scholarly journals Inflammatory Amplification: A Central Tenet of Uterine Transition for Labor

2021 ◽  
Vol 11 ◽  
Author(s):  
Kelycia B. Leimert ◽  
Wendy Xu ◽  
Magdalena M. Princ ◽  
Sylvain Chemtob ◽  
David M. Olson
Keyword(s):  
Preterm Birth ◽  
Positive Feedback ◽  
Autocrine Signaling ◽  
Physiological Processes ◽  
Inflammatory Signals ◽  
Therapeutic Value ◽  
Central Tenet ◽  
Key Players ◽  
Signaling Interactions ◽  
Compare And Contrast

In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterine cell and tissue. The amplification events occur in parallel until they reach a certain threshold, ‘tipping the scale’ and contributing to processes of uterine activation and functional progesterone withdrawal. The described signaling interactions all occur upstream from the presentation of clinical labor symptoms. In this review, we will: 1) describe the different physiological processes involved in uterine transition for each intrauterine tissue; 2) compare and contrast the current models of labor initiation; 3) introduce innovative models for measuring paracrine inflammatory interactions; and 4) discuss the therapeutic value in identifying and targeting key players in this crucial event for preterm birth.

scholarly journals Understanding sex differences in long-term blood pressure regulation: insights from experimental studies and computational modeling

2019 ◽  
Vol 316 (5) ◽  
pp. H1113-H1123 ◽  
Author(s):  
Sameed Ahmed ◽  
Rui Hu ◽  
Jessica Leete ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Computational Models ◽  
Experimental Studies ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Physiological Processes ◽  
Key Players

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computational models. In this review, we describe published computational models that represent key players in blood pressure regulation, and highlight sex-specific models and their findings.

scholarly journals Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop

2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Autocrine Signaling ◽  
Positive Feedback Loop ◽  
Short Term Plasticity ◽  
Extracellular Signaling ◽  
Presynaptic Protein ◽  
Long Term Facilitation

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.

scholarly journals Discovery of Glucocorticoid Receptor-β in Mice with a Role in Metabolism

2010 ◽  
Vol 24 (9) ◽  
pp. 1715-1727 ◽  
Author(s):  
Terry D. Hinds ◽  
Sadeesh Ramakrishnan ◽  
Harrison A. Cash ◽  
Lance A. Stechschulte ◽  
Garrett Heinrich ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hairpin Rna ◽  
Culture Cells ◽  
Physiological Processes ◽  
Inflammatory Signals ◽  
Tissue Culture Cells ◽  
Rigorous Testing ◽  
Murine Tissue ◽  
Exon 9 ◽  
Rna Knockdown

Abstract Glucocorticoid hormones control diverse physiological processes, including metabolism and immunity, by activating the major glucocorticoid receptor (GR) isoform, GRα. However, humans express an alternative isoform, human (h)GRβ, that acts as an inhibitor of hGRα to produce a state of glucocorticoid resistance. Indeed, evidence exists that hGRβ contributes to many diseases and resistance to glucocorticoid hormone therapy. However, rigorous testing of the GRβ contribution has not been possible, because rodents, especially mice, are not thought to express the β-isoform. Here, we report expression of GRβ mRNA and protein in the mouse. The mGRβ isoform arises from a distinct alternative splicing mechanism utilizing intron 8, rather than exon 9 as in humans. The splicing event produces a form of β that is similar in structure and functionality to hGRβ. Mouse (m)GRβ has a degenerate C-terminal region that is the same size as hGRβ. Using a variety of newly developed tools, such as a mGRβ-specific antibody and constructs for overexpression and short hairpin RNA knockdown, we demonstrate that mGRβ cannot bind dexamethasone agonist, is inhibitory of mGRα, and is up-regulated by inflammatory signals. These properties are the same as reported for hGRβ. Additionally, novel data is presented that mGRβ is involved in metabolism. When murine tissue culture cells are treated with insulin, no effect on mGRα expression was observed, but GRβ was elevated. In mice subjected to fasting-refeeding, a large increase of GRβ was seen in the liver, whereas mGRα was unchanged. This work uncovers the much-needed rodent model of GRβ for investigations of physiology and disease.

Estrogen regulation of the molecular phenotype and active translatome of AVPV kisspeptin neurons

Endocrinology ◽  
2021 ◽  
Author(s):  
Shannon B Z Stephens ◽  
Alexander S Kauffman
Keyword(s):  
Positive Feedback ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Feedback Regulation ◽  
Rna Seq ◽  
Molecular Phenotype ◽  
Estrogen Regulation ◽  
Physiological Processes ◽  
Estrogen Effects

Abstract In females, ovarian estradiol (E2) exerts both negative and positive feedback regulation on the neural circuits governing reproductive hormone secretion, but the cellular and molecular mechanisms underlying this remain poorly understood. In rodents, ERα-expressing kisspeptin neurons in the hypothalamic anteroventral periventricular region (AVPV) are prime candidates to mediate E2 positive feedback induction of preovulatory GnRH and LH surges. E2 stimulates AVPV Kiss1 expression, but the full extent of estrogen effects in these neurons is unknown; whether E2 stimulates or inhibits other genes in AVPV Kiss1 cells has not been determined. Indeed, understanding of the function(s) of AVPV kisspeptin cells is limited, in part, by minimal knowledge of their overall molecular phenotype, as only a few genes are currently known to be co-expressed in AVPV Kiss1 cells. To provide a more detailed profiling of co-expressed genes in AVPV Kiss1 cells, including receptors and other signaling factors, and test how these genes respond to E2, we selectively isolated actively-translated mRNAs from AVPV Kiss1 cells of female mice and performed RNA-Seq. This identified >13,000 mRNAs co-expressed in AVPV Kiss1 cells, including multiple receptor and ligand transcripts positively or negatively regulated by E2. We also performed RNAscope to validate high co-expression of several transcripts identified by RNA-Seq, including Pdyn (prodynorphin), Penk (proenkephalin), Vgf (VGF), and Cartpt (CART), in female AVPV Kiss1 cells. Given the important role of AVPV kisspeptin cells in positive feedback, E2 effects on identified genes may relate to the LH surge mechanism and/or other physiological processes involving these AVPV kisspeptin cells.

scholarly journals Structural insights into the mechanisms of CNBD channel function

2017 ◽  
Vol 150 (2) ◽  
pp. 225-244 ◽  
Author(s):  
Zachary M. James ◽  
William N. Zagotta
Keyword(s):  
Cyclic Nucleotide ◽  
Ion Selectivity ◽  
K Channel ◽  
Hcn Channels ◽  
Nucleotide Binding Domain ◽  
Physiological Processes ◽  
Structural Framework ◽  
Voltage Dependent ◽  
Compare And Contrast ◽  
Structural Insights

Cyclic nucleotide-binding domain (CNBD) channels are a family of ion channels in the voltage-gated K+ channel superfamily that play crucial roles in many physiological processes. CNBD channels are structurally similar but functionally very diverse. This family includes three subfamilies: (1) the cyclic nucleotide-gated (CNG) channels, which are cation-nonselective, voltage-independent, and cyclic nucleotide-gated; (2) the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are weakly K+ selective, hyperpolarization-activated, and cyclic nucleotide-gated; and (3) the ether-à-go-go-type (KCNH) channels, which are strongly K+ selective, depolarization-activated, and cyclic nucleotide-independent. Recently, several high-resolution structures have been reported for intact CNBD channels, providing a structural framework to better understand their diverse function. In this review, we compare and contrast the recent structures and discuss how they inform our understanding of ion selectivity, voltage-dependent gating, and cyclic nucleotide–dependent gating within this channel family.

scholarly journals Anterograde and retrograde signaling by an Aplysia neurotrophin forms a transsynaptic functional unit

2018 ◽  
Vol 115 (46) ◽  
pp. E10951-E10960 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Stefan Kassabov ◽  
Stylianos Kosmidis ◽  
Huixiang Zhu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Functional Unit ◽  
Companion Paper ◽  
Retrograde Signaling ◽  
Autocrine Signaling ◽  
Cellular Functions ◽  
Short Term ◽  
Positive Feedback Loop

Whereas short-term synaptic plasticity is often either pre- or postsynaptic, intermediate- and long-term plasticity generally require coordinated pre- and postsynaptic mechanisms. Thus, the transition from presynaptic short-term facilitation (STF) to intermediate-term facilitation (ITF) induced by 5HT at Aplysia sensory-to-motor neuron synapses requires the recruitment of postsynaptic mechanisms and activation of protein synthesis in both neurons. In the companion paper to this report, we found that presynaptic autocrine signaling by an Aplysia neurotrophin (ApNT) forms a positive feedback loop that drives the synapses from STF to ITF. Here we report that ApNT also acts through both anterograde and retrograde signaling to form a transsynaptic positive feedback loop that orchestrates cellular functions in both the presynaptic and postsynaptic neurons during the induction of ITF. These two feedback loops activate protein synthesis in each synaptic compartment, which in both cases depends on signaling from the other synaptic compartment. These results suggest that the pre- and postsynaptic compartments act as one functional unit during the consolidation of learning-related facilitation induced by 5HT.

scholarly journals Circadian Clocks and the Interaction between Stress Axis and Adipose Function

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Isa Kolbe ◽  
Rebecca Dumbell ◽  
Henrik Oster
Keyword(s):  
Stress Responses ◽  
Metabolic Disorders ◽  
Stress Hormones ◽  
Circadian Clocks ◽  
Stress Disorders ◽  
Stress Axis ◽  
Physiological Conditions ◽  
Physiological Processes ◽  
Key Players ◽  
Adipose Cells

Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.

The endocannabinoid system

2020 ◽  
Vol 64 (3) ◽  
pp. 485-499
Author(s):  
Aruna Kilaru ◽  
Kent D. Chapman
Keyword(s):  
Signaling Pathways ◽  
Membrane Lipids ◽  
Endocannabinoid System ◽  
Physiological Processes ◽  
Therapeutic Value ◽  
Wide Range ◽  
Therapeutic Development ◽  
The Central Nervous System ◽  
Psychotropic Effects ◽  
Signaling Process

Abstract Thirty years ago, the discovery of a cannabinoid (CB) receptor that interacts with the psychoactive compound in Cannabis led to the identification of anandamide, an endogenous receptor ligand or endocannabinoid. Research on endocannabinoids has since exploded, and additional receptors along with their lipid mediators and signaling pathways continue to be revealed. Specifically, in humans, the release of endocannabinoids from membrane lipids occurs on demand and the signaling process is rapidly attenuated by the breakdown of the ligand suggesting a tight regulation of the endocannabinoid system (ECS). Additionally, the varying distribution of CB receptors between the central nervous system and other tissues allows for the ECS to participate in a wide range of cognitive and physiological processes. Select plant-derived ‘phyto’cannabinoids such as Δ-9-tetrahydrocannabinol (Δ9-THC) bind to the CB receptors and trigger the ECS, and in the case of Δ9-THC, while it has therapeutic value, can also produce detrimental effects. Current research is aimed at the identification of additional phytocannabinoids with minimal psychotropic effects with potential for therapeutic development. Although decades of research on the ECS and its components have expanded our understanding of the mechanisms and implications of endocannabinoid signaling in mammals, it continues to evolve. Here, we provide a brief overview of the ECS and its overlap with other related lipid-mediated signaling pathways.

Human rights and nursing codes of ethics in Canada 1953–2017

2020 ◽  
Vol 27 (4) ◽  
pp. 1077-1088
Author(s):  
Dawn Tisdale ◽  
Paisly Michele Symenuk
Keyword(s):  
Human Rights ◽  
Codes Of Ethics ◽  
Well Being ◽  
Ethical Framework ◽  
Historical Method ◽  
Central Tenet ◽  
Canadian Context ◽  
Protection Of Human Rights ◽  
Compare And Contrast ◽  
Health And Well Being

Human rights are foundational to the health and well-being of all individuals and have remained a central tenet of nursing’s ethical framework throughout history. The purpose of this study is to explore continuity and changes to human rights in nursing codes of ethics in the Canadian context. This study examines nursing codes of ethics between the years 1953 and 2017, which spans the very first code in Canada to the most recently adopted. The historical method is used to compare and contrast human rights language, positioning and descriptions between different code editions. The findings suggest there has been very little change in how human rights have been included within the Canadian nursing codes of ethics. Furthermore, we consider how changes within the nursing profession have influenced the authority of codes of ethics and their ability to support nurses in carrying out ethical obligations specific to human rights. Finally, the impacts and implications of these changes are discussed concerning the protection of human rights in today’s healthcare landscape in Canada.

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