p90 ribosomal S6 kinases play a significant role in early gene regulation in the cardiomyocyte response to Gq protein-coupled receptor stimuli, endothelin-1 and α1-adrenergic receptor agonists

Extracellular signal-regulated kinases 1/2 (ERK1/2) and their substrates, p90 ribosomal S6 kinases (RSKs), phosphorylate different transcription factors, contributing differentially to transcriptomic profiles. In cardiomyocytes, ERK1/2 are required for >70% of the transcriptomic response to endothelin-1. Here, we investigated the role of RSKs in the transcriptomic responses to Gq protein-coupled receptor agonists, endothelin-1, phenylephrine (generic α1-adrenergic receptor agonist) and A61603 (α1A-adrenergic receptor selective). Phospho-ERK1/2 and phospho-RSKs appeared in cardiomyocyte nuclei within 2-3 min of stimulation (endothelin-1>a61603≈phenylephrine). All agonists increased nuclear RSK2, but only endothelin-1 increased nuclear RSK1 content. PD184352 (inhibits ERK1/2 activation) and BI-D1870 (inhibits RSKs) were used to dissect the contribution of RSKs to the endothelin-1-responsive transcriptome. Of 213 RNAs upregulated at 1 h, 51% required RSKs for upregulation whereas 29% required ERK1/2 but not RSKs. The transcriptomic response to phenylephrine overlapped with, but was not identical to, endothelin-1. As with endothelin-1, PD184352 inhibited upregulation of most phenylephrine-responsive transcripts, but the greater variation in effects of BI-D1870 suggests that differential RSK signalling influences global gene expression. A61603 induced similar changes in RNA expression in cardiomyocytes as phenylephrine, indicating that the signal was mediated largely through α1A-adrenergic receptors. A61603 also increased expression of immediate early genes in perfused adult rat hearts and, as in cardiomyocytes, upregulation of the majority of genes was inhibited by PD184352. PD184352 or BI-D1870 prevented the increased surface area induced by endothelin-1 in cardiomyocytes. Thus, RSKs play a significant role in regulating cardiomyocyte gene expression and hypertrophy in response to Gq protein-coupled receptor stimulation.

Review of the formulation of present‐generation stratospheric chemistry‐climate models and associated external forcings

The goal of the Chemistry‐Climate Model Validation (CCMVal) activity is to improve understanding of chemistry‐climate models (CCMs) through process‐oriented evaluation and to provide reliable projections of stratospheric ozone and its impact on climate. An appreciation of the details of model formulations is essential for understanding how models respond to the changing external forcings of greenhouse gases and ozonedepleting substances, and hence for understanding the ozone and climate forecasts produced by the models participating in this activity. Here we introduce and review the models used for the second round (CCMVal‐2) of this intercomparison, regarding the implementation of chemical, transport, radiative, and dynamical processes in these models. In particular, we review the advantages and problems associated with approaches used to model processes of relevance to stratospheric dynamics and chemistry. Furthermore, we state the definitions of the reference simulations performed, and describe the forcing data used in these simulations. We identify some developments in chemistry‐climate modeling that make models more physically based or more comprehensive, including the introduction of an interactive ocean, online photolysis, troposphere‐stratosphere chemistry, and non‐orographic gravity‐wave deposition as linked to tropospheric convection. The relatively new developments indicate that stratospheric CCM modeling is becoming more consistent with our physically based understanding of the atmosphere.

Satanic Mills? An illustration of Victorian external environmental accounting

The paper evaluates a Victorian environmental account of the pollution of the River Wandle. This account was produced during a period of social and environmental crisis, when there were no significant industrial environmental regulations. This problematising external environmental account provides valuable insights into the historical development of social and environmental accounting. Our analysis located this account within an institutional reform programme to create systems of governance to mitigate the damage arising from unfettered industrial growth. We argue that problematising external environmental accounting has a longer tradition than previously recognised in the literature and predates corporate social and environmental reporting.

Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa

Background Recent evidence has shown that individuals with acute anorexia nervosa and those recovered have aberrant physiological responses to rewarding stimuli. We hypothesized that women recovered from anorexia nervosa would show aberrant neural responses to both rewarding and aversive disorder-relevant stimuli. Methods Using functional magnetic resonance imaging (fMRI), the neural response to the sight and flavor of chocolate, and their combination, in 15 women recovered from restricting-type anorexia nervosa and 16 healthy control subjects matched for age and body mass index was investigated. The neural response to a control aversive condition, consisting of the sight of moldy strawberries and a corresponding unpleasant taste, was also measured. Participants simultaneously recorded subjective ratings of “pleasantness,” “intensity,” and “wanting.” Results Despite no differences between the groups in subjective ratings, individuals recovered from anorexia nervosa showed increased neural response to the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight in the occipital cortex. The recovered participants also showed increased neural response to the aversive strawberry taste in the insula and putamen and to the aversive strawberry sight in the anterior cingulate cortex and caudate. Conclusions Individuals recovered from anorexia nervosa have increased neural responses to both rewarding and aversive food stimuli. These findings suggest that even after recovery, women with anorexia nervosa have increased salience attribution to food stimuli. These results aid our neurobiological understanding and support the view that the neural response to reward may constitute a neural biomarker for anorexia nervosa.

Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment

Background Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. Methods We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key “punishment” areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.

Long duration stimuli and nonlinearities in the neural–haemodynamic coupling

Recent studies have shown that the haemodynamic responses to brief (<2 secs) stimuli can be well characterised as a linear convolution of neural activity with a suitable haemodynamic impulse response. In this paper, we show that the linear convolution model cannot predict measurements of blood flow responses to stimuli of longer duration (>2 secs), regardless of the impulse response function chosen. Modifying the linear convolution scheme to a nonlinear convolution scheme was found to provide a good prediction of the observed data. Whereas several studies have found a nonlinear coupling between stimulus input and blood flow responses, the current modelling scheme uses neural activity as an input, and thus implies nonlinearity in the coupling between neural activity and blood flow responses. Neural activity was assessed by current source density analysis of depth-resolved evoked field potentials, while blood flow responses were measured using laser Doppler flowmetry. All measurements were made in rat whisker barrel cortex after electrical stimulation of the whisker pad for 1 to 16 secs at 5 Hz and 1.2 mA (individual pulse width 0.3 ms).

Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators.

Experientially opening oneself to pain rather than avoiding it is said to reduce the mind's tendency toward avoidance or anxiety which can further exacerbate the experience of pain. This is a central feature of mindfulness-based therapies. Little is known about the neural mechanisms of mindfulness on pain. During a meditation practice similar to mindfulness, functional magnetic resonance imaging was used in expert meditators (> 10,000 h of practice) to dissociate neural activation patterns associated with pain, its anticipation, and habituation. Compared to novices, expert meditators reported equal pain intensity, but less unpleasantness. This difference was associated with enhanced activity in the dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called ‘salience network’, for experts during pain. This enhanced activity during pain was associated with reduced baseline activity before pain in these regions and the amygdala for experts only. The reduced baseline activation in left aI correlated with lifetime meditation experience. This pattern of low baseline activity coupled with high response in aIns and aMCC was associated with enhanced neural habituation in amygdala and pain-related regions before painful stimulation and in the pain-related regions during painful stimulation. These findings suggest that cultivating experiential openness down-regulates anticipatory representation of aversive events, and increases the recruitment of attentional resources during pain, which is associated with faster neural habituation.

Effect of disease-selective predation on prey infected by contact and external sources

We propose and analyze a simple mathematical model for susceptible prey (S)–infected prey (I)–predator (P) interaction, where the susceptible prey population (S) is infected directly from external sources as well as through contact with infected class (I) and the predator completely avoids consuming the infected prey. The model is analyzed to obtain different thresholds of the key parameters under which the system exhibits stability around the biologically feasible equilibria. Through numerical simulations we display the effects of external infection and the infection through contact on the system dynamics in the absence as well as in the presence of the predator. We compare the system dynamics when infection occurs only through contact, with that when it occurs through contact and external sources. Our analysis demonstrates that under a disease-selective predation, stability and oscillations of the system is determined by two key parameters: the external infection rate and the force of infection through contact. Due to the introduction of external infection, the predator and the prey population show limit-cycle oscillations over a range parametric values. We suggest that while predicting the dynamics of such an eco-epidemiological system, the modes of infection and the infection rates might be carefully investigated.

Beyond arousal and valence: the importance of the biological versus social relevance of emotional stimuli

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

Allocation of spatial attention to emotional stimuli depends upon arousal and not valence

Attentional allocation to emotional stimuli is often proposed to be driven by valence and in particular by negativity. However, many negative stimuli are also arousing leaving the question whether valence or arousal accounts for this effect. The authors examined whether the valence or the arousal level of emotional stimuli influences the allocation of spatial attention using a modified spatial cueing task. Participants responded to targets that were preceded by cues consisting of emotional pictures varying on arousal and valence. Response latencies showed that disengagement of spatial attention was slower for stimuli high in arousal than for stimuli low in arousal. The effect was independent of the valence of the pictures and not gender-specific. The findings support the idea that arousal affects the allocation of attention.

Whistle-blowing by external auditors: seeking legitimacy for the South African audit profession?

Auditing is often cited as playing an important role in managing agency-related costs and, accordingly, being integral to the sound functioning of capital markets. There may, however, be more to the attest function than a technical rational practice. By virtue of relying heavily on claims to technical expertise, professionalism, prudential judgement and public confidence, auditing is both a source of legitimacy for organisations and, paradoxically, dependent on claims to legitimacy for its continued existence. From this perspective, recent regulatory developments, purportedly enacted to increase arms-length control over the profession, may not only be about improving perceived audit quality and practice but also about ensuring continued faith in the well-established ‘rituals’ of the assurance function. A reporting duty imposed on South African external auditors, akin to whistle-blowing, is used as a case study to explore this perspective. In doing so, this paper contributes to the scant body of interpretive research on auditing, simultaneously offering one of the first insights into auditing regulation from an African perspective.

Employees' external representation of their workplace: key antecedents

Drawing on attitude theory, this study investigates the drivers of employees' expression of favorable opinions about their workplace. Despite its theoretical and managerial importance, the marketing literature largely ignores the topic. This study advances prior research by developing, and empirically testing, a conceptual framework of the relationship between workgroup support and favorable external representation of the workplace, mediated by emotional responses to this support. The present research investigates four new relationships: between workgroup support and emotional exhaustion, workgroup support and organizational commitment, workgroup support and job satisfaction, and emotional exhaustion and external representation of the workplace. Based on a sample of over 700 frontline service employees, this study finds that workgroup support affects favorable external representation of the workplace through various emotional responses (i.e., emotional exhaustion, organizational commitment and job satisfaction). In addition, the results identify employees' organizational commitment as the most important determinant of favorable external representation of the workplace, followed by job satisfaction and reduced emotional exhaustion. These results suggest that companies should develop practices that encourage workgroup support and organizational commitment to achieve favorable external representation of the workplace.

Purpose in life predicts better emotional recovery from negative stimuli

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation.