High Levels Of Stress Hormones Research Articles

How stressful is firm insolvency? Self-reported, biological, and physiological indicators of entrepreneurs’ well-being

This study advances research on the nexus of business insolvency and entrepreneurs’ well-being. We broadly build upon the Conservation of Resources Theory (COR) and explore the severity of the impact of firm insolvency on subjective well-being, stress hormones, and physiological recovery. To test our hypotheses, we compared entrepreneurs operating in 51 businesses affected by insolvency with 51 entrepreneurs in a control group. We conducted our study in Germany, where legal regulations surrounding insolvency are relatively unfavorable for those affected. Our findings indicate that entrepreneurs facing insolvency experience lower psychological well-being, greater vital exhaustion, higher stress hormone levels, and, as revealed by supplementary analyses, poorer risk adjustment. Our study complemented entrepreneurs’ self-reports with objective methods to examine entrepreneurial well-being in times of hardship from three perspectives: psychological, biological, and physiological. Although exploratory, our study provides relevant insights into potential repercussions of business failure. JEL CLASSIFICATION: I10; L26; G01

Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours.

Previous studies on paternal epigenetic inheritance have shown that sperm RNAs play a role in this type of inheritance. The microinjection of sperm small noncoding RNAs into fertilised mouse oocytes induces reprogramming of the early embryo, which is thought to be responsible for the differences observed in adult phenotype. While sperm long noncoding RNAs (lncRNAs) have also been investigated in a previous study, their microinjection into fertilised oocytes did not yield conclusive results regarding their role in modulating brain development and adult behavioural phenotypes. Therefore, in the current study we sought to investigate this further. We used our previously established paternal corticosterone (stress hormone) model to assess sperm lncRNA expression using CaptureSeq, a sequencing technique that is more sensitive than the ones used in other studies in the field. Paternal corticosterone exposure led to dysregulation of sperm long noncoding RNA expression, which encompassed lncRNAs, circular RNAs and transposable element transcripts. Although they have limited functional annotation, bioinformatic approaches indicated the potential of these lncRNAs in regulating brain development and function. We then separated and isolated the sperm lncRNAs and performed microinjections into fertilised oocytes, to generate embryos with modulated lncRNA populations. We observed that the resulting adult offspring had lower body weight and altered anxiety and affective behavioural responses, demonstrating roles for lncRNAs in modulating development and brain function. This study provides novel insights into the roles of lncRNAs in epigenetic inheritance, including impacts on brain development and behaviours of relevance to affective disorders.

The role of cortisol and microbiome in the anxiety of people with ASD and the use of ICTs for regulation

The role of hormones and microbiota in individuals with Autism Spectrum Disorder (ASD) has been an area of growing interest and research. Studies have shown that individuals with ASD have differences in their hormonal stress response and gut microbiota compared to typically developing individuals, which may contribute to their difficulties with emotional regulation, social communication, and cognitive flexibility. Research has found that individuals with ASD have higher levels of stress hormones, such as cortisol, which may interfere with mindfulness and attentional control. Additionally, individuals with ASD have been found to have altered gut microbiota, which may contribute to their difficulties with gastrointestinal symptoms and sensory processing. The link between hormones and microbiota in individuals with ASD is complex, and there is evidence to suggest that gut microbiota can influence the stress response and emotional regulation. Furthermore, there is emerging evidence to suggest that interventions targeting the gut microbiota, such as probiotics and prebiotics, may improve some of the behavioral and physiological symptoms associated with ASD. Overall, understanding the complex relationship between hormones and microbiota in individuals with ASD may provide new avenues for developing interventions to improve their overall health and well-being. Further research is needed to fully elucidate these relationships and develop effective interventions to improve the lives of individuals with ASD.

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline.

In recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone. After screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes in vitro and ex vivo, and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and ex vivo experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN, and upregulated the mRNA expression of LAMC2, DSC2, KRT6A, and FOSB, thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects in vivo. Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety in vitro and in vivo. In future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients.

Biobehavioral and psychosocial stress changes during three 8-12month spaceflight analog missions with Mars-like conditions of isolation and confinement.

Prior theories about individual and team adaptation to living and working in an isolated and confined environment (ICE) have been derived from the experiences of individuals who winter-over in Antarctica or deploy for long durations in submarines. These theories are typically described as a 3- to 4-stage process with phases of excitement and elevated alertness, then followed by difficult phases, including depression and volatility. To further evaluate the applicability of these theories to long-duration human spaceflight missions, longitudinal stress responses to prolonged isolation and confinement of three 6-person crews during 8-12months simulated Mars missions were characterized through metabolite profiling (biomarkers in hair and urine samples), wearables monitoring (sleep and activity levels), and self-reported ratings of stress, mood, social participation, and perceived health. These data were normalized, aggregated, and clustered to analyze longitudinal trends in biobehavioral and psychosocial stress measures. As a result, this analysis presents a theoretical model that triangulates aspects of prior theories with new evidence to describe ICE stress at HI-SEAS as 1) eustress of initial adaptation (high stress hormone levels at mission start), 2) deprivation due to prolonged isolation and confinement (decreasing dopamine and serotonin levels), 3) disruption of individual and team dynamics (changes in activity levels, mood, perceived stress, and social participation) and 4) asynchronous coping (changes in sleep-wake cycles, outlook, and team cohesion). These findings support several aspects of prior theories in combination, such as the elevated alertness at mission start and that adverse conditions are most likely to develop after the halfway point of a mission (e.g. for HI-SEAS 8-12months missions, after approximately 6months) followed by a period of volatility until the end (e.g. as stated in Rohrer's theory, ups and downs until the end, not a renewed outlook at the end as described in 3rd quarter phenomenon theory).

Influence of delta-hexachlorocyclohexane (δ-HCH) to Phytophthora ×alni resistant Alnus glutinosa genotypes − Evaluation of physiological parameters and remediation potential

Hexachlorocyclohexanes (HCHs) are persistent organochlorine pesticides with the adverse effects on human health and the environment. The effect of delta-isomer of hexachlorocyclohexane (δ-HCH) on germination, growth parameters and physiological parameters was studied in different Alnus glutinosa (L.) Gaertn. progeny of resistant genotypes to pathogen Phytophthora ×alni. Two experiments were performed: a short-term experiment to determine the effect of δ-HCH on total germination (GT), germination energy (GE), speed of germination (SG), shoot length and biomass of seedlings, and a long-term experiment devoted to remediation aspects. In addition, changes in the hormonal system of alders were monitored in both cases. Significant differences were found between the treated and control group in most of the evaluated characteristics. Also, the content of studied phytohormones differs between groups. Furthermore, the obtained results indicate genetically determined variability in response to δ-HCH. Of the six tested, the Březové and Tuřany progeny seem to be suitable candidates for phytoremediation because of the adaptation to stress conditions or high remediation efficiency. The rest of tested progeny seems to be unsuitable due to higher mortality, lower remediation efficiency and higher levels of stress hormones resulting in significant decrease in biomass and plant height. Moreover, results indicate the role of the plant as a remediation accelerator, probably through released exudates, and a positive effect on the soil microbiome as the presence of plants increased the remediation efficiency by 20.85 – 35.89%. The obtained research findings may be helpful in better understanding the processes involved in removing these pesticides from the soil. Further research should be focused on rhizosphere microbiome, mechanism of in-plant isomerization and metabolites identification.

Occupation and Psychophysiological Status of the Male Population of the Khanty-Mansi Autonomous Area

Introduction: The progressively growing road traffic intensity leads to a steady increase in the informational, emotional and psychological burden in drivers. Truck drivers are exposed to numerous occupational risk factors, including hard labor, constant psychological stress, vibration, noise, a fixed working position, poor visibility, and excess concentrations of noxious gases, all affecting their psychophysiological status. Objective: To study the relationship between professional work and characteristics of the psychophysiological status of the male population of the northern region and to establish the presence and strength of correlations between their elemental and psychoemotional status. Materials and methods: We assessed the psychoemotional status of 182 men aged 32.6 ± 6.2 years, including 94 truck drivers and 88 office workers, living in three northern cities of the Russian Federation. We also established their blood and urinary levels of catecholamines (adrenaline and noradrenaline) using enzyme immunoassay and measured hair magnesium and potassium levels using inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry. Results: We observed that the professional drivers of the northern region were more susceptible to psychological stress (p = 0.042…0.001), had higher levels of stress hormones (cortisol and adrenaline) in blood (p = 0.049…0.005) and urine (p = 0.004…0.003), but lower hair levels of magnesium and potassium, the trace elements essential for mental health (p = 0.004…0.003), than male office workers. The correlation analysis of the above parameters proved that psychological stress of the truck drivers was attributed to magnesium and potassium deficiency (r = -0.475…—0.601) and a high level of stress hormones (r = –0.514…–0.828). Conclusion: In order to stabilize emotional and psychological status and to improve the performance, physical health, and the quality of life of professional drivers, it is important to correct their micronutrient status using multivitamin/multimineral supplements and enriched foods.

Bridging environment, physiology and life history: stress hormones in the Edible Dormouse (Glis glis)

The performance of wild animals is impacted by diverse challenges imposed by the environment and distinct life history stages such as breeding and hibernation. Glucocorticoids (GCs) are hormonal mediators that reflect the response to these challenges, exerting their far-reaching effects on numerous processes such as energy allocation, immunity and behavior. Whereas short term elevations of GC levels are crucial for survival, by activation of the emergency life history stage, chronically increased GCs are capable of impairing various body functions and ultimately hamper survival and reproduction. The aim of this study was to disentangle the effects of reproductive activity, prolonged food limitation and hibernation on stress hormone levels in the Edible Dormouse (Glis glis) and to link them to formerly observed survival rates. We therefore measured urinary cortisol levels in wild Edible Dormice in South-western Germany during their active season (2012-2014). Results of our study revealed that reproductive activity was associated with high cortisol levels. During the mating season, particular individuals with a low body mass had high stress hormone levels. Elevated levels of cortisol were also measured during pre-hibernation fattening and were increased in females that had formerly invested in reproduction. Thus, reproduction represents a demanding, potentially stressful, event for both sexes and is linked to distinctly lowered survival rates occurring during years of high reproductive activity. Prolonged food limitation occurring during years of mast failure, did not affect stress levels and were not associated with increased mortality, demonstrating the ability of dormice to predict and cope with food restriction.

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer's Disease.

Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− and C57BL/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+/− mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.

Bridging environment, physiology and life history: Stress hormones in a small hibernator

Our knowledge of the perception of stress and its implications for animals in the wild is limited, especially in regard to mammals. The aim of this study was therefore to identify sex specific effects of reproductive activity, body mass, food availability and hibernation on stress hormone levels in the edible dormouse (Glis glis), a small mammalian hibernator. Results of our study reveal that reproductive activity and pre-hibernation fattening were associated with high cortisol levels in both sexes. During the mating season, in particular individuals with low body masses had higher stress levels. Elevated levels of cortisol during pre-hibernation fattening were even higher in females that had formerly invested into reproduction compared to non-reproductive females. Previously observed impairments on health parameters and reduced survival rates associated with reproduction emphasize the functional relevance of high stress hormone levels for fitness. Prolonged food limitation, however, did not affect stress levels demonstrating the ability of dormice to predict and cope with food restriction.

Kids’ Outcomes And Long-term Abilities (KOALA): protocol for a prospective, longitudinal cohort study of mild traumatic brain injury in children 6 months to 6 years of age

IntroductionMild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the...

Seabirds as environmental indicators: foraging behaviour and ecophysiology of common diving petrels (Pelecanoides urinatrix) reflect local-scale differences in prey availability

Seabird foraging behaviour can reflect prey abundance at sea, and is influenced by stress hormone levels, thus providing a potential indicator of at-sea conditions. Using common diving petrels (Pelecanoides urinatrix, hereafter CDPs), a procellariform that preferentially forages on crustacean zooplankton, we sought to understand how spatially separate colonies responded behaviourally and physiologically to contrasting prey levels with a view to recruiting this species as an environmental indicator. In 2016, incubating CDPs from Tiritiri Matangi (− 36.59S; 174.88E, low levels of preferred prey) and Burgess (− 35.91S; 174.12E, high levels of preferred prey) Islands within the Hauraki Gulf, New Zealand, were tracked using GPS devices. We hypothesised that Tiritiri birds would exhibit greater foraging effort and higher stress hormone levels across the breeding season due to lower levels of available prey. Hidden Markov methods were used to model foraging effort, and prey trophic level (stable isotopes: δ13C and δ15N) and stress hormone levels (CORT) quantified in plasma samples. During incubation birds were spatially segregated when foraging. Tiritiri birds exerted more effort, chasing higher trophic level prey at larger distances from the colony, and had higher body weight and lower CORT than Burgess birds. However, bird CORT levels responded more to reproductive duties (peaking during chick rearing) as opposed to colony location, i.e. CORT was not consistently higher in Tiritiri birds. Although a snapshot, our findings illustrate the promise of integrating multiple parameters when recruiting seabirds as ocean indicators, resulting in improved resolution of future monitoring programmes based upon them.

Mechanisms of chronic stress influence on the brain hemodynamic in persons with employment-related chronic stress

To discuss the mechanisms by which chronic psychosocial stress (CPSS) affects the parameters of cerebral blood flow. One hundred and sixty locomotive machinists (LM) and machinist assistants (MA), whose profession is rated as one of the most stressful, were enrolled in this study. The control group consisted of 100 healthy volunteers. The activity of the stressor system was assessed by the levels of stress hormones in serum (ACTH, cortisol, adrenaline). The functional state of the endothelium was assessed by secretion of nitric oxide and endothelin-1. Doppler ultrasound was used to measure the linear velocity of blood flow in the cerebral vessels, the size of the intima-media complex of the common carotid artery, and the results of the endothelium-dependent vasodilation. Blood pressure was monitored daily. The action of CPSS is accompanied by the persistent increase in the serum cortisol levels. This process contributes to the development of vasoconstriction with the initiation of endothelial dysfunction with impaired production of nitric oxide and increased secretion of endothelin-1 and the formation of arterial hypertension. With progression of these processes, there is a decrease in cerebral blood flow. The observed increase in the size of the intima-media complex of the common carotid artery correlates with the severity of arterial hypertension and endothelial dysfunction. CPSS leads to a decrease in cerebral blood flow and subsequent development of endothelial dysfunction and arterial hypertension, which are related to high levels of stress hormones circulating in the blood. These processes lead to functional failure of the vascular endothelium.

Biphasic Dose-Response and Hormetic Effects of Stress Hormone Hydrocortisone on Telomerase-Immortalized Human Bone Marrow Stem Cells In Vitro.

Although high levels of stress hormones are associated with well-known negative health outcomes, their low levels can have health-promoting effects by virtue of the phenomenon of mild stress-induced hormesis. We have studied the effects of a wide range (between 100 nmol/L and 150 μmol/L) of hydrocortisone (HC) on human bone marrow stem cells in vitro. Telomerase-immortalized human mesenchymal stem cells (hTERT-MSCs) were exposed to various doses of HC for different durations (1-6 days) and analyzed for survival and metabolic activity by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, for cell migratory ability by a wound-healing assay and for osteoblastic and adipogenic differentiation abilities in vitro. Our findings indicate that hTERT-MSCs exposed to HC resulted in a biphasic hormetic dose–response in some measures but not all. Although the mitochondrial and metabolic MTT activity assay clearly showed low-level stimulatory (between 0.1 and 1 µmol/L) and high-level inhibitory effects (from about 10 µmol/L onward), the cytostatic and differentiation-inducing effects were mostly linear at concentrations between 1 and 100 µmol/L. Further long-term studies will elucidate whether chronic or intermittent exposure of human cells to stress hormones has physiologically beneficial hormetic effects.

Assessing the influence of biotic, abiotic, and social factors on the physiological stress of a large Neotropical primate in Atlantic forest fragments

Wildlife physiological responses to environmental and human-related stressors provide useful clues on animal welfare. Non-invasive biomarkers, such as fecal glucocorticoid metabolites (fGCM), allow researchers to assess whether variations in habitat quality, behavior, and climate influence the animals' physiological stress. We examined the role of fragment size, ambient temperature, ripe fruit availability and consumption, percentage of records moving, sex, female reproductive state, and group composition as predictors of the level of fGCM in adult brown howler monkeys (Alouatta guariba clamitans) inhabiting three small (<10 ha) and three large (>90 ha) Atlantic Forest fragments in southern Brazil. We collected bimonthly behavioral data and fecal samples from adult individuals over three years, and used a multimodel inference framework to identify the main predictors of fGCM. We found that the mean (±SD) fGCM in the study groups ranged from 57 ± 49 ng/g to 93 ± 58 ng/g, which were within the known range for howler monkeys. We found 10 best models including five of the 17 tested variables. Sex and reproductive state were the only variables included in all these models. We found that fGCM was higher in nursing females (mean ± SD = 104 ± 73 ng/g) than in non-nursing females (64 ± 55 ng/g) and males (53 ± 40 ng/g, P < 0.05) and that it decreased with increasing ripe fruit consumption and minimum temperature. However, fragment size did not predict fGCM concentration (groups in small fragments = 71 ± 58 ng/g vs. groups in large fragments = 63 ± 54 ng/g, P > 0.05). We conclude that factors related to the energetic balance of individuals play major roles in modulating the physiological stress of brown howler monkeys. Future studies should investigate the consequences of higher levels of stress hormones on howler monkey health and demography.

Impacts of food-based enrichment on behaviour and physiology of male greater rheas (Rhea Americana, Rheidae, Aves)

Distress can be defined as a biological response of an individual to long-term threats to its homeostasis and it should be avoided from an animal welfare perspective. High levels of stress hormones and the expression of abnormal behaviours are responses normally observed in distressed animals. Captive environments can provoke distress, especially when inappropriate stimuli are provided to the animals. The concomitant use of behavioural and non-invasive hormonal measures is a means to evaluate captive animal welfare. Environmental enrichment is a tool that can reduce distress and minimize the expression of abnormal behaviour in captive animals. The aim of this study was to evaluate greater rheas’ responses (behavioral and hormonal) to food-based enrichment. Three birds from the Belo Horizonte Zoo, Brazil were studied. The study was divided into three phases (baseline, enrichment and post-enrichment): fruits scattered around the birds’ enclosure were used as enrichment. Behaviour and faecal sampling were undertaken in all phases of the study. Abnormal behaviours and faecal glucocorticoid metabolites (GCM) levels showed significant reduction during the environmental enrichment phase, and a significative positive correlation between GCM production and abnormal pacing was observed. From the results of this study, we conclude that the use of food as environmental enrichment should be encouraged because of its positive effects on animal welfare. Besides, studies with larger groups of greater rheas, with individuals of both sexes, should also be encouraged to evaluate if the results found in this pilot study are consistent and can be generalized to the species.

Repeated corticosterone enhances the acquisition and recall of trace fear conditioning

Repeated exposure to high levels of stress hormones can enhance contextual and discrete fear conditioning in rats. A common belief is that this enhanced fear memory is largely mediated by the amygdala because both contextual and discrete fear conditioning are dependent on an intact amygdala. However, trace fear conditioning is thought to be amygdala independent, and therefore, it is not clear what impact stress would have on this form of fear learning. Here, we examined whether the stress hormone corticosterone (CORT) would enhance memory in a hippocampal-dependent trace fear conditioning test. Male Long-Evans rats received either 40mg/kg of CORT or vehicle injections for 21 consecutive days. On day 22, rats received either 1, 2, or 5 tone-trace-shock pairings. On day 23, the rats were tested for behavior to the conditioned tone cues in a novel context. We found that CORT significantly increased the acquisition of trace conditioned fear. We also found that CORT significantly increased recall of trace conditioned cues, but only when a 2 trace-pairing protocol was used during training. These results suggest that CORT can enhance non-amygdala forms of fear learning and memory and that high levels of stress hormones modify the physiological substrates that mediate emotionally driven behavior in tasks that are less dependent on amygdala functioning.

Effects of lions on behaviour and endocrine stress in plains zebras

AbstractLiving under predation risk may alter both behaviour and physiology of potential prey. In extreme cases, such alterations may have serious demographic consequences, and recent studies support that non‐lethal effects of predation may have broad ecological consequences. However, behavioural and physiological responses to predation risk may be related to trade‐offs associated with resource acquisition and direct predation risk. We validated an enzyme‐linked immunoassay (EIA) for non‐invasive monitoring of stress in plains zebras (Equus quagga) from faecal material. We used this assay in combination with behavioural data to assess if plains zebras living with and without lions (Panthera leo) in a mountain savannah in southern Africa differed in behaviour and physiology, and if such differences were influenced by seasons with contrasting resource availability. Zebra group sizes did not differ between areas with and without lions, but zebra groups had more juveniles in an area with lions than groups in an area without lions, but only during the wet season. Similarly, we observed differences in individual vigilance, foraging behaviour and stress hormone concentrations, but all these differences were influenced by seasons. Despite these seasonal influences, our study did not suggest that zebras in an area with lions spent a higher proportion of time being vigilant, a lower proportion of time foraging, or had higher stress hormone levels. Our results instead suggest that zebras' responses to lion presence were highly context dependent and the result of complex interactions between resource abundance and cues about predation risk. Because of the obvious ecological and evolutionary ramifications of such findings, we argue that further research is needed to define the spatial and temporal scales over which predators impose indirect effects on their prey.

Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway

The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1. In addition, we found that not only was M2 molecule expression down-regulated but intracellular ROS generation was also blocked by autophagy induction. In vivo, we observed that mice that received an isoprenaline injection as a stress agent exhibited augmented implanted breast tumor growth, lung metastasis, intratumoral mRNA expression of M2 molecules and serum ROS generation. In contrast, the intratumoral expression of LC3-II and Beclin1 was decreased. In addition, we observed that isoprenaline induced the up-regulation of the intratumoral expression of phosphorylated mTOR, phosphorylated ERK1/2, phosphorylated Tyr705-STAT3 and HIF-1α, whereas rapamycin induced an opposite effect on the same molecules and could abolish the effects of isoprenaline. These results suggest that autophagy might suppress M2 macrophage polarization induced by isoprenaline via the ROS/ERK and mTOR signaling pathway. Our findings provide a theoretical basis for why high levels of stress hormones accelerate the progression of breast cancer, and autophagy may play a role in determining the outcomes of cancer therapy.

Proximal and Distal Predictors of the Spider Monkey's Stress Levels in Fragmented Landscapes.

The rapid loss, fragmentation and degradation of tropical forests threaten the survival of many animal species. However, the way in which these phenomena affect animal health has been poorly explored, thus limiting the design of appropriate conservation strategies. To address this, here we identified using linear mixed models the effect of proximal (diet, activity pattern, hunting and logging) and distal (sum of the basal areas of fruiting-tree species [SBAFS], landscape forest cover and degree of forest fragmentation) variables over fecal glucocorticoid metabolite (fGCM) levels–hormones associated with animal health and fitness–of six groups of spider monkeys (Ateles geoffroyi) inhabiting six landscapes with different spatial structures in Mexico. Proximal variables showed a stronger predictive power over fGCMs than distal. In this sense, increases in travel time, the occurrence of hunting, and reductions in rest time and fruit consumption resulted in higher fGCM levels. Regarding distal variables, increases in SBAFS were negatively related to fGCM levels, thus suggesting that food scarcity increases stress hormone levels. Nevertheless, contrary to theoretical expectations, spider monkeys living in smaller tracts of forest spent less time travelling, but the same time feeding on fruit as those in more forested areas. The lower net energy return associated with this combination of factors would explain why, contrary to theoretical expectations, increased forest cover was associated with increased levels of fGCMs in these groups. Our study shows that, at least in the short term, spider monkeys in fragmented landscapes do not always present higher levels of stress hormones compared to those inhabiting continuous forest, and the importance of preserving fruit sources and controlling hunting for reducing the levels of stress hormones in free ranging spider monkeys.