.InterpretationUsing a paired-sample design, we uniquely investigated intra-individual changes in the gene expression during a migraine attack. We revealed both genes and pathway potentially involved in the pathophysiology of migraine.

scholarly journals Changes in the gene expression profile during spontaneous migraine attacks

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisette J. A. Kogelman ◽  
Katrine Falkenberg ◽  
Alfonso Buil ◽  
Pau Erola ◽  
Julie Courraud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Migraine Attack ◽  
Differential Expression Analysis ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Acid Oxidation ◽  
Migraine Treatment ◽  
Rna Sequences ◽  
Transcriptomic Data ◽  
Gene Level

AbstractMigraine attacks are delimited, allowing investigation of changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore, we hypothesized that changes in RNA expression during and outside a spontaneous migraine attack exist which are specific to migraine. Twenty-seven migraine patients were assessed during a spontaneous migraine attack, including headache characteristics and treatment effect. Blood samples were taken during attack, two hours after treatment, on a headache-free day and after a cold pressor test. RNA-Sequencing, genotyping, and steroid profiling were performed. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and genomic and transcriptomic data were integrated. We found 29 differentially expressed genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specific genes, that were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed mechanisms affected by changes in gene interactions, e.g. ‘ion transmembrane transport’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’. In conclusion, we uniquely investigated intra-individual changes in gene expression during a migraine attack. We revealed both genes and pathways potentially involved in the pathophysiology of migraine and/or migraine treatment.

scholarly journals Sex differences in the human brain transcriptome of cases with schizophrenia

2020 ◽  
Author(s):  
Gabriel E. Hoffman ◽  
Yixuan Ma ◽  
Kelsey S. Montgomery ◽  
Jaroslav Bendl ◽  
Manoj Kumar Jaiswal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Differential Expression ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Age Of Onset ◽  
Differential Expression Analysis ◽  
Gene Expression Signature ◽  
Synaptic Organization ◽  
Expression Signature

AbstractWhile schizophrenia differs between males and females in age of onset, symptomatology and the course of the disease, the molecular mechanisms underlying these differences remain uncharacterized. In order to address questions about the sex-specific effects of schizophrenia, we performed a large-scale transcriptome analysis of RNA-seq data from 437 controls and 341 cases from two distinct cohorts from the CommonMind Consortium. Analysis across the cohorts identifies a reproducible gene expression signature of schizophrenia that is highly concordant with previous work. Differential expression across sex is reproducible across cohorts and identifies X- and Y-linked genes, as well as those involved in dosage compensation. Intriguingly, the sex expression signature is also enriched for genes involved in neurexin family protein binding and synaptic organization. Differential expression analysis testing a sex-by-diagnosis interaction effect did not identify any genome-wide signature after multiple testing corrections. Gene coexpression network analysis was performed to reduce dimensionality and elucidate interactions among genes. We found enrichment of co-expression modules for sex-by-diagnosis differential expression signatures, which were highly reproducible across the two cohorts and involve a number of diverse pathways, including neural nucleus development, neuron projection morphogenesis, and regulation of neural precursor cell proliferation. Overall, our results indicate that the effect size of sex differences in schizophrenia gene expression signatures is small and underscore the challenge of identifying robust sex-by-diagnosis signatures, which will require future analyses in larger cohorts.

scholarly journals A Computational Framework to Identify Transcriptional and Network Differences between Hepatocellular Carcinoma and Normal Liver Tissue and Their Applications in Repositioning Drugs

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Aimin Hu ◽  
Zheng Wei ◽  
Zuxiang Zheng ◽  
Bichao Luo ◽  
Jieming Yi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Differentially Expressed Genes ◽  
Expression Analysis ◽  
Molecular Mechanisms ◽  
Drug Repositioning ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Computational Framework ◽  
Normal Tissues

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Although there have been extensive studies on the molecular mechanisms of its carcinogenesis, FDA-approved drugs for HCC are rare. Side effects, development time, and cost of these drugs are the major bottlenecks, which can be partially overcome by drug repositioning. In this study, we developed a computational framework to study the mechanisms of HCC carcinogenesis, in which drug perturbation-induced gene expression signatures were utilized for repositioning of potential drugs. Specifically, we first performed differential expression analysis and coexpression network module analysis on the HCC dataset from The Cancer Genome Atlas database. Differential gene expression analysis identified 1,337 differentially expressed genes between HCC and adjacent normal tissues, which were significantly enriched in functions related to various pathways, including α-adrenergic receptor activity pathway and epinephrine binding pathway. Weighted gene correlation network analysis (WGCNA) suggested that the number of coexpression modules was higher in HCC tissues than in normal tissues. Finally, by correlating differentially expressed genes with drug perturbation-related signatures, we prioritized a few potential drugs, including nutlin and eribulin, for the treatment of hepatocellular carcinoma. The drugs have been reported by a few experimental studies to be effective in killing cancer cells.

Role of Fitness in Mediating Stress: A Correlational Exploration of Stress Reactivity

1991 ◽  
Vol 73 (3_suppl) ◽  
pp. 1171-1180 ◽  
Author(s):  
Jeffrey E. Brandon ◽  
J. Mark Loftin ◽  
Jack Curry
Keyword(s):  
Heart Rate ◽  
Physical Fitness ◽  
Stress Reactivity ◽  
Maximal Oxygen Consumption ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Self Report ◽  
Response To Stress ◽  
The Relationship

Researchers have investigated the effect of exercise on reducing subjects' responsiveness to stress. Results from the initial studies were positive, yet these studies often did not use objective measures of fitness. This investigation applied more rigorous methodology than past experiments to assess the relationship between fitness and reactivity to stress. Maximal oxygen consumption was measured to indicate the fitness of recreational cyclists who were then exposed to three stressful situations (mental subtraction, speech preparation, and the cold pressor test). Heart rate, frontalis electromyographic (EMG) levels, and self-report of tension were monitored during the stress-inducing tasks. Physical fitness was significantly related to heart rate taken during the subtraction and cold pressor tasks, with EMG during subtraction, and with self-report during all three stressor tasks. These results further support the hypothesized association of physical fitness and reducing response to stress.

scholarly journals Shared Molecular Mechanisms between Alzheimer’s Disease and Periodontitis Revealed by Transcriptomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Jieqi Jin ◽  
Mengkai Guang ◽  
Anthony Chukwunonso Ogbuehi ◽  
Simin Li ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Support Vector ◽  
Contributory Factor ◽  
Boruta Algorithm

Objective. To investigate the genetic crosstalk mechanisms that link periodontitis and Alzheimer’s disease (AD). Background. Periodontitis, a common oral infectious disease, is associated with Alzheimer’s disease (AD) and considered a putative contributory factor to its progression. However, a comprehensive investigation of potential shared genetic mechanisms between these diseases has not yet been reported. Methods. Gene expression datasets related to periodontitis were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed to identify differentially expressed genes (DEGs). Genes associated with AD were downloaded from the DisGeNET database. Overlapping genes among the DEGs in periodontitis and the AD-related genes were defined as crosstalk genes between periodontitis and AD. The Boruta algorithm was applied to perform feature selection from these crosstalk genes, and representative crosstalk genes were thus obtained. In addition, a support vector machine (SVM) model was constructed by using the scikit-learn algorithm in Python. Next, the crosstalk gene-TF network and crosstalk gene-DEP (differentially expressed pathway) network were each constructed. As a final step, shared genes among the crosstalk genes and periodontitis-related genes in DisGeNET were identified and denoted as the core crosstalk genes. Results. Four datasets (GSE23586, GSE16134, GSE10334, and GSE79705) pertaining to periodontitis were included in the analysis. A total of 48 representative crosstalk genes were identified by using the Boruta algorithm. Three TFs (FOS, MEF2C, and USF2) and several pathways (i.e., JAK-STAT, MAPK, NF-kappa B, and natural killer cell-mediated cytotoxicity) were identified as regulators of these crosstalk genes. Among these 48 crosstalk genes and the chronic periodontitis-related genes in DisGeNET, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 were shared and identified as the most pivotal candidate links between periodontitis and AD. Conclusions. Exploration of available transcriptomic datasets revealed C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 as the top candidate molecular linkage genes between periodontitis and AD.

scholarly journals A comprehensive catalogue of regulatory variants in the cattle transcriptome

2020 ◽  
Author(s):  
Shuli Liu ◽  
Yahui Gao ◽  
Oriol Canela-Xandri ◽  
Sheng Wang ◽  
Ying Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Economic Value ◽  
Tissue Expression ◽  
Genetic Associations ◽  
Rna Sequences ◽  
Regulatory Variants ◽  
Expression Atlas ◽  
Regulatory Effects

AbstractCharacterization of genetic regulatory variants acting on the transcriptome of livestock is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here, we build a cattle Genotype-Tissue Expression atlas (cGTEx, http://cgtex.roslin.ed.ac.uk/) for the research community based on 11,642 RNA sequences from publicly available datasets representing over 100 cattle tissues. We describe the landscape of the transcriptome across tissues and report hundreds of thousands of cis- and trans- genetic associations with gene expression and alternative splicing for 24 major tissues. We evaluate the specificity/similarity of these genetic regulatory effects across tissues, and functionally annotate them using a combination of multi-omics data. Finally, we link gene expression in different tissues to 43 economically important traits using a large transcriptome-wide association study (TWAS) to provide novel biological insights into the molecular regulatory mechanisms underpinning agronomic traits in cattle.

scholarly journals NutriGenomeDB: a nutrigenomics exploratory and analytical platform

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Roberto Martín-Hernández ◽  
Guillermo Reglero ◽  
José M Ordovás ◽  
Alberto Dávalos
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Molecular Mechanisms ◽  
Differential Expression Analysis ◽  
Gene Expression Omnibus ◽  
Human Cells ◽  
Bioactive Molecules ◽  
Protective Effects ◽  
Expression Data ◽  
Gene Sets

Abstract Habitual consumption of certain foods has shown beneficial and protective effects against multiple chronic diseases. However, it is not clear by which molecular mechanisms they may exert their beneficial effects. Multiple -omic experiments available in public databases have generated gene expression data following the treatment of human cells with different food nutrients and bioactive compounds. Exploration of such data in an integrative manner offers excellent possibilities for gaining insights into the molecular effects of food compounds and bioactive molecules at the cellular level. Here we present NutriGenomeDB, a web-based application that hosts manually curated gene sets defined from gene expression signatures, after differential expression analysis of nutrigenomics experiments performed on human cells available in the Gene Expression Omnibus (GEO) repository. Through its web interface, users can explore gene expression data with interactive visualizations. In addition, external gene signatures can be connected with nutrigenomics gene sets using a gene pattern-matching algorithm. We further demonstrate how the application can capture the primary molecular mechanisms of a drug used to treat hypertension and thus connect its mode of action with hosted food compounds.

scholarly journals Evaluation of Sympathetic Response in Offsprings of Hypertensive and Normotensive Parents

2020 ◽  
Vol 17 (4) ◽  
pp. 528-531
Author(s):  
Poonam Karmacharya ◽  
Surjit Singh ◽  
Indu Tiwari
Keyword(s):  
Cold Pressor Test ◽  
Cold Pressor ◽  
Sympathetic Response ◽  
Pressor Test ◽  
Hand Grip ◽  
History Of ◽  
Blood Pressures ◽  
Response To Stress ◽  
Family History Of Hypertension ◽  
Grip Test

Background: Disturbances of the autonomic nervous system play a crucial role in the pathogenesis and clinical course of many diseases. Sympathetic response is an exaggerated response to stress. Studies have shown that enhanced sympathetic response to stress is an indication of prehypertensive states. Young offspring of hypertensive parents are a good model for assessing sympathetic reactivity prior to clinical hypertension. The aim of this study is to compare the sympathetic response in normotensive offspring of both hypertensive and normotensive parents.Methods: 100 young normotensives, non-smoking and healthy students (male and female) of Manipal College of medical science with a family history of hypertension and 100 young normotensives students, non-smoking and healthy with a negative family history of hypertension were enrolled in the study. Blood pressures at rest and after Isometric hand grip test and cold pressor test were measured. Statistical analysis was done to compare the blood pressure at rest and after isometric hand grip exercise and cold pressor test using independent t test.Results: A statistically significant increase in systolic and diastolic blood pressures were observed in normotensive offspring of hypertensive parents, compared to the normotensive offspring of normotensive parents indicating sympathetic overactivity after isometric hand grip exercise and cold pressor test (P<0.001). Conclusions: Normotensive offspring of hypertensive parents showed increase sympathetic reactivity after stress was given in the form of isometric hand grip exercise and cold pressor test. Thus, normotensive offspring of hypertensive parents are more likely to develop future hypertension and the risk is greater when both the parents were hypertensive.Keywords: Cold pressor test; Isometric hand grip test; Sympathetic reactivity.

scholarly journals Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1529
Author(s):  
Nadezhda Bazhan ◽  
Tatiana Jakovleva ◽  
Natalia Feofanova ◽  
Elena Denisova ◽  
Anastasia Dubinina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Metabolic Response ◽  
Transcriptional Response ◽  
Acid Oxidation ◽  
Refeeding Syndrome ◽  
Transcriptional Responses ◽  
Hepatic Expression ◽  
Fasting And Refeeding ◽  
Sex Asymmetry

Fasting is often used for obesity correction but the “refeeding syndrome” limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.

scholarly journals The Importance of Adrenocortical Glucocorticoids for Adrenomedullary and Physiological Response to Stress: A Study in Isolated Glucocorticoid Deficiency

2001 ◽  
Vol 86 (12) ◽  
pp. 5920-5924 ◽  
Author(s):  
Nehama Zuckerman-Levin ◽  
Dov Tiosano ◽  
Graeme Eisenhofer ◽  
Stefan Bornstein ◽  
Ze’ev Hochberg
Keyword(s):  
Physiological Response ◽  
Acute Stress ◽  
Pressor Response ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Mild Stress ◽  
Compensatory Response ◽  
Response To Stress ◽  
Glucocorticoid Deficiency ◽  
Response To Exercise

Glucocorticoids are required for the normal functioning of chromaffin cells and their capacity to produce epinephrine. This was modeled in a unique clinical syndrome of isolated glucocorticoid deficiency due to unresponsiveness to ACTH. The working hypotheses were that in patients with isolated glucocorticoid deficiency, adrenomedullary epinephrine would be suppressed despite replacement therapy; that norepinephrine might show a compensatory response; and that the physiological response to stress would reflect these changes. Toward these hypotheses, patients with ACTH unresponsiveness on glucocorticoid replacement were subjected to three levels of acute stress: assumption of upright posture, cold pressor, and exercise. Their catecholamine and physiological response were monitored. Patients with isolated glucocorticoid deficiency of this study had severe adrenomedullary dysfunction, characterized by a minimal resting production of epinephrine (6 ± 2 pg/ml compared with 64 ± 22 pg/ml of the controls) and a minimal response to stress. A slight compensatory increase of norepinephrine was found in response to cold pressor test (754 ± 200 pg/ml compared with 431 ± 73 pg/ml of the control). The physiological response is characterized by low systolic blood pressure and high pulse rate in rest and mild stress and in a pressor response to exercise (diastolic 87 ± 5 mm Hg, compared with 73 ± 2 mm Hg of the control). It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response. The implications of the pressor response to exercise, the declining pulse pressure, and the increased pulse response insinuate a lower physical fitness in patients with adrenal insufficiency.

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