scholarly journals Glucocorticoid-Mediated Developmental Programming of Vertebrate Stress Responsivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Ian M. Gans ◽  
James A. Coffman
Keyword(s):  
Regulatory Network ◽  
Allostatic Load ◽  
Target Gene ◽  
Acute Stress ◽  
Physiological Adaptation ◽  
Stress System ◽  
Metabolic Plasticity ◽  
Signaling Dynamics ◽  
Stress Responsivity ◽  
Feedback Regulator

Glucocorticoids, vertebrate steroid hormones produced by cells of the adrenal cortex or interrenal tissue, function dynamically to maintain homeostasis under constantly changing and occasionally stressful environmental conditions. They do so by binding and thereby activating nuclear receptor transcription factors, the Glucocorticoid and Mineralocorticoid Receptors (MR and GR, respectively). The GR, by virtue of its lower affinity for endogenous glucocorticoids (cortisol or corticosterone), is primarily responsible for transducing the dynamic signals conveyed by circadian and ultradian glucocorticoid oscillations as well as transient pulses produced in response to acute stress. These dynamics are important determinants of stress responsivity, and at the systemic level are produced by feedforward and feedback signaling along the hypothalamus-pituitary–adrenal/interrenal axis. Within receiving cells, GR signaling dynamics are controlled by the GR target gene and negative feedback regulator fkpb5. Chronic stress can alter signaling dynamics via imperfect physiological adaptation that changes systemic and/or cellular set points, resulting in chronically elevated cortisol levels and increased allostatic load, which undermines health and promotes development of disease. When this occurs during early development it can “program” the responsivity of the stress system, with persistent effects on allostatic load and disease susceptibility. An important question concerns the glucocorticoid-responsive gene regulatory network that contributes to such programming. Recent studies show that klf9, a ubiquitously expressed GR target gene that encodes a Krüppel-like transcription factor important for metabolic plasticity and neuronal differentiation, is a feedforward regulator of GR signaling impacting cellular glucocorticoid responsivity, suggesting that it may be a critical node in that regulatory network.

scholarly journals HSCVFNT: Inference of Time-Delayed Gene Regulatory Network Based on Complex-Valued Flexible Neural Tree Model

2018 ◽  
Vol 19 (10) ◽  
pp. 3178 ◽  
Author(s):  
Bin Yang ◽  
Yuehui Chen ◽  
Wei Zhang ◽  
Jiaguo Lv ◽  
Wenzheng Bao ◽  
...  
Keyword(s):  
Time Series ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Repair System ◽  
Tree Model ◽  
Scoring Method ◽  
Maximum Information ◽  
Gene Regulatory ◽  
Complex Valued

Gene regulatory network (GRN) inference can understand the growth and development of animals and plants, and reveal the mystery of biology. Many computational approaches have been proposed to infer GRN. However, these inference approaches have hardly met the need of modeling, and the reducing redundancy methods based on individual information theory method have bad universality and stability. To overcome the limitations and shortcomings, this thesis proposes a novel algorithm, named HSCVFNT, to infer gene regulatory network with time-delayed regulations by utilizing a hybrid scoring method and complex-valued flexible neural network (CVFNT). The regulations of each target gene can be obtained by iteratively performing HSCVFNT. For each target gene, the HSCVFNT algorithm utilizes a novel scoring method based on time-delayed mutual information (TDMI), time-delayed maximum information coefficient (TDMIC) and time-delayed correlation coefficient (TDCC), to reduce the redundancy of regulatory relationships and obtain the candidate regulatory factor set. Then, the TDCC method is utilized to create time-delayed gene expression time-series matrix. Finally, a complex-valued flexible neural tree model is proposed to infer the time-delayed regulations of each target gene with the time-delayed time-series matrix. Three real time-series expression datasets from (Save Our Soul) SOS DNA repair system in E. coli and Saccharomyces cerevisiae are utilized to evaluate the performance of the HSCVFNT algorithm. As a result, HSCVFNT obtains outstanding F-scores of 0.923, 0.8 and 0.625 for SOS network and (In vivo Reverse-Engineering and Modeling Assessment) IRMA network inference, respectively, which are 5.5%, 14.3% and 72.2% higher than the best performance of other state-of-the-art GRN inference methods and time-delayed methods.

Deciphering the transcription factor-microRNA-target gene regulatory network associated with graphene oxide cytotoxicity

2018 ◽  
Vol 12 (9) ◽  
pp. 1014-1026 ◽  
Author(s):  
Masoumeh Farahani ◽  
Mostafa Rezaei–Tavirani ◽  
Hakimeh Zali ◽  
Afsaneh Arefi Oskouie ◽  
Meisam Omidi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Graphene Oxide ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Microrna Target ◽  
Gene Regulatory

scholarly journals Innate antiviral defense demonstrates high energetic efficiency in a bony fish

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mark P. Polinski ◽  
Yangfan Zhang ◽  
Phillip R. Morrison ◽  
Gary D. Marty ◽  
Colin J. Brauner ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Allostatic Load ◽  
Sockeye Salmon ◽  
Acute Stress ◽  
Metabolic Cost ◽  
High Load ◽  
Energetic Efficiency ◽  
Antiviral Defense ◽  
Life Threatening ◽  
Interferon System

Abstract Background Viruses can impose energetic demands on organisms they infect, in part by hosts mounting resistance. Recognizing that oxygen uptake reliably indicates steady-state energy consumption in all vertebrates, we comprehensively evaluated oxygen uptake and select transcriptomic messaging in sockeye salmon challenged with either a virulent rhabdovirus (IHNV) or a low-virulent reovirus (PRV). We tested three hypotheses relating to the energetic costs of viral resistance and tolerance in this vertebrate system: (1) mounting resistance incurs a metabolic cost or limitation, (2) induction of the innate antiviral interferon system compromises homeostasis, and (3) antiviral defenses are weakened by acute stress. Results IHNV infections either produced mortality within 1–4 weeks or the survivors cleared infections within 1–9 weeks. Transcription of three interferon-stimulated genes (ISGs) was strongly correlated with IHNV load but not respiratory performance. Instead, early IHNV resistance was associated with a mean 19% (95% CI = 7–31%; p = 0.003) reduction in standard metabolic rate. The stress of exhaustive exercise did not increase IHNV transcript loads, but elevated host inflammatory transcriptional signaling up to sevenfold. For PRV, sockeye tolerated high-load systemic PRV blood infections. ISG transcription was transiently induced at peak PRV loads without associated morbidity, microscopic lesions, or major changes in aerobic or anaerobic respiratory performance, but some individuals with high-load blood infections experienced a transient, minor reduction in hemoglobin concentration and increased duration of excess post-exercise oxygen consumption. Conclusions Contrary to our first hypothesis, effective resistance against life-threatening rhabdovirus infections or tolerance to high-load reovirus infections incurred minimal metabolic costs to salmon. Even robust systemic activation of the interferon system did not levy an allostatic load sufficient to compromise host homeostasis or respiratory performance, rejecting our second hypothesis that this ancient innate vertebrate antiviral defense is itself energetically expensive. Lastly, an acute stress experienced during testing did not weaken host antiviral defenses sufficiently to promote viral replication; however, a possibility for disease intensification contingent upon underlying inflammation was indicated. These data cumulatively demonstrate that fundamental innate vertebrate defense strategies against potentially life-threatening viral exposure impose limited putative costs on concurrent aerobic or energetic demands of the organism.

Environments, Past and Present

2020 ◽  
Author(s):  
Angela Duckworth ◽  
Keyword(s):  
Allostatic Load ◽  
Acute Stress ◽  
The Body ◽  
Physiological Changes ◽  
Long Term Effects ◽  
Flight Response ◽  
Fight Or Flight Response ◽  
The Brain ◽  
Fight Or Flight

For more than a century, scientists have known that acute stress activates the fight-or-flight response. When your life is on the line, your body reacts instantly: your heart races, your breath quickens, and a cascade of hormones sets off physiological changes that collectively improve your odds of survival. More recently, scientists have come to understand that the fight-or-flight response takes a toll on the brain and the body—particularly when stress is chronic rather than acute. Systems designed to handle transient threats also react to stress that occurs again and again, for weeks, months, or years. It turns out that poverty, abuse, and other forms of adversity repeatedly activate the fight-or-flight response, leading to long-term effects on the immune system and brain, which in turn increase the risk for an array of illnesses, including asthma, diabetes, arthritis, depression, and cardiovascular disease. Pioneering neuroscientist Bruce McEwen called this burden of chronic stress “allostatic load.”

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

2020 ◽  
Author(s):  
Vijayakrishna Kolur ◽  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti ◽  
Anandkumar Tengli
Keyword(s):  
Coronary Artery Disease ◽  
Gene Ontology ◽  
Coronary Artery ◽  
Regulatory Network ◽  
Target Gene ◽  
Enrichment Analysis ◽  
Hub Genes ◽  
Go Enrichment ◽  
Artery Disease ◽  
Go Enrichment Analysis

Abstract BackgroundCoronary artery disease (CAD) is one of the most common disorders in the cardiovascular system. This study aims to explore potential signaling pathways and important biomarkers that drive CAD development. MethodsThe CAD GEO Dataset GSE113079 was featured to screen differentially expressed genes (DEGs). The pathway and Gene Ontology (GO) enrichment analysis of DEGs were analyzed using the ToppGene. We screened hub and target genes from protein-protein interaction (PPI) networks, target gene - miRNA regulatory network and target gene - TF regulatory network, and Cytoscape software. Validations of hub genes were performed to evaluate their potential prognostic and diagnostic value for CAD. Results1,036 DEGs were captured according to screening criteria (525upregulated genes and 511downregulated genes). Pathway and Gene Ontology (GO) enrichment analysis of DEGs revealed that these up and down regulated genes are mainly enriched in thyronamine and iodothyronamine metabolism, cytokine-cytokine receptor interaction, nervous system process, cell cycle and nuclear membrane. Hub genes were validated to find out potential prognostic biomarkers, diagnostic biomarkers and novel therapeutic target for CAD. ConclusionsIn summary, our findings discovered pivotal gene expression signatures and signaling pathways in the progression of CAD. CAPN13, ACTBL2, ERBB3, GATA4, GNB4, NOTCH2, EXOSC10, RNF2, PSMA1 and PRKAA1 might contribute to the progression of CAD, which could have potential as biomarkers or therapeutic targets for CAD.

scholarly journals La teoría de la alóstasis como mecanismo explicativo entre los apegos inseguros y la vulnerabilidad a enfermedades crónicas

2015 ◽  
Vol 31 (2) ◽  
pp. 452
Author(s):  
Mariantonia Lemos
Keyword(s):  
Allostatic Load ◽  
Stressful Life Events ◽  
The Body ◽  
Stressful Events ◽  
Stress System ◽  
Early Age ◽  
Secure Attachment ◽  
Stress Regulation ◽  
Physiological Processes ◽  
The Impact

The attachment bond has been proven to be a vulnerability factor for chronic diseases. This article seeks to clarify this relationship by the theory of allostasis. Allostasis theory refers to the regulation of complex physiological processes by systemic response in the body maintaining physiological stability when a person is confronted by challenges. The insecure attachments confront children from his first years with stressful events, by failing to provide security, fundamental purpose of attachment. In this way insecure attachments could impact the calibration of the stress system in the early age and would be factors that increases the allostatic load by a larger number of stressful life events compare to people with secure attachment, a cognitive appraisal of threat that leads to the development of hypervigilance and the impact on stress regulation systems in the body.

scholarly journals Mining Featured Biomarkers Linked with Epithelial Ovarian Cancer Based on Bioinformatics

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 39
Author(s):  
◽  
Chanabasayya Vastrad ◽  
◽  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Enrichment Analysis ◽  
Microrna Target ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Go Enrichment ◽  
Gene Regulatory ◽  
Go Enrichment Analysis

: Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information for further research. The gene expression profiles of E-MTAB-3706 which contained four high-grade ovarian epithelial cancer samples, four normal fallopian tube samples and four normal ovarian epithelium samples were downloaded from the ArrayExpress database. Pathway enrichment and Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) were performed, and protein-protein interaction (PPI) network, microRNA-target gene regulatory network and TFs (transcription factors ) -target gene regulatory network for up- and down-regulated were analyzed using Cytoscape. In total, 552 DEGs were found, including 276 up-regulated and 276 down-regulated DEGs. Pathway enrichment analysis demonstrated that most DEGs were significantly enriched in chemical carcinogenesis, urea cycle, cell adhesion molecules and creatine biosynthesis. GO enrichment analysis showed that most DEGs were significantly enriched in translation, nucleosome, extracellular matrix organization and extracellular matrix. From protein-protein interaction network (PPI) analysis, modules, microRNA-target gene regulatory network and TFs-target gene regulatory network for up- and down-regulated, and the top hub genes such as E2F4, SRPK2, A2M, CDH1, MAP1LC3A, UCHL1, HLA-C (major histocompatibility complex, class I, C) , VAT1, ECM1 and SNRPN (small nuclear ribonucleoprotein polypeptide N) were associated in pathogenesis of EOC. The high expression levels of the hub genes such as CEBPD (CCAAT enhancer binding protein delta) and MID2 in stages 3 and 4 were validated in the TCGA (The Cancer Genome Atlas) database. CEBPD andMID2 were associated with the worst overall survival rates in EOC. In conclusion, the current study diagnosed DEGs between normal and EOC samples, which could improve our understanding of the molecular mechanisms in the progression of EOC. These new key biomarkers might be used as therapeutic targets for EOC.

scholarly journals Social Allostasis and Social Allostatic Load: A New Model for Research in Social Dynamics, Stress, and Health

2019 ◽  
Vol 15 (2) ◽  
pp. 469-482 ◽  
Author(s):  
Darby E. Saxbe ◽  
Lane Beckes ◽  
Sarah A. Stoycos ◽  
James A. Coan
Keyword(s):  
Allostatic Load ◽  
Social Dynamics ◽  
Social Groups ◽  
Regulatory Function ◽  
Stress System ◽  
Regulatory Processes ◽  
Regulatory Systems ◽  
Wear And Tear ◽  
Highly Correlated ◽  
Stress And Health

Theories such as social baseline theory have argued that social groups serve a regulatory function but have not explored whether this regulatory process carries costs for the group. Allostatic load, the wear and tear on regulatory systems caused by chronic or frequent stress, is marked by diminished stress system flexibility and compromised recovery. We argue that allostatic load may develop within social groups as well and provide a model for how relationship dysfunction operates. Social allostatic load may be characterized by processes such as groups becoming locked into static patterns of interaction and may ultimately lead to up-regulation or down-regulation of a group’s set point, or the optimal range of arousal or affect around which the group tends to converge. Many studies of emotional and physiological linkage within groups have reported that highly correlated states of arousal, which may reflect failure to maintain a group-level regulatory baseline, occur in the context of stress, conflict, and relationship distress. Relationship strain may also place greater demands on neurocognitive regulatory processes. Just as allostatic load may be detrimental to individual health, social allostatic load may corrode relationship quality.

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