Stress Stimuli Research Articles

Inhibition of Glucocorticoid Synthesis by Metyrapone as an Approach to Study Their Contribution to Gastroprotection in Rats

—According to the results of our research glucocorticoids produced in response to ulcerogenic stress stimuli are gastroprotective factors. The aim of this review article is to demonstrate, through the analysis of data obtained in our studies, that the inhibition of glucocorticoid synthesis by metyrapone can be an adequate and valuable approach for studying the contribution of glucocorticoids, produced during acute activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, to gastroprotection in rats. When studying the contribution of glucocorticoids produced in response to moderate, normally non-ulcerogenic stressors or to the administration of the corticotropin-releasing factor (CRF) to gastroprotection, it was shown that the suppression of synthesis of these hormones by metyrapone leads to (1) the transformation of normally non-ulcerogenic stimuli into ulcerogenic ones; (2) the elimination of the gastroprotective effect of stress preconditioning; (3) the elimination of the gastroprotective effect of CRF. The effects of metyrapone were reproduced under conditions of suppressed glucocorticoid production using the selective CRF-1 receptor antagonist NBI 27914 and the blockage of glucocorticoid receptors with their antagonist RU38486. The data presented suggest that (a) glucocorticoids produced in response to moderate stress stimuli contribute to the protection of the gastric mucosa under these conditions and increase its resistance to subsequent ulcerogenic stimuli (i.e., they contribute to the gastroprotective effect of stress preconditioning); (b) glucocorticoids produced in response to CRF administration participate in the realization of its gastroprotective action. The data obtained confirm that the activation of the HPA axis is a gastroprotective component of stress response, and stress-produced glucocorticoids are important gastroprotective factors.

Defensive responses of most antioxidant genes in the freshwater dinoflagellate Palatinus apiculatus to cadmium stress and their implications

Defensive responses of most antioxidant genes in the freshwater dinoflagellate Palatinus apiculatus to cadmium stress and their implications

Comparative study of adaptive reserves of servicemen and servicemen-athletes with neuromuscular injuries after the post-acute rehabilitation

Purpose. To determine the level of adaptive reserves in servicemen and servicemen-athletes with injuries of the neuromuscular system at the end of the post-acute rehabilitation phase. Material & Methods. Twenty-two servicemen with identical injuries of the neuromuscular system were examined and divided into two groups. Group A included servicemen who used standard protocols for neuromuscular recovery during the post-acute rehabilitation phase. Group B consisted of servicemen-athletes who used standard protocols and rehabilitation techniques specific to their sports. Special physical exercises and a training regime were used to develop a test task for each study participant. The peculiarities of adaptative and compensatory reactions of servicemen to a physical stimulus were studied based on the results of heart rate variability (HRV), bioimpedansometry, and biochemical blood parameters (creatine phosphokinase, lactate dehydrogenase, testosterone, cortisol). Results. The bioimpedansometry results indicated that only servicemen of group B had body composition indicators that met morphometric norms. The initial HRV results of group A participants showed a high tension of heart rhythm regulation, and the autonomic balance was shifted towards sympathetic regulation. The basal cortisol level reached the upper limit of the norm, and testosterone was at the lower limit. After-exercise results demonstrated the strengthening of the central sinus rhythm regulation circuit. The cortisol concentration significantly decreased in the blood serum of group A servicemen in response to the stimulus, indicating compensatory reactions. The initial HRV spectral analysis parameters in group B subjects balanced the mechanisms of vago-sympathetic tone. In response to a stressful stimulus, the influence of autonomic regulation increased. The results of the biochemical blood tests for participants in group B specified the readaptation of the neuromuscular system and the recovery of the body’s adaptive reserves. Conclusions. The research results confirmed the necessity of finding new mechanisms to improve the rehabilitation of servicemen with neuromuscular system injuries starting from the post-acute rehabilitation phase. The effectiveness of incorporating sports rehabilitation training with modified kinematic characteristics, alongside anaerobic exercise, in the rehabilitation of servicemen was demonstrated.

Genome-wide identification and analysis of expression patterns of the ABC1K gene family members in Medicago sativa.

The ABC1K (activity of bc1 complex kinase) atypical protein kinase family regulates diverse physiological functions in plants, including the development, growth, and response of plants to various stress stimuli. However, to date, only a few members of the alfalfa (Medicago sativa) ABC1K gene family have been identified, which severely limits the exploration of the functional mechanism of alfalfa ABC1K. Here, we identified 22 ABC1K genes from the alfalfa genome and categorized them into four types on the basis of phylogenetic analysis results and gene structure. We then characterized the physical and biochemical properties, chromosomal location, subcellular localization, cis-regulatory elements, and conserved motifs of these genes. Transcript profiling analysis confirmed that MsABC1Ks were widely expressed in various alfalfa tissues, with tissue-specific expression. We also found that salt and drought conditions significantly regulated MsABC1K gene expression, thus indicating that MsABC1K genes perform critical functions in alfalfa's response to abiotic stress. In summary, the findings of our study serve as an important basis to enhance the stress resistance of alfalfa and provide valuable insights to better comprehend the functions of the MsABC1K gene family.

Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract

Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract

SP600125, a selective JNK inhibitor, is a potent inhibitor of NAD(P)H: quinone oxidoreductase 1 (NQO1).

The c-Jun N-terminal kinases (JNKs) has been identified as a critical modulator in multiple cellular processes, including stress stimulus, inflammation, cell proliferation, apoptosis, etc. SP600125 is a widely used ATP-competitive reversible JNKs inhibitor. NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoprotein mediated two or four electron-reduction of quinones. Here, we showed that SP600125 bind to the active pocket of NQO1 and inhibit NQO1 activity. SP600125 exhibits comparable inhibitory effects on NQO1-mediated quinone bioactivation, H2O2 generation, and cell death, as the specific NQO1 inhibitor dicoumarol (DIC). Importantly, the inhibitory effects of SP600125 on NQO1 are independent of JNKs inhibition. These results suggested that SP600125 is a novel NQO1 inhibitor, which provides new insights into the mechanism of action of SP600125. Furthermore, SP600125 should be used more cautiously as a JNKs inhibitor, especially when NQO1 is highly expressed. SP600125 competed with β-Lap (NQO1-bioactivated drugs) for binding to NQO1, and inhibited NQO1-dependent cell death.

Genome assembly of an endemic butterfly (Minois aurata) shed light on the genetic mechanisms underlying ecological adaptation to arid valley habitat

BackgroundThe Hengduan Mountains, one of the global biodiversity hotspots with exceptional species richness and high endemism, contains numerous arid valleys that create a distinctive geographical and ecological landscape. However, the adaptive evolutionary mechanisms of organism in the arid valley remain poorly understood. Minois aurata, an endemic butterfly species found exclusively in the arid valley of the upper Minjiang River, represents an attractive model system for studying adaptive evolutionary mechanisms to arid valley environments.ResultsHere, we present the first chromosome-level genome assembly for Minois aurata, with a total size of approximately 609.17 Mb, and a scaffold N50 size of 23.88 Mb. These scaffolds were further clustered and anchored onto 29 chromosomes based on Hi-C data. A total of 16,163 protein-coding genes were predicted, of which 91.83% were functionally annotated. The expansion of transposable elements (TEs) accounts for the relatively large genome size of M. aurata, potentially aiding its adaptation to environmental conditions. Phylogenomic analyses based on 3,785 single-copy genes revealed that M. aurata is most closely related to Hipparchia semele. Further mitochondrial genome analysis of four Minois species placed M. aurata in a basal position within the genus, supporting it as an independent species. A total of 185 rapidly evolving and 232 specific gene families were identified in M. aurata. Functional enrichment analysis indicated that these gene families were mainly associated with ultraviolet radiation, heat and hypoxia responses. We also identified 234 positive selected genes in M. aurata, some of which are related to compound eye photoreceptor development, osmotic stress, and light stimulus response. Demographic analysis indicated that the effective population size of M. aurata decreased around 0.4 and 0.04 million years ago, respectively, coinciding with the localized sub-glaciation.ConclusionThe chromosome-level genome offers a comprehensive genomic basis for understanding the evolutionary and adaptive strategies of Minois aurata in the unique arid valley environment of the Hengduan Mountains, while also providing valuable insights into the broader mechanisms of organism adaptation to such habitats.

Identification of DAF-16/FOXO Binding Partners in Caenorhabditis elegans by Immunoprecipitation and Mass Spectrometry.

The conserved transcription factor DAF-16/FOXO is a central hub in the regulation of stress responses and aging. It was first discovered as a protein activated by reduced insulin/IGF-like signaling (IIS) that would drive aging-preventive transcriptional outcomes. However, research from the last two decades has shown that its functions extend much further, with it responding to a broad spectrum of stress and deprivation-related stimuli and relaying them into optimal transcriptional outcomes that promote stress resistance, slow aging, and ultimately help the organism to survive each given threat. Evidence is mounting that DAF-16/FOXO is not self-sufficient in this important role but relies on numerous binding partners that help it achieve appropriate activity and target gene selectivity, with prominent examples being the chromatin remodeling complex SWI/SNF, the DAF-16-inhibitory protein HCF-1, or the transcription factor HLH-30/TFEB-just to mention a few. Here we present a protocol for the identification of such DAF-16/FOXO binding partners in Caenorhabditis elegans, comprising the large-scale growth and harvest of such animals, their lysis, and the eventual purification of DAF-16/FOXO, to yield samples that can be analyzed for co-purifying proteins und thus potentialbinding partners by tandem mass spectrometry.

Effectiveness of virtual reality glasses with integrated sign language in reducing dental anxiety during pulpotomy in children with hearing impairment: a randomized controlled trial

BackgroundChildren with hearing impairment (HI) face communication challenges during dental procedures due to hearing loss. Studies suggest that distraction techniques, like virtual reality (VR), can effectively divert their focus from stressful stimuli, resulting in a more comfortable dental experience. The present study aims to assess the effectiveness of distracting children with moderate to severe (HI) with virtual reality glasses that show cartoons in sign language during pulpotomy treatment compared to conventional management techniques.MethodsForty children aged five to seven participated in a randomized controlled parallel two-arm clinical trial—the type of behavioral management employed determined which two groups children were randomly placed into. Group I (Study group) used virtual reality glasses as a diversion, while Group II (Control group) used the conventional behavior management approach. Local anesthesia was administrated, and a pulpotomy procedure was performed on the selected tooth, followed by stainless steel crown restoration (SSC). There were three methods used to assess dental anxiety before and after the procedure: the physiological method, which used heart rate (HR); the objective measure, which used the Venham Clinical Anxiety Scale (VCAS); and the subjective measure, which used the modified Facial Affective Scale (FAS). An independent t-test was employed for HR analysis of the difference between the groups as a continuous variable. The Pearson Chi-square test assessed differences between groups for categorical variables, such as (VCAS) (FAS).ResultsNo significant differences were found in mean (HR) or (VCAS) between the two groups throughout the procedures: during local anesthesia (p = 0.659, 0.282), pulpotomy (p = 0.482, 0.451), and stainless steel crown preparation (p = 0.090, 0.284). Anxiety levels by (FAS) remained statistically comparable between the two groups before and after the procedures (p = 0.507, 0.749), respectively.ConclusionsThe use of VR glasses revealed no significant advantages in managing children with HI during the dental visit compared to the conventional method of child behavior management.Trial registrationThe trial was prospectively enrolled on 11/11/2023 under the identification number NCT06153823 on ClinicalTrials.gov.

Analysis of abiotic and biotic stress-induced Ca2+ transients in the crop species Solanum tuberosum

Secondary messengers, such as calcium ions (Ca2+), are integral parts of a system that transduces environmental stimuli into appropriate cellular responses. Different abiotic and biotic stresses as well as developmental processes trigger temporal increases in cytosolic free Ca2+ levels by an influx from external and internal stores. Stimulus-specificity is obtained by a certain amplitude, duration, oscillation and localisation of the response. Most knowledge on stress-specific Ca2+ transient, called calcium signatures, has been gained in the model plant Arabidopsis thaliana, while reports about stress-related Ca2+ signalling in crop plants are comparatively scarce. In this study, we introduced the Ca2+ biosensor apoaequorin into potato (Solanum tuberosum, Lcv. Désirée). We observed dose-dependent calcium signatures in response to a series of stress stimuli, including H2O2, NaCl, mannitol and pathogen-associated molecular patterns (PAMPs) with stimuli-specific kinetics. Direct comparison with Arabidopsis revealed differences in the kinetics and amplitude of Ca2+ transients between both species, implying species-specific sensitivity for different stress conditions. The potato line generated in this work provides a useful tool for further investigations on stress-induced signalling pathways, which could contribute to the generation of novel, stress-tolerant potato varieties.

Unraveling the Drivers of the Stress Granule Signature in Splicing Factor-Mutant Myeloid Malignancies

Unraveling the Drivers of the Stress Granule Signature in Splicing Factor-Mutant Myeloid Malignancies

Stress survival and longevity of Caenorhabditis elegans lacking NCS-1.

Although dysfunctional Ca2+ signaling can trigger biochemical reactions that lead to cell death, the role of calcium-binding proteins (CBPs) in this process is still a topic of debate. Neuronal calcium sensor 1 (NCS-1) is a CBP that is highly conserved and has been shown to increase cell survival against various types of injuries. As such, we hypothesized that NCS-1 could also be a stress-responsive protein with potential effects on survival and longevity. To explore this possibility, we conducted experiments to examine how Caenorhabditis elegans ncs-1 mutant nematodes fared under three different stress conditions: hyperosmotic, thermal, and chemical oxidant challenges. Our results showed that while the lack of NCS-1 had no effect on survival responses to hyperosmotic and thermal stresses, ncs-1 worms demonstrated remarkable resistance to the oxidant paraquat in a dose-dependent manner. Based on these findings, we conclude that C. elegans may employ adaptive mechanisms in the absence of NCS-1 to survive specific oxidative stress stimuli.

New insights into the evolution analysis of trihelix gene family in eggplant (Solanum melongena L.) and expression analysis under abiotic stress.

Trihliex transcription factors (TFs) play crucial roles in plant growth and development, stress response, and plant hormone signaling network transmission. In order to comprehensively investigate the functions of trihliex genes in eggplant development and the abiotic stress response, we conducted an extensive analysis of the trihliex gene family in the eggplant genome. In this study, 30 trihelix gene family members were unevenly distributed on 12 chromosomes. On the basis of their phylogenetic relationships, these genes were conserved in different plant species and could be divided into six subfamilies, with trihelix genes within the same subfamily sharing similar structures. The promoter regions of trihelix genes contained cis-acting elements related to plant growth and development, plant hormones, and abiotic stress responses, suggesting potential applications in the development of more resistant crops. Selective pressure assessments indicated that trihliex genes have undergone purifying selection pressure. Expression analysis on the basis of transcriptomic profiles revealed that SmGT18, SmGT29, SmGT6, and SmGT28 are highly expressed in roots, leaves, flowers, and fruits, respectively. Expression analysis via quantitative real-time PCR (qRT‒PCR) revealed that most trihelix genes respond to low temperature, abscisic acid (ABA), and salicylic acid (SA), with SmGT29 exhibiting significant upregulation under cold stress conditions. The SmGT29 gene was subsequently successfully cloned from eggplant, which was located in the nucleus, robust transcriptional activity, and a protein molecular weight of 74.59kDa. On the basis of these findings, SmGT29 was postulated to be a pivotal candidate gene that actively responds to biotic stress stimuli, thereby supporting the plant's innate stress resistance mechanisms. In summary, this study was the first report on trihelix genes and their potential roles in eggplant plants. These results provided valuable insights for enhancing stress resistance and quality traits in eggplant breeding, thereby serving as a crucial reference for future improvement efforts.

Characterization of the C5H11ORF96 gene in chickens: cloning, tissue distribution and investigation of its potential function in stress response regulation

Characterization of the C5H11ORF96 gene in chickens: cloning, tissue distribution and investigation of its potential function in stress response regulation

Abnormal Autonomic Nervous Regulation in Patients with Globus Pharyngeus.

Globus pharyngeus could be described as a benign sensation of lump or foreign object in the throat. The etiology of the globus as a solitary syndrome is still unknown, but it is proposed that stress could have an important role in symptom emergence. To evaluate the autonomic nervous regulation in patients with globus compared to healthy controls in reaction to stress. Patients included in the study were diagnosed based on ROME IV criteria for Disorders of Gut Brain Interaction. Besides globus, the patients did not suffer any other substantial medical condition. As a control group, measurement of healthy volunteers was performed. Both groups underwent the same stress protocol assessment in the same laboratory settings. The protocol consist of two types of stressors: cold pressor test and mental arithmetic test to test different types of autonomic reactivity. Baroreflex sensitivity was significantly decreased in patients compared to controls in all phases of the protocol. Low-frequency band of systolic blood pressure variability was significantly increasedduring both stress phases in patients compared to controls. High-frequency band of heart rate variability was significantly decreased in patients compared to controls during the both of the stress phases. The results of this study shows discrete abnormalities in complex autonomic reflex control which are predominantly manifested in response to stressful stimuli indicating altered neurocardiac regulation as a reaction to stress associated with globus pharynegus. This fact could have an important role in the personalized management of globus patients such as biofeedback.

Bidirectional Control of Emotional Behaviors by Excitatory and Inhibitory Neurons in the Orbitofrontal Cortex.

The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear. This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.

Characterization of a rapid avoidance behavior in Manduca sexta larvae in response to noxious stimuli.

This study focuses on the nociceptive responses observed in the tobacco hornworm (Manduca sexta). While prior investigations have described the sensory neurons and muscle activation patterns associated with the 'strike' behavior, there remains a gap in our understanding of the alternative 'withdrawal' movement, wherein the animal bends its head and thorax away from the stimulus. Our results show that stimulus location determines which nocifensive behavior is elicited. Interestingly, stimulation of specific mid-body segments could result in either withdrawal or strike, indicating a decision process rather than a hard-wired circuit. The withdrawal behavior was characterized using high-speed videography and electromyography. The results show that withdrawal in M. sexta is driven by contralateral ventral muscles, followed by an increase in ipsilateral muscle activation just before the bending stops. Dorsal muscles are co-activated throughout the movement. Although both withdrawal and strike behaviors involve sequential activation of lateral muscles, these behaviors involve different muscle groups. This discovery provides a novel model system to investigate the context dependence and decision-making processes triggered by stressful or noxious stimuli.

Activation of the general stress response sigma factor SigB prevents competence development in Bacillus subtilis.

Bacillus subtilis exhibits a large number of different specific and general adaptation reactions, which need to be well balanced to sustain survival under largely unfavorable conditions. Under specific conditions, natural competence develops, which enables B. subtilis to actively take up exogenous DNA to integrate it into its own genome. In contrast to this specific adaptation, the general stress response is induced by a variety of exogenous stress and starvation stimuli, providing comprehensive protection and enabling survival of vegetative B. subtilis cells. In the present work, we reveal the molecular basis for the interconnection of these two important responses in the regulatory network. We describe that the master regulator of the general stress response SigB is activated by physiological stress stimuli, including daylight and ethanol stress, leading to the inactivation of the competence master regulator ComK by transcriptional anti-sense regulation, showing a strict hierarchy of adaptational responses under severe stress.

The Complement System as a Part of Immunometabolic Post-Exercise Response in Adipose and Muscle Tissue.

The precise molecular processes underlying the complement's activation, which follows exposure to physical stress still remain to be fully elucidated. However, some possible mechanisms could play a role in initiating changes in the complement's activity, which are observed post-exposure to physical stress stimuli. These are mainly based on metabolic shifts that occur in the microenvironment of muscle tissue while performing its function with increased intensity, as well as the adipose tissue's role in sterile inflammation and adipokine secretion. This review aims to discuss the current opinions on the possible link between the complement activation and diet, age, sex, and health disorders with a particular emphasis on endocrinopathies and, furthermore, the type of physical activity and overall physical fitness. It has been indicated that regular physical activity incorporated into therapeutic strategies potentially improves the management of particular diseases, such as, e.g., autoimmune conditions. Moreover, it represents a favorable influence on immunoaging processes. A better understanding of the complement system's interaction with physical activity will support established clinical therapies targeting complement components.

Stress Can Induce Bovine Alpha-Herpesvirus 1 (BoHV-1) Reactivation from Latency.

Bovine alpha-herpesvirus 1 (BoHV-1) is a significant problem for the cattle industry, in part because the virus establishes latency, and stressful stimuli increase the incidence of reactivation from latency. Sensory neurons in trigeminal ganglia and unknown cells in pharyngeal tonsils are importantsites for latency. Reactivation from latency can lead to reproductive problems in pregnant cows, virus transmission to young calves, suppression of immune responses, and bacterial pneumonia. BoHV-1 is also a significant cofactor in bovine respiratory disease (BRD). Stress, as mimicked by the synthetic corticosteroid dexamethasone, reproducibly initiates reactivation from latency. Stress-mediated activation of the glucocorticoid receptor (GR) stimulates viral replication and transactivation of viral promoters that drive the expression of infected cell protein 0 (bICP0) and bICP4. Notably, GR and Krüppel-like factor 15 (KLF15) form a feed-forward transcription loop that cooperatively transactivates immediate early transcription unit 1 (IEtu1 promoter). Two pioneer transcription factors, GR and KLF4, cooperatively transactivate the bICP0 early promoter. Pioneer transcription factors bind silent viral heterochromatin, remodel chromatin, and activate gene expression. Thus, wepredict that these novel transcription factors mediate early stages of BoHV-1 reactivation from latency.