Oncogene activation leads to cellular transformation by deregulation of biological processes such as proliferation and metabolism. Paradoxically, this can also sensitize cells to nutrient deprivation, potentially representing an Achilles' heel in early stage tumors. The mechanisms underlying this phenotype include loss of energetic and redox homeostasis as a result of metabolic reprogramming, favoring synthesis of macromolecules. Moreover, an emerging mechanism involving the deregulation of mRNA translation elongation through inhibition of eukaryotic elongation factor 2 kinase (eEF2K) is presented. The potential consequences (...) of eEF2K deregulation leading to cell death under nutrient depletion are discussed. Finally, the relevance of eEF2K as a master regulator of the response to nutrient deprivation in vivo, and its potential exploitation for therapeutic targeting of cancers, are elaborated. Overall, a better understanding of the adaptive mechanisms allowing tumors to circumvent oncogene‐induced hypersensitivity to nutrient deprivation is a promising avenue for uncovering novel therapeutic targets in cancers. (shrink)

The integrated stress response (ISR) is a key determinant of tumorigenesis in response to oncogenic forms of stress like genotoxic, proteotoxic and metabolic stress. ISR relies on the phosphorylation of the translation initiation factor eIF2 to promote the translational and transcriptional reprogramming of gene expression in stressed cells. While ISR promotes tumor survival under stress, its hyperactivation above a level of tolerance can also cause tumor death. The tumorigenic function of ISR has been recently demonstrated (...) for lung adenocarcinomas (LUAD) with KRAS mutations. ISR mediates the translational repression of the dual‐specificity phosphatase DUSP6 to stimulate ERK activity and LUAD growth. The significance of this finding is highlighted by the strong anti‐tumor responses of ISR inhibitors in pre‐clinical LUAD models. Elucidation of the mechanisms of ISR action in LUAD progression via cell‐autonomous and immune regulatory mechanisms will provide a better understanding of its tumorigenic role to fully exploit its therapeutic potential in the treatment of a deadly form of cancer. (shrink)

Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine (...) 9 mono‐methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor‐promoting insults is recognized as a significant source of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis. (shrink)

An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival (...) and proliferation, resulting in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival (...) and proliferation, resulting in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Akt, a protein kinase hyperactivated in many tumors, plays a major role in both cell survival and resistance to tumor therapy. A recent study,1 along with other evidences, shows interestingly, that Akt is not a single‐function kinase, but may facilitate rather than inhibit cell death under certain conditions. This hitherto undetected function of Akt is accomplished by its ability to increase reactive oxygen species and to suppress antioxidant enzymes. The ability of Akt to down‐regulate antioxidant defenses uncovers a novel Achilles' (...) heel, which could be exploited by oxidant therapies in order to selectively eradicate tumor cells that express high levels of Akt activity. (shrink)

Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. (...) Dissection of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)

Ultraviolet radiation activates the expression of a wide variety of genes, by pathways which differ between the short non‐solar ultraviolet C (UVC) wavelengths, which are strongly absorbed by nucleic acids, and the long solar ultraviolet A (UVA, 320–380 nm) wavelengths, which generate active oxygen intermediates. Intermediate solar ultraviolet (UV) wavelengths in the UVB (290–320 nm) range also contain an oxidative component, but more closely resemble UVC in their gene activating properties. Short wavelength UV, in common with other extracellular stimuli including (...) growth factors, activates signal transduction events that involve both stress‐ and mitogen‐activated protein kinase cascades. The extrapolation of the complex modulation of gene expression that ensues to the consequences of natural UV exposure requires careful attention to the details of doses and wavelength employed in the model experiments. Nevertheless, there is evidence that UVB irrradiation of skin can activate the expression of proteins including immunomodulating cytokines, ornithine decarboxylase and, to a limited extent, nuclear oncogene products, as well as lead to stabilisation of p53. Non‐cytotoxic doses of UVA radiation also lead to the strong activation of several genes which would be expected to have functional relevance in vivo. (shrink)

The highly structured mechanisms of cancers, their tendency to occur as a response to environmental stress, and the existence of oncogenes, suggest that neoplasticity may represent more than a biological disfunction. It is proposed that cancer exists as a phylogenetic mechanism serving to promote hyperevolution, albeit at the expense of the ontogeny, that is similar to a process recently discovered in bacterial mutations. Cell-surface-associated nucleic acid in tumorigenic cells and sperm cell vectorization of foreign DNA indicate the existence of (...) essential mechanisms necessary to the occurrence of cancer mediated hyperevolution. An analysis of the proposed mechanism indicates that for mutagenesis of chemical cytology, stress induced neoplasticity confers an evolutionary advantage of more than two orders of magnitude. (shrink)

Two different yeasts have a number of genes bearing striking structural and functional homologies to mammalian oncogenes. In yeast these genes are involved in the control of proliferation and early steps in the cell cycle. Many have putative protein kinase activity and some have been shown to control the activity of the enzyme adenylate cyclase which synthesizes cyclic AMP. Mutant forms of these yeast genes have oncogenic activity in mammalian cells.

Proto‐oncogene products may be multi‐functional proteins with various roles in cell differentiation as well as cell proliferation. The molecular biology of the gene products of three well characterized proto‐oncogenes (c‐fos, c‐myc and c‐src) are described, and the roles of three other proto‐oncogene products, involved in hormone and growth factor reception, are reviewed.

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants (...) during stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

The relationships between oncogenes, cell‐cycle control genes, and growth‐related genes are described. An important generalization from the data is that all the oncogenes and cell‐cycle control genes so far characterized appear to be genes for growth factors or for receptors to growth factors, or to be involved in the general metabolism and structure of the cell. It is suggested that the transition in cell growth from quiescence to the proliferative state, in early G1, may be less specific than previously thought (...) and involve a general priming of the cells for more specific later stimuli. (shrink)

Esta pesquisa avaliou o stress e as estratégias de coping em estudantes de uma universidade pública da região norte de Moçambique. Baseou-se na abordagem qualitativa e envolveu 28 estudantes de ambos os sexos, que cursavam o Curso de Licenciatura em Ensino de Filosofia, os quais responderam a uma entrevista semi-estruturada. A análise de conteúdo da informação coletada revelou a predominância de sintomas de stress de natureza psicológica e diversos estressores acadêmicos, nomeadamente: sobrecarga de matéria e de trabalhos acadêmicos, (...) dificuldades financeiras e econômicas, dificuldades na assimilação da matéria, más relações interpessoais, situações familiares, má atuação dos docentes e insucesso acadêmico. Para gerenciar o stress percebido os estudantes recorrem basicamente às estratégias paliativas. Os achados enfatizam a necessidade de delineamento e implementação de políticas institucionais de promoção de saúde mental dos estudantes, centradas na prevenção de stress e no aconselhamento psicológico. (shrink)

Objectives Older adults are considered one of the most vulnerable groups to COVID-19. However, previous studies on emotion and aging have found that older adults report better well-being than younger adults in global survey and daily report. To better understand older adults’ well-being during the COVID-19 outbreak, we examined age differences in daily affective experiences in this study. Method Two hundred and thirty-one participants from mainland China aged 18 to 85 were recruited to participate in the 14-day daily diary study, (...) after a pretest. Their trait affect and demographic information were measured in the pretest. Their daily affect and stress levels were measured in the daily assessments. Results We found that older adults reported lower perceived stress related to COVID-19 in daily life, compared to younger adults. The negative relationship between daily perceived stress and high arousal positive affect and the positive relationship between daily perceived stress and high arousal negative affect was weaker in older than younger adults. Discussion These results provide initial evidence of daily affective well-being across different age groups in adulthood during the COVID-19 outbreak. Such information is important for developing interventions to promote better well-being during the COVID-19 outbreak. (shrink)

Small non‐coding RNAs (microRNAs or miRs) represent one of the most fertile areas of cancer research and recent advances in the field have prompted us to reconsider the traditional concept of cancer. Some miRs exert negative control over the expression of numerous oncoproteins in normal cells and consequently their deregulation is believed to be an important mechanism underlying cancer development and progression. Owing to their distinct patterns of expression associated with cancer type, remarkable stability and presence in blood and other (...) body fluids, miRs are considered to be highly promising cancer biomarkers. The identification of “miR signatures” associating cancer cell phenotypes with disease outcome and specific risk factor exposures will undoubtedly open new avenues for early diagnosis and therapy of cancer, as well as for the development of novel strategies for cancer prevention. (shrink)

Context can determine whether a given gene acts as an oncogene or a tumor suppressor. Deubiquitinating enzymes (DUBs) regulate the stability of many components of the pathways dictating cell fate so it would be expected that alterations in the levels or activity of these enzymes may have oncogenic or tumor suppressive consequences. In the current review we survey publications reporting that genes encoding DUBs are oncogenes or tumor suppressors. For many DUBs both claims have been made. For such “double (...) agents,” the effects of gain or loss of function will depend on the overall status of a complex of molecular signaling networks subject to extensive crosstalk. As the TGF‐β paradox makes clear context is critical in cell fate decisions, and the disconnect between experimental findings and patient survival outcomes can in part be attributed to disparities between culture conditions and the microenvironment in vivo. Convincing claims for oncogene or tumor suppressor roles require the documentation of gene alterations in patient samples; survival curves are alone inadequate. (shrink)

Stresses on healthcare systems and moral distress among clinicians are urgent, intertwined bioethical problems in contemporary healthcare. Yet conceptualizations of moral distress in bioethical inquiry often overlook a range of routine threats to professional integrity in healthcare work. Using examples from our research on frontline physicians working during the COVID-19 pandemic, this article clarifies conceptual distinctions between moral distress, moral injury, and moral stress and illustrates how these concepts operate together in healthcare work. Drawing from the philosophy of healthcare, (...) we explain how moral stress results from the normal operations of overstressed systems; unlike moral distress and moral injury, it may not involve a sense of powerlessness concerning patient care. The analysis of moral stress directs attention beyond the individual, to stress-generating systemic factors. We conclude by reflecting on how and why this conceptual clarity matters for improving clinicians’ professional wellbeing, and offer preliminary pathways for intervention. (shrink)

Between 1975 and 1985 a series of experiments demonstrated that cancer, whatever its causative agent, is due to the activation, by modification or overexpression, of a family of genes highly conserved during evolution, called the cellular oncogenes. These genes participate in the control of cell division in every living cell. Their products belong to the regulatory network relaying external signals from the membranes towards the nucleus and allowing cells to adapt their division rate to the demand of the organism. These (...) discoveries constitute what may be called the 'oncogene paradigm'. Although the existence of cellular oncogenes, assumed in early models of oncogenesis, was demonstrated as early as 1976, we will show in this article that this discovery was not sufficient for the development of the new paradigm. We will describe its slow and complex formation between 1980 and 1985 followed by its rapid acceptance by the scientific community. (shrink)

The study of adhesion plaques in normal and transformed cells provides a series of phenotypic markers by which the process of transformation can be followed. Several proteins which are concentrated in adhesion plaques have now been identified; a few of these can act as targets for tyrosine kinase. In an attempt to characterize the relationship between tyrosine phosphorylation and cell transformation, the reactions of three such proteins – vinculin, talin and integrin – with a range of tyrosine kinase oncogene products (...) have been studied in detail. (shrink)

We propose that the onset and progressive destructive action of cancer within an individual bears a profound and striking similarity to the onset and progressive human-engendered destruction of global ecosystems and the extinction of entire species. Cancer in the human body and our human role in planetary, especially biotic, degradation are uncannily similar systems. For starters, they are the only two known complex systems where a discrete component changes its normal ecological role and function—turning on and potentially killing its host, (...) and in so doing, itself. Both are “hostile takeovers.” Clearly, humans are integral to both systems. With cancer we are the host and victims of the rogue behavior of what starts out as a normal, healthy, and functionally important part of our bodies. With the biodiversity crisis, we are the part of the system that has changed, expanded, and proven so destructive to the system in which we live. We argue that given that these threats to our bodies and Earth are both essentially ecological diseases, understanding the critical role of ecological interdependencies for avoiding both cancer’s and humankind’s destruction of their respective homes should hopefully promote better stewardship of both by the only animal capable of recognizing the problems—us. (shrink)

The following is adapted from the testimony, on 6 June 1984, of Dr T. G. Krontiris before the U.S. House Science and Technology Subcommittee on Investigations and Oversight, on the subject of oncogene research. In a previous report (BioEssays, 1, 3), the testimony of Dr C. J. Sherr, describing the molecular biology of oncogene action was given. Here, Krontiris describes the challenges in applying the new5ndings in diagnosis and therapy.

Cancer derives from a cell clone that has accumulated genetic and epigenetic changes that influence its phenotype and finally enable it to escape from the normal controls of proliferation. A recent paper shows that, in myc‐induced tumours, the inactivation of this oncogene produces the regression of the tumours and the differentiation of the tumour cells into mature osteocytes.1 In addition, a further reactivation of myc in these cells does not restore the malignant phenotype but induces apoptosis. This discovery could lead (...) to an innovative therapeutic strategy. BioEssays 25:104–107, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Stem cells may have a special importance in the neoplastic behavior of certain lineages as well as in the normal development of these tissues. The role of oncogenes, and their normal cellular analogues, in stem cell behavior is therefore of special interest. This review describes recent results on the effects of virally‐mediated src‐gene transfer into hemopoietic stem cells in the physiological and developmental properties of these cells.

The aim of the present study was to investigate the association between work-related moral stress, moral climate and moral sensitivity in mental health nursing. By means of the three scales Hospital Ethical Climate Survey, Moral Sensitivity Questionnaire and Work-Related Moral Stress, 49 participants’ experiences were assessed. The results of linear regression analysis indicated that moral stress was determined to a degree by the work place’s moral climate as well as by two aspects of the mental health staff’s (...) moral sensitivity. The nurses’ experience of ‘moral burden’ or ‘moral support’ increased or decreased their experience of moral stress. Their work-related moral stress was determined by the job-associated moral climate and two aspects of moral sensitivity. Our findings showed an association between three concepts: moral sensitivity, moral climate and moral stress. Despite being a small study, the findings seem relevant for future research leading to theory development and conceptual clarity. We suggest that more attention be given to methodological issues and developing designs that allow for comparative research in other disciplines, as well as in-depth knowledge of moral agency. Copyright © 2011 by SAGE Publications. (shrink)

Despite the remarkable achievements of novel targeted anti‐cancer drugs, most therapies only produce remission for a limited time, resistance to treatment, and relapse, often being the ultimate outcome. Drug resistance is due to highly efficient adaptive strategies utilized by cancer cells. Exogenous and endogenous stress stimuli are known to induce first‐line responses, capable of re‐establishing cellular homeostasis and determining cell fate decisions. Cancer cells may also mount second‐line adaptive strategies, such as the mutator response. Hypermutable subpopulations of cells may (...) expand under severe selective stress, thereby accelerating the emergence of adapted clones. As with first‐line protective responses, these strategies appear highly conserved, and are found in yeasts and bacteria. We hypothesize that evolutionarily conserved programs rheostatically regulate mutability in fluctuating environments, and contribute to drug resistance in cancer cells. Elucidating the conserved genetic and molecular mechanisms may present novel opportunities to increase the effectiveness of cancer therapies. (shrink)

COVID-19 has resulted in extraordinary disruptions to the higher education landscape. Here, we provide a brief report on 295 students’ academic perceptions and emotional well-being in late May 2020. Students reported the high levels of uncertainty regarding their academic futures as well as significant levels of stress and difficulty coping with COVID-19 disruptions. These outcomes were related to the higher levels of neuroticism and an external locus of control. Female students reported worse emotional well-being compared to males, and the (...) students of color reported the significantly higher levels of stress and uncertainty regarding their academic futures compared to White students. These results suggest that some students may be at particular risk for academic stress and poor emotional well-being due to the pandemic and highlight the urgent need for intervention and prevention strategies. (shrink)

In the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a ‘system biology disease’. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, (...) but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted drug. (shrink)

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult structures (...) solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

Background: The rapid spread of COVID-19 infection has led countries across the globe to take various measures to contain the outbreak, including the closure of Universities. Forcing University students to stay at home has created enormous stress and uncertainty in their daily life.Objective: This study aimed to assess the perceived stress and coping strategies among undergraduate health science students of Jimma University amid the COVID-19 outbreak.Materials and methods: An online cross-sectional survey was conducted involving 337 undergraduate health science (...) students from August to September 5, 2020. The perceived stress scale -10 and Brief-COPE scale were used to assess the level of stress and coping strategies, respectively. Statistical Package for Social Science Version 22 was employed for data analysis. Logistic regression was conducted to identify predictors of high perceived stress.Results: The overall mean [±standard deviation ] age of the participants was 22.88 years. The mean PSS score was 22.16, and high perceived stress was reported in 121 participants. The overall mean coping score was 72.34, and approach coping was the predominantly used strategy for coping with stress. Personal perception of being stressed by the daily number of COVID-19 cases/deaths in Ethiopia, rare online talk/chat with friends, presence of confusion due to the inconsistent strategies developed by the health/government authorities in view of the scientific recommendations, perception of self/family members being at risk of getting sick, decreased household income following the COVID-19 pandemic, practicing denial, self-blame, planning, and religion as means of coping with stress were associated with high perceived stress.Conclusion: Over one-third of the participants had a high level of perceived stress, and the majority of them were practicing effective means of coping with stress. The authors recommend that the hosting University in collaboration with the concerned bodies develop innovative strategies to improve the psychological well-being of the students. (shrink)

Genes that exert their function when they are introduced into a foreign genetic background pose many questions to our current understanding of the forces and mechanisms that promote either the maintenance or divergence of gene functions over evolutionary time. The melanoma inducing Xmrk oncogene of the Southern platyfish (Xiphophorus maculatus) is a stable constituent of the genome of this species. It displays its tumorigenic function, however, almost exclusively only after inter‐populational or, even more severely, interspecific hybridization events. The Xiphophorus hybrid (...) melanoma system has gained attention in biomedical research as a genetic model for studying tumor formation. From an evolutionary perspective, a prominent question is: how could this gene persist over millions of years? An attractive hypothesis is that Xmrk, acting as a detrimental gene in a hybrid genome, could be a speciation gene that shields the gene pool of its species from mixing with other closely related sympatric species. In this article, I briefly review our current knowledge of the molecular genetics and biochemical functions of the Xmrk gene and discuss aspects of its evolutionary history and presence with respect to this idea. While Xmrk as a potentially injurious oncogene has clearly survived for millions of years, its role as a speciation gene has to be questioned. BioEssays 30:822–832, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Stress is prevalent in our daily life, and people often make moral decision-making in a stressful state. Several studies have indicated the influence of acute stress on moral decision-making and behavior. The present study extended the investigation to chronic stress, and employed a new approach, the CNI model, to add new insights regarding the mechanism underlying the association between chronic stress and moral decision-making. A total of 197 undergraduates completed the Perceived Stress Scale and made (...) moral decision-making on a series of deliberately designed moral dilemmas. The results indicated that the high-stress group (one standard deviation above the mean) preferred more deontological options than the low-stress group (one standard deviation below the mean). Process-dissociation analysis revealed that the two groups had differences on deontological inclinations but not on utilitarian inclinations. And CNI model analyses suggested that the high-stress group showed a stronger general preference for inaction than the low-stress group did, but there were no significant differences in sensitivity to consequences or sensitivity to moral norms between the two groups. Finally, the implications of our findings were discussed. (shrink)

Understanding the evolutionary role of environmentally induced phenotypic variation (i.e., plasticity) is an important issue in developmental evolution. A major physiological response to environmental change is cellular stress, which is counteracted by generic stress reactions detoxifying the cell. A model, stress‐induced evolutionary innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types, is described. Previous findings suggest that the cell differentiation cascade (...) of a cell type critical to pregnancy in humans, the decidual stromal cell, evolved from a cellular stress reaction. It is hypothesized that the stress reaction in these cells was elicited ancestrally via inflammation caused by embryo attachment. The present study proposes that SIEI is a distinct form of plasticity‐based evolutionary change leading to the origin of novel structures rather than adaptive transformation of pre‐existing characters. (shrink)

This chapter conceptually analyzes the post-traumatic stress injuries called moral injury, moral fatigue or exhaustion, and broken spirit. It then identifies two puzzles. First, soldiers sometimes sustain moral injury even from doing right actions. Second, they experience moral exhaustion from making decisions even where the morally right choice is so obvious that it shouldn’t be stressful to make it; and even where rightness of decision is so murky that no decision could be morally faulted. The injuries result of mistaken (...) moral self-evaluation. Methods of preventing and treating these injuries are defended, including training in self-forgiveness, moral off-loading of actions and decisions to persons and devices less likely to feel inappropriate guilt, and the use of drugs to prevent such guilt. The foregoing has been about moral injury erroneously resulting from the non-violation of a correct moral code. But the chapter then introduces the concept of moral pseudo-injury—felt moral injury that has in reality resulted from violation of a false moral code, so that no one has really been morally injured. This can be used as a method in warfighting. And since the injuries it produces are illusory, this would be morally superior to physical violence. For it causes less injury to its victims, and should cause less guilt in those who must inflict it. Historical precedents are considered. Finally, our enemies often use moral pseudo-injury against us, in the form of terrorist violence against civilians. Terrorism causes comparatively few harms, yet we mistakenly see it as more morally horrific than conventional combat that causes much worse loss of life among armed forces members. Here we need the nuancing and clarifying power of philosophy to restore a sense of proportion, thence to prevent or therapize the moral pseudo-injury we may experience from these sorts of attacks. (This is a pre-penultimate version of the published version, available from OUP at the external link, which contains minor variances. The paper was earlier known as "PTSD Weaponized: A Theory of Moral Injury"; that now superseded version is archived under "past conferences" on the Center for Ethics and the Rule of Law website.). (shrink)

This study examined the cognitive mechanism underlying acute stress in creative cognition among individuals with high and low trait anxiety. Specifically, cognitive inhibition was assessed using the flanker task during acute stress. Fifty-two participants (26 high trait anxiety, 26 low trait anxiety) (mean age = 18.94 years) underwent stress induction via the Trier Social Stress Test (TSST). They all completed the Alternative Uses Test (AUT) and the Remote Associates Test (RAT) before and after the TSST. Biochemical (...) markers (salivary cortisol and salivary alpha amylase) were recorded at regular intervals. The results showed that cognitive inhibition was influenced by trait anxiety and acute stress. Compared to before experiencing acute stress, there was a lack of cognitive inhibition in low trait anxious individuals and they performed better in AUT (fluency) after acute stress, whereas high trait anxious individuals showed a decreased interference effect and reduced performance in AUT (fluency, flexibility, and originality). In the RAT, there were shorter response times and increased accuracy after acute stress in both high and low trait anxiety groups. Thus, we suggest that cognitive control, which modulates changes in acute stress, influences creative cognition. These findings provide evidence that inhibition control mediates the effect of stress on the creativity of individuals with different trait anxiety. (shrink)

_ Source: _Volume 40, Issue 1, pp 80 - 103 This study was designed to examine the relationships between social support, perceived stress, religiosity, and flourishing and to test the mediating role of perceived stress in the relationships between social support and religiosity with flourishing. This study also examines the moderating roles of religiosity and gender in the relationship between social support and flourishing among 2301 Malaysian older adults. Structural Equation Modelling showed that older adults with high levels (...) of social support, high levels of intrinsic religious motivation, high levels of extrinsic religious motivation, and low levels of perceived stress were more likely to experience flourishing. Bootstrapping analysis provided evidence of perceived stress as a significant partial mediator in the links between social support, intrinsic religious motivation, and extrinsic religious motivation with flourishing. Multi-group analysis revealed that religiosity and gender acted as significant moderators in the links between social support, perceived stress, and flourishing. (shrink)

This study examines differences in parental stress between parentsof Autism Spectrum Disorder children and Typically Developed children in Malaysia. This study also compares the ages of parentsof ASD children with parents of TD children with stress as a variable in theseparents. Parents completed the Parental Stress Index anda socio-demographic questionnaire. Parents with ASD children were found tobe significantly more stressed compared to parents of TD children.Significant scores were also found in the Parent-Child Dysfunctional Interaction sub-scale as well (...) as Difficult Child and ParentalDistress sub-scales with lower significance. Results also indicatethat the 30-35-year-old age group among ASD parents was significantly foundto be more stressed compared with parents of TD children of the same ages.Implications of the findings regarding support and intervention for familieswith ASD are also discussed. (shrink)

Research indicates that the well‐being and productivity of over 100 million people in the global workforce may be compromised by posttraumatic stress (PTS). Given that work‐related experiences are often the source of the trauma that leads to PTS, and that PTS due to any cause can interfere with employees’ job performance, organizations would do well to consider the antecedents and consequences of PTS. This review of research—primarily within fields adjacent to business—on the types, antecedents, consequences, and organizational implications of (...) PTS is presented to advance inquiry within the field of business. The definition of PTS requires attention to the new classification of complex posttraumatic stress disorder that can result from threats that are not life‐threatening such as bullying and sexual harassment. PTS antecedents include organizational and extraorganizational traumas, and risk and resilience factors. Absenteeism, impaired cognitive functioning, strained relationships, and growth are among the consequences of PTS. Organizations can assist through disaster planning, empathetic leaders, mental health literacy initiatives, and employee assistance programs. Many research questions arise that, when answered, will allow organizations to better understand how they can improve employee productivity and well‐being by attending to PTS. (shrink)

From 1942 to 1952, a programme took place at Johns Hopkins to devise new methods of controlling Baltimore’s rat population. This article focuses on three individuals closely connected to this project at various stages of its development: psycho-biologist Curt Richter, animal ecologist David E. Davis, and ecologist and psychologist John B. Calhoun. For all three, the challenges of controlling rat numbers highlighted the significance of stress – a homeostatic mechanism critical to the survival of the animal. This was a (...) process that was analyzed and manipulated by (re)introducing the wild rat into the laboratory. Here the rat not only contributed to new methods of rodent control, but offered new possibilities for the control and improvement of humankind. Yet it was not just the animal, but the physical structure of the laboratory that came to model the world outside. Through examining the experimental systems of the three scientists, this article will trace a series of transgressions between laboratory and field, urban and wild, animal and human. The result was that while animals were used to model the behaviour and pathologies of human city dwellers, the laboratory spaces in which they existed came to model the urban environment. We shall also see how differing perspectives on the value and uses of animal models and environments encouraged and reinforced alternative visions as to the role of science in the service of the city. (shrink)

In a recent paper, Andy Clark (2008) has argued that the literature on embodied cognition reveals a tension between two prominent strands within this movement. On the one hand, there are those who endorse what Clark refers to as body-centrism, a view which emphasizes the special contribution made by the body to a creature’s mental life. Among other things, body centrism implies that significant differences in embodiment translate into significant differences in cognition and consciousness. On the other hand, there are (...) those who endorse what Clark calls extended functionalism, a view which sees the mind as the joint product of the computational resources presented by (i) intracranial processing, (ii) bodily input, and (iii) environmental scaffolding. As such, extended functionalism allows for the possibility that any contribution of the body to cognition and consciousness can be compensated for by the other two contributing factors. While Clark’s sympathies lie with the latter approach, we argue in favour of the former. In particular, we focus on consciousness and argue that the unique contribution the body makes to a creature’s manifold of phenomenal experience cannot be compensated for, in the manner, and on the scale, that Clark envisages. (shrink)

Parenting is a transforming experience for the life of parents that brings joy and satisfaction as well as challenges, frustration, and demands. The aim of this study was to determine the relationship between “parental stress and satisfaction” and work-home conflict, perceived social support, and global satisfaction with life, and to determine the moderating role of the parent's gender. A sample of 244 participants was studied: 49.6% (121) mothers and 50.4% (123) fathers with children between 2 and 12 years of (...) age. The data was analysed by means of multiple linear regression models and Beta regression for stress and parental satisfaction, respectively, and they were complemented with general and conditional dominance analyses to estimate the relevance of the predictors. Mothers presented higher levels of parental stress and satisfaction than fathers. Being female, having two children, and home-work conflict were predictors of a higher parental stress. Age was also a predictor, as younger parents and also those older than 37 years of age showed more parental stress. Having no partner and being male was associated to lower parental satisfaction. In conclusion, parental stress and satisfaction emerge as clearly differentiated dimensions of parenting experience. The gender gap in parental stress could be linked to the persistence of traditional roles regarding the care of the children, in agreement with the findings in other research. (shrink)

The aim of this article is to describe the synthesis of the concept of moral stress and to attempt to identify its preconditions. Qualitative data from two independent studies on professional issues in nursing were analysed from a hypothetical-deductive approach. The findings indicate that moral stress is independent of context-given specific preconditions: (1) nurses are morally sensitive to the patient’s vulnerability; (2) nurses experience external factors preventing them from doing what is best for the patient; and (3) nurses (...) feel that they have no control over the specific situation. The findings from this analysis are supported by recent research on stress in the workplace but differ in that the imperatives directing work are moral in nature. Stress researchers have found that persons who experience that they have no control over their work situation and at the same time experience high demands may be prone to cardiovascular diseases. An important question raised by this study is whether moral stress should be recognized as a health risk in nursing. Further research is required in order to generate intervention models to prevent or deal with moral stress. (shrink)