Gene network and proteomic analyses of cardiac responses to pathological and physiological stress

Background—The molecular mechanisms underlying similarities and differences between physiological and pathological left ventricular hypertrophy (LVH) are of intense interest. Most previous work involved targeted analysis of individual signaling pathways or screening of transcriptomic profiles. We developed a network biology approach using genomic and proteomic data to study the molecular patterns that distinguish pathological and physiological LVH. Methods and Results—A network-based analysis using graph theory methods was undertaken on 127 genome-wide expression arrays of in vivo murine LVH. This revealed phenotype-specific pathological and physiological gene coexpression networks. Despite >1650 common genes in the 2 networks, network structure is significantly different. This is largely because of rewiring of genes that are differentially coexpressed in the 2 networks; this novel concept of differential wiring was further validated experimentally. Functional analysis of the rewired network revealed several distinct cellular pathways and gene sets. Deeper exploration was undertaken by targeted proteomic analysis of mitochondrial, myofilament, and extracellular subproteomes in pathological LVH. A notable finding was that mRNA–protein correlation was greater at the cellular pathway level than for individual loci. Conclusions—This first combined gene network and proteomic analysis of LVH reveals novel insights into the integrated pathomechanisms that distinguish pathological versus physiological phenotypes. In particular, we identify differential gene wiring as a major distinguishing feature of these phenotypes. This approach provides a platform for the investigation of potentially novel pathways in LVH and offers a freely accessible protocol (http://sites.google.com/site/cardionetworks) for similar analyses in other cardiovascular diseases.

Electric shock causes physiological stress responses in shore crabs, consistent with prediction of pain

Animal pain is defined by a series of expectations or criteria, one of which is that there should be a physiological stress response associated with noxious stimuli. While crustacean stress responses have been demonstrated they are typically preceded by escape behaviour and thus the physiological change might be attributed to the behaviour rather than a pain experience. We found higher levels of stress as measured by lactate in shore crabs exposed to brief electric shock than non-shocked controls. However, shocked crabs showed more vigorous behaviour than controls. We then matched crabs with the same level of behaviour and still found that shocked crabs had stronger stress response compared with controls. The finding of the stress response, coupled with previous findings of long-Term motivational change and avoidance learning, fulfils the criteria expected of a pain experience.

Physiological stress responses in the warm-water fish matrinxã (Brycon amazonicus) subjected to a sudden cold shock.

Respostas fisiológicas ao estresse do peixe de águas tépidas matrinxã (Brycon amazonicus) submetido à queda brusca de temperatura.

Biological markers of stress in pediatric acute burn injury

BACKGROUND Burns and their associated wound care procedures evoke significant stress and anxiety, particularly for children. Little is known about the body's physiological stress reactions throughout the stages of re-epithelialization following an acute burn injury. Previously, serum and urinary cortisol have been used to measure stress in burn patients, however these measures are not suitable for a pediatric burn outpatient setting. AIM To assess the sensitivity of salivary cortisol and sAA in detecting stress during acute burn wound care procedures and to investigate the body's physiological stress reactions throughout burn re-epithelialization. METHODS Seventy-seven participants aged four to thirteen years who presented with an acute burn injury to the burn center at the Royal Children's Hospital, Brisbane, Australia, were recruited between August 2011 and August 2012. RESULTS Both biomarkers were responsive to the stress of burn wound care procedures. sAA levels were on average 50.2U/ml higher (p<0.001) at 10min post-dressing removal compared to baseline levels. Salivary cortisol levels showed a blunted effect with average levels at ten minutes post dressing removal decreasing by 0.54nmol/L (p<0.001) compared to baseline levels. sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child Trauma Screening Questionnaire scores at three months post re-epithelialization (p=0.008). Similarly, salivary cortisol was associated with no medication (p<0.001), pain scores (p=0.045) and total body surface area of the burn (p=0.010). CONCLUSION Factors which support the use of sAA over salivary cortisol to assess stress during morning acute burn wound care procedures include; sensitivity, morning clinic times relative to cortisol's diurnal peaks, and relative cost.

Barley genotype expressing "stay-green"-like characteristics maintains starch quality of the grain during water stress condition

The identification of "stay-green" in sorghum and its positive correlation with yield increases has encouraged attempts to incorporate "stay-green"-like traits into the genomes of other commercially important cereal crops. However, knowledge on the effects of "stay-green" expression on grain quality under extreme physiological stress is limited. This study examines impacts of "stay-green"-like expression on starch biosynthesis in barley (Hordeum vulgare L.) grain under mild, severe, and acute water stress conditions induced at anthesis. The proportions of long amylopectin branches and amylose branches in the grain of Flagship (a cultivar without "stay-green"-like characteristics) were higher at low water stress, suggesting that water stress affects starch biosynthesis in grain, probably due to early termination of grain fill. The changes in long branches can affect starch properties, such as the rates of enzymatic degradation, and hence its nutritional value. By contrast, grain from the "stay-green"-like cultivar (ND24260) did not show variation in starch molecular structure under the different water stress levels. The results indicate that the cultivar with "stay-green"-like traits has a greater potential to maintain starch biosynthesis and quality in grain during drought conditions, making the "stay-green"-like traits potentially useful in ensuring food security. (C) 2013 Elsevier Ltd. All rights reserved.

Carbon and nitrogen metabolism of an eutrophication tolerative macrophyte, Potamogeton crispus, under NH4+ stress and low light availability

Submersed macrophytes in eutrophic lakes often experience high NH4+ concentration and low light availability in the water column. This study found that an NH4+-N concentration of 1 mgL(-1) in the water column apparently caused physiological stress on the macrophyte Potamogeton crispus; L The plants accumulated free amino acids (FAA) and lost soluble carbohydrates (SC) under NH4+ stress. These stressful effects of NH4+ were exacerbated under low light availability. Shading significantly increased NH4+ and FAA contents and dramatically decreased SC and starch contents in the plant shoots. At an NH4+-N concentration of 1 mg L-1 in the water column, neither growth inhibition nor NH4+ accumulation was observed in the plant tissues of P. crispus under normal light availability. The results showed that 1 mg L-1 NH4+-N in the water column was not toxic to P. crispus in a short term. To avoid NH4+ toxicity. active NH4+ transportation out of the cell may cost energy and thus result in a decline of carbohydrate. When NH4+ inescapably accumulates in the plant cell, i.e. under NH4+ Stress and shading, NH4+ is scavenged by FAA synthesis. (c) 2009 Published by Elsevier B.V.

Variation in elemental stoichiometry of the marine diatomThalassiosira weissflogii(Bacillariophyceae) in response to combined nutrient stress and changes in carbonate chemistry

The combined consequences of the multi-stressors of pH and nutrient availability upon the growth of a marine diatom were investigated. Thalassiosira weissflogii was grown in N- or P-limited batch culture in sealed systems, with pH commencing at 8.2 (extant conditions) or 7.6 (ocean acidification [OA] conditions), and then pH was allowed to either drift with growth, or was held fixed. Results indicated that within the pH range tested, the stability of environmental pH rather than its value (i.e., OA vs. extant) fundamentally influenced biomass accumul-ation and C:N:P stoichiometry. Despite large changes in total alkalinity in the fixed pH systems, final biomass production was consistently greater in these systems than that in drifting pH systems. In drift systems, pH increased to exceed pH 9.5, a level of alkalinity that was inhibitory to growth. No statis-tically significant differences between pH treatments were measured for N:C, P:C or N:P ratios during nutrient-replete growth, although the diatom expre-ssed greater plasticity in P:C and N:P ratios than in N:C during this growth phase. During nutrient-deplete conditions, the capacity for uncoupled carbon fixa-tion at fixed pH was considerably greater than that measured in drift pH systems, leading to strong contrasts in C:N:P stoichiometry between these treatments. Whether environmental pH was stable or drifted directly influenced the extent of physiological stress. In contrast, few distinctions could be drawn between extant versus OA conditions for cell physiology.

Supporting the Supporter: Social Support, Stress, and Well-being among Caregivers of Children with Severe Disabilities

Thesis (Ph.D.)--University of Washington, 2014

Modulation des souvenirs neutres et émotifs consolidés : rôle du stress et des hormones de stress

Il a été suggéré que lorsqu’une trace de mémoire consolidée est rappelée (réactivée), elle devient instable et sujette aux modifications avant de se stabiliser à nouveau en mémoire à long terme. Nous avons récemment démontré que lorsque la réactivation d’un souvenir négatif est couplée à l’exposition à un stress psychosocial, le souvenir de l’évènement négatif est augmenté de façon durable. En se basant sur ces résultats, le but de cette thèse est de préciser le rôle du stress psychologique et physiologique (hormones de stress) sur la modulation de souvenirs réactivés. Plus précisément, la première étude visait à déterminer si le cortisol, hormone de stress majeure, est un joueur clé dans la modulation des souvenirs réactivés. Pour ce faire, nous avons inhibé pharmacologiquement les niveaux de cortisol au moment de la réactivation d’un souvenir contenant des segments neutres et négatifs. Les résultats démontrent que la réactivation du matériel négatif est amoindrie lorsque les niveaux de cortisol sont inhibés, et cet effet est toujours présent quatre jours plus tard. Étant donné que les stimuli utilisés jusqu’à maintenant ont une faible validité écologique, nous avons voulu déterminer si d’autres types de mémoires pouvaient également être modulables lors de leur réactivation. L’objectif de la deuxième étude était donc de déterminer si les mémoires autobiographiques collectives sont modulables par le stress au moment de leur réactivation. Pour ce faire, nous avons exposé les participants à de vrais extraits de journaux, neutres ou négatifs, afin de réactiver les mémoires collectives associées à ces évènements. Par la suite, tous les participants ont été exposés à un stress psychosocial et leur mémoire des extraits a été évaluée la journée suivante. Les résultats démontrent que les femmes ayant lu les nouvelles négatives avaient une réactivité physiologique accrue face au stresseur et une mémoire augmentée de ces mêmes nouvelles le jour suivant. Ce phénomène n’était cependant pas observable chez les hommes. Le but de la troisième étude était de déterminer si les mémoires autobiographiques personnelles sont modulables par le stress au moment de leur réactivation. Nous avons demandé aux participants de se remémorer deux évènements de leur passé, négatifs ou neutres. Par la suite, ils ont été exposés à un stress psychosocial et leur mémoire pour ces mêmes évènements a été évaluée à nouveau la journée suivante. Les résultats démontrent que les mémoires autobiographiques personnelles réactivées ne semblent pas être modulables par l’exposition à un stresseur. Globalement, les résultats de cette thèse démontrent que le cortisol a la capacité de moduler des souvenirs négatifs réactivés, mais que la nature (extrinsèque vs. intrinsèque) et l'intensité des souvenirs réactivés sont des facteurs déterminants pour que ce phénomène prenne place.

La stabilité des réponses physiologiques face au stress psychologique telle qu’étudiée sur une période de trois ans

Le stress augmente le risque de développer des maladies cardiovasculaires (CV) ainsi que de mourir de ces maladies. Selon certaines hypothèses, ce phénomène se produirait par le biais de réponses répétés de réactivité physiologique élevée ou de récupération physiologique prolongée, suite à un épisode de stress. La stabilité à long terme des réponses physiologiques face au stress a reçu peu d’attention. Objectifs: (1) Évaluer la stabilité temporelle de la réactivité et de la récupération physiologique suite au stress, à travers l’évaluation des systèmes cardiovasculaires et nerveux autonome, et ce sur un intervalle de 3 ans. (2) Déterminer si le sexe et l'âge agissent comme des variables modératrices. Méthodologie: Un total de 134 hommes et femmes en santé ont été recrutés au sein de la communauté et ont pris part à 2 séances en laboratoire. Quatre tâches, d’une durée de 5 minutes chacune et composée d’un élément de stress interpersonnel différent, ont été administrées. Chaque tâche était suivie d’une période de récupération de 5 min. Des mesures de la fréquence cardiaque (FC), de la pression artérielle (PA) et de la variabilité de la fréquence cardiaque (VFC : HF, LF et VLF) ont été obtenues. Des corrélations de Spearman et des régressions linéaires ont été effectuées. Résultats: Des corrélations test-retest significatives ont été obtenues pour toutes les mesures physiologiques, sauf pour la PA diastolique et la VLF, lors de la période de récupération. Aucune différence significative quant à la stabilité des réponses face au stress en fonction du sexe ou de l’âge des participants, n’a été trouvée. Conclusion: Les réponses physiologiques face au stress représentent des caractéristiques individuelles stables sur trois ans, peu affectées par le sexe et l’âge.

Association entre l'utilisation de Facebook et les marqueurs de stress psychologiques et physiologiques chez les adolescents

La création de Facebook est venue changer la façon dont les gens interagissent, mais nous en savons peu sur les impacts de Facebook sur la santé et le bien-être. À l’heure actuelle, environ 90 % des adolescents sont actifs sur Facebook et la majorité l’utilise tous les jours. Sachant que l’adolescence est une période critique du développement et que lors de cette période les adolescents sont particulièrement vulnérables aux effets du stress, il importe de comprendre les facteurs pouvant entrainer une augmentation des hormones de stress chez les adolescents. Le but du présent mémoire était donc d’étudier la relation entre l’utilisation de Facebook chez les adolescents et des marqueurs de stress psychologique et physiologique. Pour ce faire, nous avons mesuré les hormones de stress chez 88 adolescents (41 garçons, 47 filles) âgés entre 12 et 17 ans. Les adolescents devaient remplir le ‘Social Network Survey’, un questionnaire mesurant différents facteurs associés à l’utilisation de Facebook et le ‘Child Depression Inventory’, qui mesure les symptômes de dépression. Les résultats suggèrent que ce n’est pas le temps passé sur Facebook qui est en lien avec le stress psychologique et physiologique, mais plutôt la nature de l’utilisation de Facebook. Pour les filles, c’est le nombre d’amis sur Facebook qui est relié à des hauts niveaux de cortisol, tandis que pour les garçons c’est le fait de s’exposer sur Facebook. Cette étude est la première à démontrer une association entre la nature de l’utilisation de Facebook et les niveaux d’hormones de stress chez des adolescents.

Exercise and Training at Altitudes: Physiological Effects and Protocols

An increase in altitude leads to a proportional fall in the barometric pressure, and a decrease in atmospheric oxygen pressure, producing hypobaric hypoxia that affects, in different degrees, all body organs, systems and functions. The chronically reduced partial pressure of oxygen causes that individuals adapt and adjust to physiological stress. These adaptations are modulated by many factors, including the degree of hypoxia related to altitude, time of exposure, exercise intensity and individual conditions. It has been established that exposure to high altitude is an environmental stressor that elicits a response that contributes to many adjustments and adaptations that influence exercise capacity and endurance performance. These adaptations include in crease in hemoglobin concentration, ventilation, capillary density and tissue myoglobin concentration. However, a negative effect in strength and power is related to a decrease in muscle fiber size and body mass due to the decrease in the training intensity. Many researches aim at establishing how training or living at high altitudes affects performance in athletes. Training methods, such as living in high altitudes training low, and training high-living in low altitudes have been used to research the changes in the physical condition in athletes and how the physiological adaptations to hypoxia can enhanceperformance at sea level. This review analyzes the literature related to altitude training focused on how physiological adaptations to hypoxic environments influence performance, and which protocols are most frequently used to train in high altitudes.

Dual-specificity phosphatases in the hypo-osmotic stress response of keratin-defective epithelial cell lines

Although mutations in intermediate filament proteins cause many human disorders, the detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. In this study, selected keratin mutations were analysed for their effect on the epidermal stress response. Expression profiles of two keratin-mutant cell lines from epidermolysis bullosa simplex patients (one severe and one mild) were compared to a control keratinocyte line before and after challenge with hypo-osmotic shock, a common physiological stress that transiently distorts cell shape. Fewer changes in gene expression were found in cells with the severely disruptive mutation (55 genes altered) than with the mild mutation (174 genes) or the wild type cells (261 genes) possibly due to stress response pre-activation in these cells. We identified 16 immediate-early genes contributing to a general cell response to hypo-osmotic shock, and 20 genes with an altered expression pattern in the mutant keratin lines only. A number of dual-specificity phosphatases (MKP-1, MKP-2, MKP-3, MKP-5 and hVH3) are differentially regulated in these cells, and their downstream targets p-ERK and p-p38 are significantly up-regulated in the mutant keratin lines. Our findings strengthen the case for the expression of mutant keratin proteins inducing physiological stress, and this intrinsic stress may affect the cell responses to secondary stresses in patients' skin.

Sex differences in reward-related decision processing under stress

Recent research indicates gender differences in the impact of stress on decision behavior, but little is known about the brain mechanisms involved in these gender-specific stress effects. The current study used functional magnetic resonance imaging (fMRI) to determine whether induced stress resulted in gender-specific patterns of brain activation during a decision task involving monetary reward. Specifically, we manipulated physiological stress levels using a cold pressor task, prior to a risky decision making task. Healthy men (n = 24, 12 stressed) and women (n = 23, 11 stressed) completed the decision task after either cold pressor stress or a control task during the period of cortisol response to the cold pressor. Gender differences in behavior were present in stressed participants but not controls, such that stress led to greater reward collection and faster decision speed in males but less reward collection and slower decision speed in females. A gender-by-stress interaction was observed for the dorsal striatum and anterior insula. With cold stress, activation in these regions was increased in males but decreased in females. The findings of this study indicate that the impact of stress on reward-related decision processing differs depending on gender.

Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)