Stress Response System Research Articles

Ethanol fermentation by saprotrophic white-rot fungus Phanerochaete sordida YK-624 during wood decay as a system for short-term resistance to hypoxic conditions

In this study, major factors involved in regulating ethanol production from wood by the saprotrophic white-rot fungus Phanerochaete sordida YK-624 were investigated. P.sordida YK-624 produced ethanol from wood meal culture without the addition of any nutrients, and ethanol was produced from wood culture only when the oxygen concentration in headspace was reduced to ≤5%; thereafter, ethanol production ceased within a few days. Analyses of gene expression during aerobic incubation indicated that P.sordida simultaneously upregulates the glycolytic pathway from sugar uptake to pyruvate conversion during ethanol fermentation and suppresses pyruvate influx into the TCA cycle. Upon termination of ethanol fermentation, the expression of all tested genes was repressed, and the fungus ceased to grow. In contrast, the fungus could utilize ethanol for aerobic growth. These results suggest that ethanol fermentation by P.sordida functions as a short-term stress response system under anaerobic conditions during wood decay, enabling the fungus to rapidly resume growing when oxygen is supplied (e.g., following breakdown of plant cell walls or removal of the fungus from water immersion). This is the first report to describe the physiologic significance of ethanol fermentation in saprotrophic white-rot fungi.

Living Dangerously: Protective and Harmful ER Stress Responses in Pancreatic β-Cells.

Type 2 diabetes (T2D) is a growing cause of poor health, psychosocial burden, and economic costs worldwide. The pancreatic β-cell is a cornerstone of metabolic physiology. Insulin deficiency leads to hyperglycemia, which was fatal before the availability of therapeutic insulins; even partial deficiency of insulin leads to diabetes in the context of insulin resistance. Comprising only an estimated 1 g or <1/500th of a percent of the human body mass, pancreatic β-cells of the islets of Langerhans are a vulnerable link in metabolism. Proinsulin production constitutes a major load on β-cell endoplasmic reticulum (ER), and decompensated ER stress is a cause of β-cell failure and loss in both type 1 diabetes (T1D) and T2D. The unfolded protein response (UPR), the principal ER stress response system, is critical for maintenance of β-cell health. Successful UPR guides expansion of ER protein folding capacity and increased β-cell number through survival pathways and cell replication. However, in some cases the ER stress response can cause collateral β-cell damage and may even contribute to diabetes pathogenesis. Here we review the known beneficial and harmful effects of UPR pathways in pancreatic β-cells. Improved understanding of this stress response tipping point may lead to approaches to maintain β-cell health and function.

Peripheral molecular messages – cytokines and stress hormones – in the context of cognitive aging phenotypes: healthy ageing/depression/dementia

Over last years, the world’s aging populations are rising rapidly, and the phenotypes of cognitive insufficiency, such as old age, depression and dementia, are increasing. Search for approaches to discrimination between such phenotypes is extremely relevant. Current studies present compelling evidence of the key role of immune system (its peripheral compartment), and the stress response system in physiological brain health. Therefore, assessment of complex interactions between immune and neuroendocrine systems may be an effective way to differentiate between depression and early stages of dementia in elderly people. Our purpose was to reveal peripheral molecular messages, e.g., cytokines and stress hormones, in the context of cognitive impairment phenotypes: healthy old age/old age depression/dementia. Eighty elderly people were included into groups as follows: “Healthy ageing”, “Dementia”, “Depression”. Levels of certain cytokines: IL-6, IL-1β, TNFα, IFNγ, IL-10, and stress hormones (cortisol, ACTH, dopamine, noradrenaline, and adrenaline) were determined in blood plasma by ELISA. The intergroup differences were evaluated by the Kruskal-Wallis test with Conover-Inman post-hoc pairwise comparisons. For differential diagnostics between the groups of elderly people with varying grades of cognitive impairment, we used linear canonical discriminant analysis performed on the ranks. It has been shown that cognitive insufficiency phenotypes—old age depression and dementia—differ from the healthy ageing phenotype with their high peripheral levels of TNFα cytokine and low levels of IL-1β. The differences between depression in elderly and dementia included lower level of IL-10 in depression (lower than in “Healthy ageing”), and high IL-6 in dementia (compared to “Healthy ageing”). Evaluation of the hypothalamic-pituitary and sympatho-adreno-medullary axes hormones showed hyporesponsiveness of hypothalamic-pituitary axis, regardless of cognitive insufficiency phenotypes, along with activation of sympatho-adreno-medullary axis, i.e., high dopamine level in old age depression with dementia, and high adrenaline level in dementia, than in depression of elderly phenotype and healthy ageing. Such significant differences in the levels of molecular messages, i.e., cytokines and stress hormones among the old age person groups, enabled diagnostic efficacy of 87.5% to differentiate cognitive phenotypes of aging: healthy ageing, old age depression, and dementia.

Acute Response of Stress System in Multiple Sclerosis

Background: It has long been suspected that exposure to stress is a major factor that can increase the risk of Multiple Sclerosis (MS) and exacerbate it, as a stress-related disorder. Therefore, we conducted this study to investigate the response of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullar (SAM) system to acute social stress. Methods: A total of 46 MS patients and 23 age-sex-matched healthy controls were recruited in the study. The Trier Social Stress Test (TSST) was used to induce acute psychosocial stress. We measured salivary cortisol (SC) to evaluate the HPA axis. In addition, electrocardiography (ECG) was recorded to evaluate the SAM system based on the linear and non-linear features of Heart Rate Variation (HRV). Then, SC and HRV were measured before and after the stress exposure. We also used the Depression Anxiety Stress Scale (DASS) and Emotional Visual Analog Scale (EVAS) to conduct the psychometric assessment and evaluate the perceived stress level, respectively. Results: The mean age of the MS group was 35.38 ± 15 years, with a mean disease duration of 7.4 ± 60. Besides, the HC group's mean age was 35.8 ± 9 years. There were no significant differences in demographic features and DASS scores between the two groups. In response to TSST, both MS and healthy individuals showed a significant increase in the SC levels and EVAS scores, as well as changes in the HRV indices. Notably, significant differences were also found between the two groups regarding the basic and post-stress SC levels, EVAS score, and HRV indices. Unlike the HC group, the SC level returned to its baseline after recovery in the MS group, and the sympathetic tone was more sensitive. Conclusions: Our results indicated that both MS and healthy individuals respond to acute stress regarding neuroendocrine assessment; however, patients with multiple sclerosis show some impairments in this response.

Dynamics of diurnal cortisol and alpha-amylase secretion and their associations with PTSD onset in recent interpersonal trauma survivors.

Dysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs). Using a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up. Multilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase. Results suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.

Alcoholic liver disease: Current insights into cellular mechanisms.

Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated. Oxidative stress, mitochondrial dysfunction, gut dysbiosis and altered immune system response plays an important role in disease pathogenesis, triggering the activation of inflammatory pathways and apoptosis. Despite many recent clinical studies treatment options for ALD are limited, especially at the alcoholic hepatitis stage. We have therefore reviewed some of the key pathways involved in the pathogenesis of ALD and highlighted current trials for treating patients.

Associations between inertia of negative emotions and diurnal cortisol in a sample of college students

Emotional inertia refers to the extent to which emotional states are predictable over time and are resistant to change. High emotional inertia, characterized by emotional states that carry over from one moment to the next, has been linked with both psychological maladjustment and impaired emotion regulation abilities. However, little research has examined the psychobiological correlates of emotional inertia. As such, in this study, we examined the association between inertia of negative emotions with cortisol, the end product of the hypothalamic pituitary adrenal (HPA) axis, one of the body’s primary stress response systems. Participants were 76 college students (24% male, Mage=18.53, SD=0.37), who completed five corresponding daily diaries and salivary samples to ascertain cortisol per day for 3 consecutive days. Hierarchical linear models indicated that greater inertia of negative emotion across the three days was associated with smaller cortisol awakening responses (CAR) and lower AUCg, even when controlling for average negative emotion and momentary stress perception. There were no associations with the diurnal cortisol slope. These findings shed light on the neurobiological mechanisms involved in emotion dynamics.

Clinical Measures of Allostatic Load in Children and Adolescents with Food Allergy, Depression, or Anxiety

PurposeSustained high stress exposure results in chronic activation of the stress response system, dysregulated stress responses, high allostatic load, and poor later-life health. Children and adolescents with chronic health conditions face stressors related to their condition in addition to those typical of childhood and adolescence, placing them at risk of high allostatic load. The purpose of this secondary analysis was to examine whether youth with chronic health conditions differ from controls on clinical measures of allostatic load. Design and methodsA secondary analysis of two datasets, the electronic health record of a tertiary children's hospital and data from the Survey of the Health of Wisconsin, compared youth with chronic health conditions to controls on clinical measures of allostatic load. Additional analyses explored whether parental stress and mental health influenced these relationships. ResultsAnalyses identified differences in BMI, blood pressure, and waist circumference between youth with food allergy, anxiety, or depression, and controls. These relationships differed for males and females and for those with comorbid mental and physical conditions, and were influenced by parent stress and mental health. ConclusionsResults support future studies exploring whether high stress in youth with chronic health conditions leads to increased allostatic load. Incorporating biomarkers as well as genetic and epigenetic factors will provide critical insights. Practice implicationsYouth with mental and physical CHCs may be at increased risk of high allostatic load, reflected in clinical measures of metabolism, and should have regular assessments of their metabolic health.

Social isolation in adolescence and long-term changes in the gut microbiota composition and in the hippocampal inflammation: Implications for psychiatric disorders – Dirk Hellhammer Award Paper 2021

Exposure to early adverse experiences induces persistent changes in physiological, emotional and behavioural functions predisposing the individual to an enhanced vulnerability to develop different disorders during lifespan. The adverse outcomes depend upon the timing of the stressful experiences, and in this contest, adolescence represents a key sensitive period for brain development. Among the biological systems involved, gut microbiota has recently been proposed to act on the interplay between the stress response, brain functions and immune system, through the gut-brain axis communication.In the current study we aimed to evaluate, in a preclinical model, changes over time in the microbiota community structure in physiological condition and in response to stress during adolescence. We also aimed to correlate the microbiota composition to the inflammatory status in brain.We used the preclinical model of social deprivation in rats during adolescence, based on the lack of all social contacts, for four weeks after weaning, followed by re-socialization until adulthood. We collected fecal samples at different post-natal days to investigate the short- and long-lasting effects of social isolation on gut microbiota composition and we collected brain areas (dorsal and ventral hippocampus) samples at killing to measure a panel of inflammatory and microglia activation markers.16 S metataxonomic sequencing analysis revealed that microbial changes were influenced by age in both isolated and controls rats, regardless of sex, whereas social isolation impacted the microbial composition in a sex-dependent manner. A multivariate analysis showed that social isolation induced short-term gut microbiota alterations in females but not in males. We also identified several stress-related genera associated with social isolation condition. In brain areas we found a specific inflammatory pattern, in dorsal and ventral hippocampus, that significantly correlated with gut microbiota composition.Overall, in this study we reported a novel sex-specific association between gut microbiota composition and inflammatory response related to social isolation paradigm during adolescence, suggesting that stressful experiences during this sensitive period could have a long-lasting impact on the development of different biological systems that could in turn influence the vulnerability to develop mental disorders later in life.

Chirality and asymmetry increase the potency of candidate ADRM1/RPN13 inhibitors.

Bortezomib and the other licensed 20S proteasome inhibitors show robust activity against liquid tumors like multiple myeloma, but have disappointed against solid tumors including ovarian cancer. Consequently, interest is mounting in alternative non-peptide based drugs targeting the proteasome’s 19S regulatory particle subunit, including its ubiquitin receptor RPN13. RA183 and RA375 are more potent analogs of the prototypic inhibitor of RPN13 (iRPN13) called RA190, and they show promise for the treatment of ovarian cancer. Here we demonstrate that rendering these candidate RPN13 inhibitors chiral and asymmetric through the addition of a single methyl to the core piperidone moiety increases their potency against cancer cell lines, with the S-isomer being more active than the R-isomer. The enhanced cancer cell cytotoxicities of these compounds are associated with improved binding to RPN13 in cell lysates, ATP depletion by inhibition of glycolysis and mitochondrial electron chain transport, mitochondrial depolarization and perinuclear clustering, oxidative stress and glutathione depletion, and rapid accumulation of high molecular weight polyubiquitinated proteins with a consequent unresolved ubiquitin proteasome system (UPS) stress response. Cytotoxicity was associated with an early biomarker of apoptosis, increased surface annexin V binding. As for cisplatin, BRCA2 and ATM deficiency conferred increased sensitivity to these iRPN13s. Ubiquitination plays an important role in coordinating DNA damage repair and the iRPN13s may compromise this process by depletion of monomeric ubiquitin following its sequestration in high molecular weight polyubiquitinated protein aggregates. Indeed, a synergistic cytotoxic response was evident upon treatment of several ovarian cancer cell lines with either cisplatin or doxorubicin and our new candidate iRPN13s, suggesting that such a combination approach warrants further exploration for the treatment of ovarian cancer.

Future-Proofing Startups: Stress Management Principles Based on Adaptive Calibration Model and Active Inference Theory.

In this paper, the Adaptive Calibration Model (ACM) and Active Inference Theory (AIT) are related to future-proofing startups. ACM encompasses the allocation of energy by the stress response system to alternative options for action, depending upon individuals’ life histories and changing external contexts. More broadly, within AIT, it is posited that humans survive by taking action to align their internal generative models with sensory inputs from external states. The first contribution of the paper is to address the need for future-proofing methods for startups by providing eight stress management principles based on ACM and AIT. Future-proofing methods are needed because, typically, nine out of ten startups do not survive. A second contribution is to relate ACM and AIT to startup life cycle stages. The third contribution is to provide practical examples that show the broader relevance ACM and AIT to organizational practice. These contributions go beyond previous literature concerned with entrepreneurial stress and organizational stress. In particular, rather than focusing on particular stressors, this paper is focused on the recalibrating/updating of startups’ stress responsivity patterns in relation to changes in the internal state of the startup and/or changes in the external state. Overall, the paper makes a contribution to relating physics of life constructs concerned with energy, action and ecological fitness to human organizations.

Stress system response divergence revealed by integrating reactivity of stress pathways to psychological stress in lean and overweight/obese men

While sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis responses to psychological stress are important in their own accord, the overall response involves integrated reactivity of both pathways. The integrated response was hypothesised to reveal differences not evident in either system alone Age matched lean (n=19) and overweight/obese (n=17) men were subjected to a Trier Social Stress Test and SAM system (SBP, DBP) and HPA axis (salivary cortisol) reactivity measured. Integrated reactivity of SAM and HPA pathways was calculated using ratios. Considering HPA axis relative to SAM system (i.e., HPA/SAM ratio) revealed significantly lower cortisol over SBP (CoSBP; time*condition: F[14, 476]=1.970, p=0.018) and cortisol over DBP (CoDBP; time*condition: F[14, 476]=1.924, p=0.022) reactivity in overweight/obese compared with lean men. Measures of SAM/HPA reactivity were unaltered. Cortisol response per unit of blood pressure response was blunted in men with elevated adiposity. These findings support there being a coordinated overall approach to stress pathway reactivity with the degree of activation in one pathway related to the degree of activation of the other.

Stress impairs response to antidepressants by activating HPA axis and immune system

While early adverse events as well as severe stressful events occurring later in life have been associated with depression, the interaction is still not understood. The objective of this study is to disentangle the interaction by evaluating the main stress-response systems of the body, the hypothalamic-pituitary-adrenal (HPA-) axis and the immune system in depressed patients. HPA-axis function was evaluated by analyzing FKBP5, SGK1 and NR3C1 mRNA-expression in whole blood after an in vivo glucocorticoid receptor challenge with 1.5 mg dexamethasone in 150 depressed in-patients. Early adverse events were evaluated using the Childhood Trauma Questionnaire (CTQ), severe life events occurring one year prior to hospital admission were assessed with the List of Threatening Experiences (LTE). History of 3 and more severe life events was associated with a significantly impaired treatment response to antidepressants. Additionally, there was a significant association with an impaired GR-induction of SGK1 and FKBP5 mRNA expression, as well as with increased measures of the immune system such as lymphocyte count and CRP. These alterations were not observable in relation to early adverse effects. Severe life events that happen prior to the development of depression significantly impair the HPA-axis and the response to antidepressants. Therefore patients who report stressful life events should receive additional treatment options such as psychotherapy already at the beginning of therapy.

Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.

The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen Serratia marcescens was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation. The Rcs system is activated by a variety of insults, including β-lactam antibiotics and polymyxin B. In this study, we developed three luminescence-based transcriptional reporters for Rcs system activity and used them to test whether antibiotics used for empiric treatment of ocular infections influence Rcs system activity in a keratitis isolate of S. marcescens. These included antibiotics to which the bacteria were susceptible and resistant. Results indicate that cefazolin, ceftazidime, polymyxin B, and vancomycin activate the Rcs system to varying degrees in an RcsB-dependent manner, whereas ciprofloxacin and tobramycin activated the promoter fusions, but in an Rcs-independent manner. Although minimum inhibitory concentration (MIC) analysis demonstrated resistance of the test bacteria to polymyxin B and vancomycin, the Rcs system was activated by sub-inhibitory concentrations of these antibiotics. Together, these data indicate that a bacterial stress system that influences numerous pathogenic phenotypes and drug-tolerance is influenced by different classes of antibiotics despite the susceptibility status of the bacterium.

The Pubertal Stress Recalibration Hypothesis: Potential Neural and Behavioral Consequences.

Recent research has suggested that the pubertal period provides an opportunity for recalibrating the stress-responsive systems in youth whose responses to stress have been altered by early adversity. Such recalibration may have cascading effects that affect brain and behavioral development. In this article, we consider a large, cross-species literature to demonstrate the potential importance of pubertal stress recalibration for understanding the development of psychopathology following early deprivation by caregivers. We review the evidence for recalibration of the hypothalamic-pituitary-adrenal axis in humans, examine research on rodents that has established mechanisms through which stress hormones affect brain structure and function, and summarize the literature on human neuroimaging to assess how these mechanisms may translate into changes in human behavior. Finally, we suggest ideas for elucidating the consequences of pubertal stress recalibration that will improve our understanding of adaptive and maladaptive adolescent behavior following early adversity.

Air pollution and environmental health disparities: how disadvantaged communities may be particularly susceptible to poor reproductive outcomes

BACKGROUND AND AIM: Disadvantage communities face differential exposure to high levels of air pollution and other environmental hazards. In addition to having fewer resources and several co-occurring risk factors such as increased psychosocial stress, fewer opportunities for health promoting behaviors and less access to high quality health care, they also have less access to protective factors. These factors drive differential susceptibility across population subgroups and can explain why disadvantaged populations suffer disproportionately from the negative health effects of air pollution. The aim of this presentation is to describe different models that frame differential exposure and susceptibility and provide evidence to support these phenomenon specifically among pregnant people and those who may become pregnant. METHODS: I will present three frameworks/conceptual models that are rooted in theory and capture the way social and environmental factors interact to produce environmental health disparities. RESULTS:The social production of disease model, the integrated social-environmental model of health and well-being, and the stress-exposure-disease model will be discussed. I will highlight the important contributions of each. Shared mechanistic pathways such as those involved with the stress response system (i.e., allostatic load), the inflammatory and sympathathic nervous systems will be emphasized. Lastly, I will present empirical evidence to support the theorized mechanisms and upstream social and contextual factors that contribute to environmental health disparities, with a specific emphasis on race and socioeconomic status, in reproductive health. CONCLUSIONS:The use of conceptual frameworks rooted in theory can strengthen environmental health disparities research. KEYWORDS: air pollution, environmental health disparities, conceptual models, reproductive health

Progress on the function and regulatory mechanisms of bacterial Cpx signal transduction system

The Cpx (conjugative pilus expression) two-component signal transduction system is a complex envelope stress response system in Gram-negative bacteria, which can sense a variety of extracellular stimuli that enter the signaling pathway at different points. The phosphorylation of the CpxR, the cytoplasmic cognate response regulator of the Cpx system, can lead to changes in the expression of genes encoding proteins involved in inner and outer membrane functions. Activation of the Cpx system contributes to bacterial resistance/tolerance to certain antibiotics and acidic stress. In this review, we summarize the composition, and the mechanisms of signal detection, and the transcriptional regulation of the Cpx system, with a goal to provide guidance for the study of the regulatory network of the Cpx system and its important regulatory roles in bacterial physiology.

Multi-Transcript Level Profiling Revealed Distinct mRNA, miRNA, and tRNA-Derived Fragment Bio-Signatures for Coping Behavior Linked Haplotypes in HPA Axis and Limbic System.

The molecular basis of porcine coping behavior (CB) relies on a sophisticated interplay of genetic and epigenetic features. Deep sequencing technologies allowed the identification of a plethora of new regulatory small non-coding RNA (sncRNA). We characterized mRNA and sncRNA profiles of central parts of the physiological stress response system including amygdala, hippocampus, hypothalamus and adrenal gland using systems biology for integration. Therefore, ten each of high- (HR) and low- (LR) reactive pigs (n = 20) carrying a CB associated haplotype in a prominent QTL-region on SSC12 were selected for mRNA and sncRNA expression profiling. The molecular markers related to the LR group included ATP1B2, MPDU1, miR-19b-5p, let-7g-5p, and 5′-tiRNALeu in the adrenal gland, miR-194a-5p, miR-125a-5p, miR-7-1-5p, and miR-107-5p in the hippocampus and CBL and PVRL1 in the hypothalamus. Interestingly, amygdalae of the LR group showed 5′-tiRNA and 5′-tRF (5′-tRFLys, 5′-tiRNALys, 5′-tiRNACys, and 5′-tiRNAGln) enrichment. Contrarily, molecular markers associated with the HR group encompassed miR-26b-5p, tRNAArg, tRNAGlyiF in the adrenal gland, IGF1 and APOD in the amygdala and PBX1, TOB1, and C18orf1 in the hippocampus and miR-24 in the hypothalamus. In addition, hypothalami of the HR group were characterized by 3′-tiRNA enrichment (3′-tiRNAGln, 3′-tiRNAAsn, 3′-tiRNAVal, 3′-tRFPro, 3′-tiRNACys, and 3′-tiRNAAla) and 3′-tRFs enrichment (3′-tRFAsn, 3′-tRFGlu, and 3′-tRFVal). These evidence suggest that tRNA-derived fragments and their cleavage activity are a specific marker for coping behavior. Data integration revealed new bio-signatures of important molecular interactions on a multi-transcript level in HPA axis and limbic system of pigs carrying a CB-associated haplotype.

A proteomic analysis of the effect of ocean acidification on the haemocyte proteome of the South African abalone Haliotis midae

As a result of increasing CO2 emissions and the prevalence of global climate change, ocean acidification (OA) is becoming more pervasive, affecting many trophic levels, particularly those that rely on succinctly balanced ocean chemistry. This ultimately threatens community structures, as well as the future sustainability of the fishing/aquaculture industry. Understanding the molecular stress response of key organisms will aid in predicting their future survivability under changing environmental conditions. This study sought to elucidate the molecular stress response of the South African abalone, Haliotis midae, an understudied organism with high economic value, utilising a high throughput iTRAQ-based proteomics methodology. Adult abalone were exposed to control (pH 7.9) and experimental (pH 7.5) conditions for 12, 72 and 168 h, following which protein was isolated from sampled haemocytes and subsequently processed. iTRAQ-labelled peptides were analysed using mass spectrometry, while an array of bioinformatics tools was utilised for analysing the proteomic data. COG analysis identified “Cytoskeleton”, “Translation, ribosomal structure and biogenesis”, “Post-translational modification, protein turnover, chaperones”, and “Intracellular trafficking, secretion and vesicular transport” to be the most enriched functional classes, while statistical analysis identified a total of 33 up-regulated and 23 down-regulated effectors of OA stress in abalone. Several of the up-regulated proteins that were identified function in central metabolism (ENO1, PGK, DUOX1, GPD2), the stress/immune response (CAMKI, HSPA5/GRP78, MAPKI), and cytoskeleton, protein sorting and signal transduction (IQGAP1, MYO9B, TLN1, RDX, TCP-1/CCT, SNX6, CHMP1a, VPS13a). Protein-protein interactions were predicted using STRING DB, Cytoscape and Ingenuity Pathway Analysis, providing a model of the effects of OA on the H. midae haemocyte proteome. The data indicated that H. midae underwent a metabolic shift under OA conditions to utilize more energy-efficient mechanisms of ATP generation, while attempts at restoring haemocyte stabilisation and homeostasis were reflected by up-regulation of oxidative stress and cytoskeletal proteins. Our results support other molluscan studies that report a complex array of overlapping functions of both the stress and immune response systems. This interplay of the mounted stress and immune response is maintained and observed through the up-regulation of proteins involved in protein synthesis and turnover, as well as intracellular signalling and transport. The data presented in this study highlight the value of employing sensitive and robust -omics technologies for assessing the effects of changing environmental conditions on marine organisms.

Associations between Consistent and High-quality Teacher-child Interactions and Preschool Children’s Self-regulation and Activity in the Stress Response System

ABSTRACT Research Findings: This study aims to understand the ways in which classroom-level teacher-child interaction quality is predictive of self-regulatory behavior and physiology. Specifically, we examine if high-quality and consistent behavioral and emotional support are related to preschool children’s behavioral self-regulation, inhibitory control, and morning cortisol levels at child care. Fifty-four children within 11 center-based preschool classrooms participated. Saliva was collected at child care over two mornings and assayed for cortisol; two direct assessments of self-regulation were conducted. Classroom quality was observed over two days with the Classroom Assessment Scoring System. Models predicting self-regulation find that high-quality Emotional Support predicted higher behavioral self-regulation and inhibitory control skills for preschool children. No significant associations with consistency of teacher-child interactions emerged; however, there was a trend-level association between consistently managed classrooms and behavioral self-regulation. Results indicate no association between classroom-level interaction quality or consistency and children’s cortisol at child care. Practice or Policy: Our findings indicate that classroom-level, emotionally supportive interactions predict higher behavioral self-regulation and inhibitory control for preschool children. Thus, teachers who foster relationships in the classroom that are supportive and responsive may help to support preschool children’s self-regulation skills.