Putting the flight in "fight-or-flight": Testosterone reactivity to skydiving is modulated by autonomic activation.
Ontology highlight
ABSTRACT:
SUBMITTER: White SF
PROVIDER: S-EPMC6487482 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Flight represents a key trait in most insects, being energetically extremely demanding, yet often necessary for foraging and reproduction. Additionally, dispersal via flight is especially important for species living in fragmented landscapes. Even though, based on life-history theory, a negative relationship may be expected between flight and immunity, a number of previous studies have indicated flight to induce an increased immune response. In this study, we assessed whether induced immunity (i.e. immune gene expression) in response to 15-min forced flight treatment impacts individual survival of bacterial infection in the Glanville fritillary butterfly (Melitaea cinxia). We were able to confirm previous findings of flight-induced immune gene expression, but still observed substantially stronger effects on both gene expression levels and life span due to bacterial infection compared to flight treatment. Even though gene expression levels of some immunity-related genes were elevated due to flight, these individuals did not show increased survival of bacterial infection, indicating that flight-induced immune activation does not completely protect them from the negative effects of bacterial infection. Finally, an interaction between flight and immune treatment indicated a potential trade-off: flight treatment increased immune gene expression in naïve individuals only, whereas in infected individuals no increase in immune gene expression was induced by flight. Our results suggest that the up-regulation of immune genes upon flight is based on a general stress response rather than reflecting an adaptive response to cope with potential infections during flight or in new habitats.
| S-EPMC5347902 | biostudies-literature
Project description:Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.
| S-EPMC4398998 | biostudies-literature
Project description:Most disaster plans depend on using emergency physicians, nurses, emergency department support staff, and out-of-hospital personnel to maintain the health care system's front line during crises that involve personal risk to themselves or their families. Planners automatically assume that emergency health care workers will respond. However, we need to ask: Should they, and will they, work rather than flee? The answer involves basic moral and personal issues. This article identifies and examines the factors that influence health care workers' decisions in these situations. After reviewing physicians' response to past disasters and epidemics, we evaluate how much danger they actually faced. Next, we examine guidelines from medical professional organizations about physicians' duty to provide care despite personal risks, although we acknowledge that individuals will interpret and apply professional expectations and norms according to their own situation and values. The article goes on to articulate moral arguments for a duty to treat during disasters and social crises, as well as moral reasons that may limit or override such a duty. How fear influences behavior is examined, as are the institutional and social measures that can be taken to control fear and to encourage health professionals to provide treatment in crisis situations. Finally, the article emphasizes the importance of effective risk communication in enabling health care professionals and the public to make informed and defensible decisions during disasters. We conclude that the decision to stay or leave will ultimately depend on individuals' risk assessment and their value systems. Preparations for the next pandemic or disaster should include policies that encourage emergency physicians, who are inevitably among those at highest risk, to "stay and fight."
| S-EPMC7124291 | biostudies-literature
Project description:The oral pathogen Aggregatibacter actinomycetemcomitans (Aa) resides in infection sites with many microbes, including commensal streptococci such as Streptococcus gordonii (Sg). During infection, Sg promotes the virulence of Aa by producing its preferred carbon source, l-lactate, a phenomenon referred to as cross-feeding. However, as with many streptococci, Sg also produces high levels of the antimicrobial hydrogen peroxide (H2O2), leading to the question of how Aa deals with this potent antimicrobial during coinfection. Here, we show that Aa possesses two complementary responses to H2O2: a detoxification or fight response mediated by catalase (KatA) and a dispersion or flight response mediated by Dispersin B (DspB), an enzyme that dissolves Aa biofilms. Using a murine abscess infection model, we show that both of these responses are required for Sg to promote Aa virulence. Although the role of KatA is to detoxify H2O2 during coinfection, 3D spatial analysis of mixed infections revealed that DspB is required for Aa to spatially organize itself at an optimal distance (>4 µm) from Sg, which we propose allows cross-feeding but reduces exposure to inhibitory levels of H2O2. In addition, these behaviors benefit not only Aa but also Sg, suggesting that fight and flight stimulate the fitness of the community. These results reveal that an antimicrobial produced by a human commensal bacterium enhances the virulence of a pathogenic bacterium by modulating its spatial location in the infection site.
| S-EPMC4040543 | biostudies-literature
Project description:One of the most recognizable physiological phenomena is the adrenergic-induced fight-or-flight increase in heart rate and cardiac contraction. For the β-adenergic agonist-induced enhancement of calcium influx and transients, and contractility in the heart, we identify the dual requirement of a subpopulation of Rad-bound calcium channels under basal conditions and PKA phosphorylation of Rad. In mice expressing a non-phosphorylatable Rad mutant, basal cardiac contractility is reduced and adrenergic-augmentation of the calcium current and contractility are disabled. Expression of mutant calcium channel β-subunits that cannot bind the mutant Rad restored contractility, revealing a highly specific therapeutic approach to mimic the contractility imparted by adrenergic agonists. Our findings place Rad and its modulation of calcium channels at the nexus of adrenergic modulation of cardiac responses.
2022-03-20 | GSE198903 | GEO
Project description:The best understood "fight or flight" mechanism for increasing heart rate (HR) involves activation of a cyclic nucleotide-gated ion channel (HCN4) by beta-adrenergic receptor (betaAR) agonist stimulation. HCN4 conducts an inward "pacemaker" current (I(f)) that increases the sinoatrial nodal (SAN) cell membrane diastolic depolarization rate (DDR), leading to faster SAN action potential generation. Surprisingly, HCN4 knockout mice were recently shown to retain physiological HR increases with isoproterenol (ISO), suggesting that other I(f)-independent pathways are critical to SAN fight or flight responses. The multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) is a downstream signal in the betaAR pathway that activates Ca(2+) homeostatic proteins in ventricular myocardium. Mice with genetic, myocardial and SAN cell CaMKII inhibition have significantly slower HRs than controls during stress, leading us to hypothesize that CaMKII actions on SAN Ca(2+) homeostasis are critical for betaAR agonist responses in SAN. Here we show that CaMKII mediates ISO HR increases by targeting SAN cell Ca(2+) homeostasis. CaMKII inhibition prevents ISO effects on SAN Ca(2+) uptake and release from intracellular sarcoplasmic reticulum (SR) stores that are necessary for increasing DDR. CaMKII inhibition has no effect on the ISO response in SAN cells when SR Ca(2+) release is disabled and CaMKII inhibition is only effective at slowing HRs during betaAR stimulation. These studies show the tightly coupled, but previously unanticipated, relationship of CaMKII to the betaAR pathway in fight or flight physiology and establish CaMKII as a critical signaling molecule for physiological HR responses to catecholamines.
| S-EPMC2667018 | biostudies-literature
Project description:The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria. Neuroendocrine pathway genes are upregulated by intestinal bloating and are required for microbial aversion behavior. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. These results reveal how inputs from the intestine can aid in the recognition of a broad range of microbes and modulate host behavior via neuroendocrine signaling.
| S-EPMC6456415 | biostudies-literature
Project description:During the fight-or-flight response, the sympathetic nervous system stimulates L-type calcium ion (Ca2+) currents conducted by Ca(V)1 channels through activation of β-adrenergic receptors, adenylyl cyclase, and phosphorylation by adenosine 3',5'-monophosphate-dependent protein kinase [also known as protein kinase A (PKA)], increasing contractility of skeletal and cardiac muscles. We reconstituted this regulation of cardiac Ca(V)1.2 channels in non-muscle cells by forming an autoinhibitory signaling complex composed of Ca(V)1.2Δ1800 (a form of the channel truncated at the in vivo site of proteolytic processing), its noncovalently associated distal carboxyl-terminal domain, the auxiliary α₂δ₁ and β(2b) subunits, and A-kinase anchoring protein 15 (AKAP15). A factor of 3.6 range of Ca(V)1.2 channel activity was observed from a minimum in the presence of protein kinase inhibitors to a maximum upon activation of adenylyl cyclase. Basal Ca(V)1.2 channel activity in unstimulated cells was regulated by phosphorylation of serine-1700 and threonine-1704, two residues located at the interface between the distal and the proximal carboxyl-terminal regulatory domains, whereas further stimulation of channel activity through the PKA signaling pathway only required phosphorylation of serine-1700. Our results define a conceptual framework for Ca(V)1.2 channel regulation and identify sites of phosphorylation that regulate channel activity.
| S-EPMC3063709 | biostudies-literature
Project description:Compounds of main-group elements such as silicon are attractive candidates for green and inexpensive catalysts. For them to compete with state-of-the-art transition-metal complexes, new reactivity modes must be unlocked and controlled, which can be achieved through strain. Using a tris(2-skatyl)methylphosphonium ([TSMPH3 ]+ ) scaffold, we prepared the strained cationic silane [TSMPSiH]+ . In stark contrast with the generally hydridic Si-H bond character, it is acidic with an experimental pKa DMSO within 4.7-8.1, lower than in phenol, benzoic acid, and the few hydrosilanes with reported pKa values. We show that ring strain significantly contributes to this unusual acidity along with inductive and electrostatic effects. The conjugate base, TSMPSi, activates a THF molecule in the presence of CH-acids to generate a highly fluxional alkoxysilane via trace amounts of [TSMPSiH]+ functioning as a strain-release Lewis acid. This reaction involves a formal oxidation-state change from SiII to SiIV , presenting intriguing similarities with transition-metal-mediated processes.
| S-EPMC8252520 | biostudies-literature
Project description:Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. Despite decades of investigations, predominantly focusing on ryanodine receptor and phospholamban phosphorylation, the molecular mechanisms underlying the sympathetic nervous system control of cardiac contractility remain controversial and incompletely elucidated. Here, we identify the calcium-channel inhibitor Rad as a critical component. In cardiomyocytes isolated from knock-in mice expressing Rad with alanine-substitutions of the four PKA-phosphorylated serine residues (4SA-Rad), calcium currents cannot be increased by adrenergic agonists or phosphatase inhibitor. In these mice, basal cardiac contractility, exercise capacity and heart rate are reduced, and the augmentation of contractile force by adrenergic agonists is severely blunted. Expression of mutant calcium-channel β-subunits that cannot bind Rad is sufficient to restore calcium influx and cardiac contractility in 4SA-Rad mice to levels induced by adrenergic agonists in wild-type mice, revealing a potential therapeutic approach to enhance cardiac contractility while bypassing stimulation of adrenergic receptors.
2022-09-26 | PXD033492 | Pride