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Objective: To examine the effect of final exam stress on the concentrations of leukotriene B4 (LTB4) and vascular endothelial growth factor (VEGF) in the upper airways among healthy and asthmatic individuals., Method: Nasal samples were collected from 12 individuals with asthma and 23 healthy controls early and late in a final exam period, and during a low-stress period in the semester. We determined LTB4 and VEGF concentrations using Enzyme-Linked Immunoassays., Results: Mixed effects analysis of variance models showed that asthmatic participants with allergies in contrast to healthy individuals experienced a decrease in nasal LTB4 during the final exam period as compared to mid-semester (low stress period). There were no significant changes in nasal VEGF across the observation period. Changes in nasal LTB4 and VEGF were not associated with salivary cortisol, exhaled nitric oxide, or spirometric lung function., Conclusions: Our results suggest that nasal LTB4 concentrations change in periods of psychological stress for asthmatic individuals with allergies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cryptochromes are flavoprotein photoreceptors with multiple signaling roles during plant de-etiolation and development. Arabidopsis cryptochromes (cry1 and cry2) absorb light through an oxidized flavin (FADox) cofactor which undergoes reduction to both FADH° and FADH(-) redox states. Since the FADH° redox state has been linked to biological activity, it is important to estimate its concentration formed upon illumination in vivo. Here we model the photocycle of isolated cry1 and cry2 proteins with a three-state kinetic model. Our model fits the experimental data for flavin photoconversion in vitro for both cry1 and cry2, providing calculated quantum yields which are significantly lower in cry1 than for cry2. The model was applied to the cryptochrome photocycle in vivo using biological activity in plants as a readout for FADH° concentration. The fit to the in vivo data provided quantum yields for cry1 and cry2 flavin reduction similar to those obtained in vitro, with decreased cry1 quantum yield as compared to cry2. These results validate our assumption that FADH° concentration correlates with biological activity. This is the first reported attempt at kinetic modeling of the cryptochrome photocycle in relation to macroscopic signaling events in vivo, and thereby provides a theoretical framework to the components of the photocycle that are necessary for cryptochrome response to environmental signals.

Both individuals with asthma and depression show signs of a dysregulated hypothalamus-pituitary-adrenal axis. However, little is known about the cortisol response to stress in the context of co-occurring asthma and depressive mood. Thirty-nine individuals with asthma and 41 healthy controls underwent a combined speech and mental arithmetic stressor. During the course of the laboratory session, salivary cortisol was collected 5 times, with 1 sample at 0min before the stressor and 4 samples at 0, 15, 30 and 45min after the stressor. Depressive mood in the past week was assessed with the Hospital Anxiety and Depression Scale at the beginning of the session. Depressive symptoms moderated cortisol response to the acute stressor, but only among asthmatic patients. Higher depressive mood was associated with a significant increase in cortisol, whereas low depressive mood was associated with no cortisol response. In healthy participants, depressive mood had no substantial effect on cortisol response to the stressor. These findings suggest that depressive mood and chronic inflammatory diseases such as asthma can interact to augment cortisol response to stress., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rationale: Despite the importance of trigger perceptions for asthma diagnosis and management, associations among asthma triggers, affective disorders, and asthma outcome have received little attention., Objectives: Because anxiety and depression are known to influence patients' health reports, we measured and controlled for these affective disorders in analyzing associations among patient perceptions of asthma triggers and asthma treatment outcomes., Methods: Patients from a nationally representative sample of respiratory specialist practices (N = 459) were assessed for clinically significant anxiety and depression and completed questionnaires on asthma triggers, quality of life, and asthma control. Physicians recorded exacerbation and emergency treatment frequencies in the prior year, spirometric lung function, and allergy test results. Hierarchical multiple regressions examined associations among reported trigger factors, anxiety, depression, and asthma outcomes, including quality of life, asthma control, exacerbations, emergencies, and spirometry., Measurements and Main Results: Patients across asthma severity levels were well represented. Anxiety and depression were associated with more frequent nonallergic, in particular psychological, triggers. Controlling for demographics, asthma severity, anxiety, and depression, nonallergic asthma triggers (including psychological triggers) explained substantial portions of variance in asthma control (total of 19.5%, odds ratios [ORs] = 2.07-1.37 for individual triggers), asthma-related quality of life (total of 27.5%, ORs = 3.21-1.49), and general quality of life (total of 11.3%, ORs = 1.93-1.55). Psychological triggers were consistently associated with exacerbations and emergency treatments (ORs = 1.96-2.04) over and above other triggers and affective disorders. Spirometric lung function was largely unrelated to perceived asthma triggers., Conclusions: Patients' perceptions of asthma triggers are important determinants of asthma outcomes, which can help identify individuals at risk for suboptimal asthma management.

We examined whether lifetime exposure to stressful and traumatic events alters hypothalamic-pituitary-adrenal (HPA) axis functioning, as indexed by hair cortisol, regardless of associated psychopathology, among pregnant women of different racial/ethnic backgrounds. 180 women provided hair samples for measurement of integrated cortisol levels throughout pregnancy and information regarding their lifetime exposure to stressful and traumatic life events. Results indicate that increased lifetime exposure to traumatic events was associated with significantly greater hair cortisol over the course of pregnancy. Similarly, greater lifetime exposure to stressful and traumatic events weighted by reported negative impact (over the previous 12 months) was associated with significantly greater hair cortisol during pregnancy. All analyses controlled for maternal age, education, body mass index (BMI), use of inhaled corticosteroids, race/ethnicity, and post-traumatic stress disorder (PTSD) and depressive symptoms. Following stratification by race/ethnicity, associations between stressful and traumatic life events and hair cortisol were found among Black women only. This is the first study to consider associations between lifetime stress exposures and hair cortisol in a sociodemographically diverse sample of pregnant women. Increased exposure to stressful and traumatic events, independent of PTSD and depressive symptoms, was associated with higher cortisol production, particularly in Black women. Future research should investigate the influence of such increased cortisol exposure on developmental outcomes among offspring.

The effect of stress, anxiety and other affective states on inflammatory conditions such as asthma is well documented. Although several immune pathway mechanisms have been proposed and studied, they cannot fully explain the relationship. In this chapter we present a new perspective on asthma development and exacerbation that integrates findings on the role of psychological factors in asthma with the microbiome and the hygiene hypothesis in asthma development.

Background: Hypothalamic-pituitary-adrenal (HPA) axis activity is known to be altered following events such as childhood abuse. However, despite potential adverse consequences for the offspring of women who have experienced abuse, very little is known about altered HPA axis activity during pregnancy., Methods: During pregnancy, 180 women from diverse racial/ethnic backgrounds reported on their exposure to emotional, physical and/or sexual abuse before the age of 11, and general post-traumatic stress symptoms (ie, not limited to childhood years or abuse experiences). Around delivery, they provided hair samples for the assessment of cortisol levels during pregnancy. Hair cortisol was assessed for each pregnancy trimester. The effect of childhood abuse on hair cortisol was assessed using mixed-effects analyses of covariance models allowing for within-subject correlated observations, and were first performed in the entire sample and subsequently stratified by race/ethnicity., Results: Controlling for post-traumatic stress symptoms, hair cortisol levels varied by history of child abuse, F(2,166)=3.66, p=0.028. Childhood physical and/or sexual abuse was associated with greater hair cortisol levels, t(166)=2.65, p=0.009, compared with no history of abuse. Because childhood rates of abuse and hair cortisol levels varied by race/ethnicity, analyses were stratified by race/ethnicity. The associations between history of abuse and cortisol levels were only significant among black women, F(2,23)=5.37, p=0.012., Conclusions: Childhood abuse, especially physical and/or sexual abuse, is associated with differences in cortisol production during pregnancy, particularly among black women. Future research should investigate how these differences impact physical and mental health outcomes among offspring of affected women., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Rationale: Fractional exhaled nitric oxide (FeNO) is known to vary with multiple endogenous and exogenous factors. Laboratory stress and depressive mood have been associated with altered FeNO levels, but little is known about the susceptibility of FeNO to longer-lasting states of psychological stress in asthma., Objectives: We sought to study changes in FeNO, lung function, and endogenous cortisol levels in students in a low-stress period during the academic term and in high-stress periods of up to 5 days during final exams., Methods: One hundred nine participants (35 with asthma) enrolled in a final examination stress study were assessed during the academic term (low stress) and during final exams (high stress). FeNO, spirometric lung function (FEV1, peak flow), salivary cortisol, and negative affect were measured at three time points. Control variables were medication use, cold symptoms, sex, and age., Measurements and Main Results: FeNO decreased substantially from low-stress baseline to the high-stress examination periods, with more pronounced decreases occurring in subjects with asthma (-11.5 ppb) than control subjects (-1.2 ppb). FEV1 decreased in both groups. Negative affect and cortisol increased during final exams, but these increases were smaller in asthma. Greater initial depression and greater cortisol increases were related to larger FeNO decreases during the final exam period, the latter only in asthma. Inhaled corticosteroid use did not affect these changes., Conclusions: Psychological stress and depressive mood are accompanied by decreases in both FeNO and lung function in asthma. Fluctuations related to life stress and mood levels should be considered in FeNO monitoring for asthma.

The avian magnetic compass, probably based on radical pair processes, works only in a narrow functional window around the local field strength, with cryptochrome 1a as most likely receptor molecule. Radio-frequency fields in the MHz range have been shown to disrupt the birds' orientation, yet the nature of this interference is still unclear. In an immuno-histological study, we tested whether the radio-frequency fields interfere with the photoreduction of cryptochrome, but this does not seem to be the case. In behavioural studies, birds were not able to adjust to radio-frequency fields like they are able to adjust to static fields outside the normal functional range: neither a 2-h pre-exposure in a 7.0 MHz field, 480 nT, nor a 7-h pre-exposure in a 1.315 MHz field, 15 nT, allowed the birds to regain their orientation ability. This inability to adjust to radio-frequency fields suggests that these fields interfere directly with the primary processes of magnetoreception and therefore disable the avian compass as long as they are present. They do not have lasting adverse after-effects, however, as birds immediately after exposure to a radio-frequency field were able to orient in the local geomagnetic field., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)

Cryptochromes are blue-light absorbing flavoproteins with multiple signaling roles. In plants, cryptochrome (cry1, cry2) biological activity has been linked to flavin photoreduction via an electron transport chain to the protein surface comprising 3 evolutionarily conserved tryptophan residues known as the 'Trp triad.' Mutation of any of the Trp triad residues abolishes photoreduction in isolated cryptochrome protein in vitro and therefore had been suggested as essential for electron transfer to the flavin. However, photoreduction of the flavin in Arabidopsis cry2 proteins occurs in vivo even with mutations in the Trp triad, indicating the existence of alternative electron transfer pathways to the flavin. These pathways are potentiated by metabolites in the intracellular environment including ATP, ADP, AMP, and NADH. In the present work we extend these observations to Arabidopsis cryptochrome 1 and demonstrate that Trp triad substitution mutants at W400F and W324F positions which are not photoreduced in vitro can be photoreduced in whole cell extracts, albeit with reduced efficiency. We further show that the flavin signaling state (FADH°) is stabilized in an in vivo context. These data illustrate that in vivo modulation by metabolites in the cellular environment may play an important role in cryptochrome signaling, and are discussed with respect to possible effects on the conformation of the C-terminal domain to generate the biologically active conformational state.

Background: Research suggests that elevated stress hormones during exposure can facilitate fear extinction in laboratory settings. However, prospective studies on the clinical benefits of endogenous cortisol on clinical improvements in naturalistic exposures are lacking., Methods: Twenty-six patients with panic disorder and agoraphobia completed three weekly in-vivo exposure sessions and a fourth session 2 months following therapy completion, resulting in a total of 94 in-vivo exposure sessions. Salivary cortisol was collected at multiple times during the first exposure day (cortisol morning response, prior, -during, -after exposure) and at subsequent exposure sessions (prior, -during, -after exposure). Cortisol collection on a non-exposure comparison day followed the same time schedule as session 1., Results: Exposure day anxiety and cortisol levels were significantly higher than control day levels. Higher absolute cortisol levels during exposures moderated clinical improvement (avoidance behavior, threat appraisal, perceived control). Therapeutic gains were not just related to exposure day cortisol levels, but were also linked to non-exposure day levels. Greater morning rises in cortisol on exposure day predicted greater treatment gains, but greater rises on the control day were associated with poorer outcomes., Conclusions: The study provides first evidence for a moderating effect of cortisol awakening response and absolute cortisol levels on fear extinction processes during naturalistic, prospective exposure-therapy. Additionally, we replicated and extended prior findings on the therapeutic benefits of high exposure cortisol levels. Together, the findings suggest that cortisol may act as a general moderator of facilitated learning during exposure therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Increases in fractional exhaled nitric oxide (FeNO) have been observed after acute laboratory stress, which could indicate a strengthening of immune defenses in acute stress because of the quick onset of the response and the role of nitric oxide in airway-protective functions. In addition, because sustained psychological distress and depression are known to deteriorate immune defenses systems, they may dampen the FeNO response to acute stress., Methods: FeNO and negative affect were measured before and after a speech and mental arithmetic stressor. We examined the association of stress-induced FeNO changes with momentary negative affect and questionnaires of perceived stress, anxious mood, and depressive mood in 39 asthma patients and 41 healthy controls., Results: FeNO increased from baseline to stress in participants with asthma (from 3.38 [0.102] to 3.46 [0.103] ln(ppb)) and controls (2.86 [0.098] to 2.92 [0.099]; F(4,141) = 3.26, p = .014), but the magnitude of the FeNO response did not differ between groups (F < 1). Only low levels of depressive mood were associated with FeNO increases after stress (most pronounced at 0 minute poststress; t(76) = 3.87, p < .001). In contrast, only higher perceived stress was associated with FeNO increases (most pronounced at 0 minute poststress; t(75) = 4.09, p < .001), and momentary negative affect was associated with higher FeNO throughout assessments (β = 0.08, t(114) = 8.27, p = .005). Associations of FeNO with psychological variables were largely unrelated to asthma status and inhaled corticosteroid use., Conclusions: Depressive mood is associated with a reduced mobilization of airway nitric oxide in acute stress, whereas other indicators of negative affect are positively associated with overall FeNO levels and reactivity.

Background: Hyperventilation has been associated with adverse effects on lung function, symptoms, and well-being in asthma. We examined whether raising end-tidal CO2 levels (ie, Pco2) compared with slow breathing is associated with improvements in asthma control, including peak flow variability., Methods: One hundred twenty patients with asthma were randomly assigned to capnometry-assisted respiratory training (CART) for raising Pco2 or slow breathing and awareness training (SLOW) for slowing respiratory rate. Patients received five weekly sessions and completed bid homework exercises over 4 weeks. Blinded assessments at baseline, posttreatment, 1- and 6-month follow-up of asthma control, Pco2, and diurnal peak flow variability were primary outcome measures. Additionally, we measured pulmonary function (spirometry, forced oscillation, exhaled nitric oxide, and methacholine challenge), symptoms, quality of life, and bronchodilator use. Because the control group received active treatment, we expected improvements in asthma control in both groups but more pronounced benefits from CART., Results: Improvements were seen in 17 of 21 clinical indexes (81.0%) in both interventions, including the primary outcome variables asthma control (d = 0.81), peak flow variability (d = 0.54), quality of life, bronchodilator use, lung function, and airway hyperreactivity. Most improvements were sustained across the 6-month follow-up. Compared with slow breathing, CART showed greater increases in Pco2 (d = 1.45 vs 0.64 for CART vs SLOW, respectively) and greater reductions in respiratory impedance during treatment, less distress during methacholine challenge, and greater reduction in asthma symptoms at follow-up (P < .05)., Conclusions: Brief interventions aimed at raising Pco2 or slowing respiratory rate provide significant, sustained, and clinically meaningful improvements in asthma control. Raising Pco2 was associated with greater benefits in aspects of lung function and long-term symptoms., Trial Registry: ClinicalTrials.gov; No.: NCT00975273; URL: www.clinicaltrials.gov.

Asthma triggers have been linked to adverse health outcomes in asthma, but little is known about their association with asthma control. Because trigger avoidance is an integral part of successful asthma management, psychological triggers in particular may be associated with suboptimal asthma control, given the difficulty of controlling them. We examined cross-sectional and longitudinal associations of perceived asthma triggers with self-report of asthma control impairment, symptoms, and spirometric lung function (forced expiratory volume in the 1st second, [FEV1]) in 179 adult primary care asthma patients. Perceived asthma triggers explained up to 42.5% of the variance in asthma control and symptoms, but not in FEV1 alone. Allergic triggers explained up to 12.1% of the asthma control and symptom variance, three nonallergic trigger types, air pollution/irritants, physical activity, and infection, explained up to 26.2% over and above allergic triggers, and psychological triggers up to 9.5% over and above all other triggers. Psychological triggers alone explained up to 33.9% of the variance and were the only trigger class that was consistently significant in all final multiple regression models predicting control and symptoms. Psychological triggers also predicted lower asthma control 3-6 months later, although controlling for initial asthma control eliminated this association. In free reports of individually relevant triggers, only psychological triggers were associated with suboptimal asthma control. Trigger factors are important predictors of self-reported asthma control and symptoms but not actual lung function. Particular attention should be directed to psychological triggers as indicators of patients' perceptions of suboptimal asthma control.

Psychosocial factors such as social support and depression have long been associated with health outcomes. Elevated depressive symptoms are usually associated with worse health outcomes, whereas social support has been related to improvements in health. Nitric oxide levels are an important marker of both cardiovascular health and immune function. Research suggests that exhaled nitric oxide is affected by stress, negative affect, and depression; however, the effect of social support has not been previously explored. Thus, we sought to examine the association of social support, negative affect, and depression with exhaled nitric oxide in a group of 35 healthy individuals (10 males and 25 females) with a mean age of 20.5years across five weekly assessments. Results showed that changes in social support within individuals were positively associated with levels of exhaled nitric oxide independent of other psychosocial factors. Further exploration of the health implications of this positive relationship between airway nitric oxide and social support is necessary., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life., Aims: To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task., Study Design: Observational repeated measures study., Subjects: Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants., Outcome Measures: Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained., Results: Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers., Conclusions: Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cryptochromes are flavoproteins that drive diverse developmental light-responses in plants and participate in the circadian clock in animals. Plant cryptochromes have found application as photoswitches in optogenetics. We have studied effects of pH and ATP on the functionally relevant photoreduction of the oxidized FAD cofactor to the semi-reduced FADH(·) radical in isolated Arabidopsis cryptochrome 1 by transient absorption spectroscopy on nanosecond to millisecond timescales. In the absence of ATP, the yield of light-induced radicals strongly decreased with increasing pH from 6.5 to 8.5. With ATP present, these yields were significantly higher and virtually pH-independent up to pH 9. Analysis of our data in light of the crystallographic structure suggests that ATP-binding shifts the pKa of aspartic acid D396, the putative proton donor to FAD·(-), from ~7.4 to >9, and favours a reaction pathway yielding long-lived aspartate D396(-). Its negative charge could trigger conformational changes necessary for signal transduction.

Objective: The fraction of exhaled nitric oxide (FeNO) has been widely used as a marker of airway inflammation in asthma in recent years. However, NO serves multiple functions throughout the organism, and various influences on FeNO levels beyond inflammation have been documented. Emerging literature indicates that psychological processes are systematically linked to FeNO., Data Sources: Academic Search Complete, PubMed, PsychArticles, and PsychInfo databases., Study Selections: Relevant studies were identified using keywords exhaled nitric oxide paired with psychological stress, stress psychology, emotion, major depression, anxiety, or psychopathology. Studies measuring FeNO during naturalistic observation of emotion and stress, laboratory stress and emotion-induction protocols, and correlational designs using psychological questionnaires were included., Results: Acute stress, anxiety, and negative affect have been repeatedly linked with higher FeNO levels, whereas more prolonged states of stress, in particular depression, have been associated with lower FeNO levels. The literature on FeNO is paralleled by research on NO in the cardiovascular and central nervous systems, which also shows systematic associations with psychosocial variables. Potential mechanisms of association include stimulation of NO release from different cells, including the epithelia and macrophages, through noradrenaline, interferon-γ, or vascular endothelial growth factor, changes in oxidative stress or arginase levels, or facilitation of diffusion by mechanical factors., Conclusion: Psychosocial factors may need to be considered in the interpretation of longitudinal FeNO changes in monitoring and management of patients with asthma. The distinction between constitutive and inducible sources of NO will be essential for future research., (Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Exposure to feared stimuli in blood-injection-injury (BII)-phobia is thought to elicit a diphasic response pattern, with an initial fight-flight-like cardiovascular activation followed by a marked deactivation and possible fainting (vasovagal syncope). However, studies have remained equivocal on the importance of such patterns. We therefore sought to determine the prevalence and clinical relevance of diphasic responses using criteria that require a true diphasic response to exceed cardiovascular activation of an emotional episode of a negative valence and to exceed deactivation of an emotionally neutral episode. Sixty BII-phobia participants and 20 healthy controls were exposed to surgery, anger and neutral films while measuring heart rate, blood pressure, respiratory pattern, and end-tidal partial pressure of carbon dioxide (as indicator of hyperventilation). Diphasic response patterns were observed in up to 20% of BII-phobia participants and 26.6% of healthy controls for individual cardiovascular parameters. BII-phobia participants with diphasic patterns across multiple parameters showed more fear of injections and blood draws, reported the strongest physical symptoms during the surgery film, and showed the strongest tendency to hyperventilate. Thus, although only a minority of individuals with BII phobia shows diphasic responses, their occurrence indicates significant distress. Respiratory training may add to the treatment of BII phobia patients that show diphasic response patterns., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Nitric oxide (NO) has beneficial effects on cardiovascular and immune health. Stress and depression have been linked to a reduction in serum NO. In this study, we examined the effect of academic exam stress on the fraction of NO in exhaled air (FeNO) and spirometric lung function in 41 healthy college students. Participants completed assessments at mid-semester as well as in the early and late phase of an academic exam period. Negative affect, depressive mood, and salivary cortisol were elevated during exams, whereas FeNO and lung function decreased. Higher depressive mood was associated with lower FeNO, whereas higher negative affect was associated higher FeNO across time. These findings provide initial evidence that depression and prolonged stress can alter FeNO and lung function in healthy individuals, which could have adverse consequences for cardiovascular, airway, and immune health., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: This review examines the evidence for psychosocial influences in asthma and behavioral medicine approaches to its treatment., Method: We conducted a systematic review of the literature on psychosocial influences and the evidence for behavioral interventions in asthma with a focus on research in the past 10 years and clinical trials. Additional attention was directed at promising new developments in the field., Results: Psychosocial factors can influence the pathogenesis and pathophysiology of asthma, either directly through autonomic, endocrine, immunological, and central nervous system mechanisms or indirectly through lifestyle factors, health behaviors, illness cognitions, and disease management, including medication adherence and trigger avoidance. The recent decade has witnessed surging interest in behavioral interventions that target the various pathways of influence. Among these, self-management training, breathing training, and exercise or physical activation programs have proved particularly useful, whereas other essential or promising interventions, such as smoking cessation, dietary programs, perception and biofeedback training, and suggestive or expressive psychotherapy, require further, more rigorous evaluation. Given the high comorbidity with anxiety and mood disorders, further evaluation of illness-specific cognitive behavior therapy is of particular importance. Progress has also been made in devising community-based and culturally tailored intervention programs., Conclusion: In concert with an essential medication treatment, behavioral medicine treatment of asthma is moving closer toward an integrated biopsychosocial approach to disease management.

Stress and infections have long been independently associated with asthma pathogenesis and exacerbation. Prior research has focused on the effect of psychological stress on Th cells with particular relevance to atopic asthma. In this review, we propose new perspectives that integrate the role of infection in the relationship between psychological stress and asthma. We highlight the essential role of the mucosal epithelia of the airways in understanding the interaction between infections and the stress-asthma relationship. In addition, we review findings suggesting that psychological stress not only modulates immune processes, but also the pathogenic qualities of bacteria, with implications for the pathogenesis and exacerbation asthma., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Research suggests that psychological stress can exacerbate allergies, but relatively little is known about the effect of stress on mucosal immune processes central to allergic pathophysiology. In this study, we quantified vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), and interleukin-4 concentrations in saliva (S) and exhaled breath condensate (EBC) during final exams and at midsemester among 23 healthy and 21 allergic rhinitis individuals. IFN-γs decreased during exams for both groups while VEGF(EBC) increased (and increases in VEGFs were a trend). Elevated negative affect ratings predicted higher VEGF(EBC) in allergic individuals. IFN-γ(EBC) increased in healthy individuals early during exams and then decreased, while allergic individuals showed a decrease in IFN-γ(EBC) throughout final exams. These findings suggest that psychological stress can suppress cellular immune function among allergic individuals while increasing VEGF., (Copyright © 2012 Society for Psychophysiological Research.)

Understanding asthma symptom perception is necessary for reducing unnecessary costs both for asthma sufferers and society and will contribute to improving asthma management. The primary aim of this study was to develop and test a standardized method for classification of asthma perceiver categories into under-, normal, and overperceiver groups based on the comparison between self-report and lung function components of asthma control. Additionally, the degree to which demographic variables and anxiety contributed to the classification of patients into perceiver groups was examined. Patients underwent methacholine or reversibility testing to confirm asthma diagnosis. Next, participants completed lung function testing over 3 days before their next appointment. Finally, patients filled out demographic and self-report measures including the Asthma Control Test (ACT). Each self-report category of control assessed by the ACT (interference, shortness of breath, nighttime awakenings, rescue inhaler usage, and a composite total score) was compared with lung function measurements using a modified version of the asthma risk grid. Using the modified asthma risk grid to determine perceiver categorization, this sample included 14 underperceivers, 29 normal perceivers, and 36 overperceivers. A discriminant analysis was performed that indicated that a majority of underperceivers were characterized by being African American and having low asthma-specific anxiety. Normal perceivers in this sample tended to be older. Overperceivers tended to be female. Our findings encourage further research using the reported method of classifying asthma patients into perceiver categories.

Targeted nanomedicine holds enormous potential for advanced diagnostics and therapy. Although it is known that nanoparticles accumulate in liver in vivo, the impact of cell-targeting particles on the liver, especially in disease conditions, is largely obscure. We had previously demonstrated that peptide-conjugated nanoparticles differentially impact macrophage activation in vitro. We thus comprehensively studied the distribution of gold nanorods (AuNR) in mice in vivo and assessed their hepatotoxicity and impact on systemic and hepatic immune cells in healthy animals and experimental liver disease models. Gold nanorods were stabilized with either cetyltrimethylammonium bromide or poly(ethylene glycol) and additional bioactive tripeptides RGD or GLF. Gold nanorods mostly accumulated in liver upon systemic injection in mice, as evidenced by inductively coupled plasma mass spectrometry from different organs and by non-invasive microcomputerized tomography whole-body imaging. In liver, AuNR were only found in macrophages by seedless deposition and electron microscopy. In healthy animals, AuNR did not cause significant hepatotoxicity as evidenced by biochemical and histological analyses, even at high AuNR doses. However, flow cytometry and gene expression studies revealed that AuNR polarized hepatic macrophages, even at low doses, dependent on the respective peptide sequence, toward M1 or M2 activation. While peptide-modified AuNR did not influence liver scarring, termed fibrosis, in chronic hepatic injury models, AuNR-induced preactivation of hepatic macrophages significantly exacerbated liver damage and disease activity in experimental immune-mediated hepatitis in mice. Bioactively targeted gold nanoparticles are thus potentially harmful in clinically relevant settings of liver injury, as they can aggravate hepatitis severity.

Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory-based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated modulation of airway responses to standard airway challenges with exercise, allergens, or pharmacological agents by psychological factors. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood, and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

Background: Individuals with asthma have been shown to respond to unpleasant stimuli with bronchoconstriction, but little is known about the time course of responding during sustained emotional stimulation and whether it varies with patients' experience., Objective: To examine the time course of oscillatory resistance (R(os)) during emotionally evocative films in 15 asthma patients and 14 healthy controls., Methods: Participants viewed unpleasant, surgery, and neutral films, each ranging 3-5min in duration. R(os) and the respiratory pattern (respiration rate, tidal volume, minute ventilation) were monitored continuously. Following each film, participants rated their affective response and symptoms. The time course of R(os) during films was explored using multilevel modeling., Results: Compared to neutral film sequences, unpleasant films (including those with surgery scenes) elicited a uniform pattern of initial increases in R(os) with peaks within the first 1-2min, followed by a gradual decline. Increases were more pronounced in asthma and during surgery films. Including additional respiratory parameters as time-varying covariates did not affect the temporal course of R(os) change. The rate of decline in R(os) (after the initial increase) was less in participants who experienced greater arousal and in patients who reported more shortness of breath. Patients more susceptible to psychological triggers in daily life showed slower rates of decline in R(os)., Conclusion: The temporal course of bronchoconstriction to unpleasant stimulation is highly uniform in asthma, with strong constriction in early stages of stimulation. More sustained constriction in emotion-induced asthma could be a risk factor for developing asthma exacerbation in daily life., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease and associated with considerable individual and socioeconomic burden. Recent research started examining the role of psychosocial factors for course and management of the disease., Purpose: This review provides an overview on recent findings on psychosocial factors and behavioral medicine approaches in COPD., Results: Research has identified several important psychosocial factors and effective behavioral medicine interventions in COPD. However, there is considerable need for future research in this field., Conclusions: Although beneficial effects of some behavioral medicine interventions have been demonstrated in COPD, future research efforts are necessary to study the effects of distinct components of these interventions, to thoroughly examine promising but yet not sufficiently proven interventions, and to develop new creative interventions.

Hyperventilation-induced hypocapnia is common among asthma patients. This case study illustrates both methodology and results from a patient undergoing training in capnometry-assisted respiratory training (CART). CART is a 4-week training aimed at normalizing basal and acute levels of end-tidal carbon dioxide (PCO(2)) using a portable capnometer. In the presented case, basal levels of PCO(2) increased from hypocapnic to normocapnic range over the course of treatment. Improvements were accompanied by improvements in lung function and reductions in diurnal lung function variability. Improvements remained stable throughout follow-up.

Previous research suggests that acute stress can increase the release of immune-relevant proteins in saliva. However, no attempts have been made to examine a wider range of salivary proteins in response to stress. In this study, we identified and quantified changes in the pattern of salivary protein release in a 45 min time period following the Trier Social Stress Test (TSST) in 12 asthmatic and 13 healthy participants. Proteins were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The relative protein amounts were quantified using the Image J software (NIH), and identified and characterized using mass spectroscopy. Negative affect was increased immediately after stress in both groups. The results showed that alpha amylase, cystatin S and light chain IgA were increased after the TSST and significant increases in glutathione S-transferase and prolactin inducible protein were also observed. Asthma patients showed responses similar to healthy controls, but had a tendency toward overall lower alpha amylase levels. Our findings suggest that a variety of proteins relevant to mucosal immunity are elevated following acute psychosocial stress, including glutathione S-transferase and prolactin inducible protein, which had not been characterized in this context before., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0-58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology.

Background: Spontaneous or unexpected panic attacks, per definition, occur "out of the blue," in the absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of, or during, the attack, but not preceding it. To test this hypothesis, we examined if points of significant autonomic changes preceded the onset of spontaneous panic attacks., Methods: Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen natural panic attacks were recorded during 1960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before and continuing to 10 minutes after the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization and compared with time matched control periods within the same person., Results: Significant patterns of instability across a number of autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes before onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt carbon dioxide partial pressure increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in carbon dioxide partial pressure. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before, and during, the attacks. Changes in the matched control periods were largely absent., Conclusions: Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction between uncued and cued panic attacks., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Most of the currently known light-harvesting complexes 2 (LH2) rings are formed by 8 or 9 subunits. As of now, questions like "what factors govern the LH2 ring size?" and "are there other ring sizes possible?" remain largely unanswered. Here, we investigate by means of molecular dynamics (MD) simulations and stochastic modeling the possibility of predicting the size of an LH2 ring from the sole knowledge of the high resolution crystal structure of a single subunit. Starting with single subunits of two LH2 rings with known size, that is, an 8-ring from Rs. moliscianum (MOLI) and a 9-ring from Rps. acidophila (ACI), and one with unknown size (referred to as X), we build atomic models of subunit dimers corresponding to assumed 8-, 9-, and 10-ring geometries. After inserting each of the dimers into a lipid-water environment, we determine the preferred angle between the corresponding subunits by three methods: (1) energy minimization, (2) free MD simulations, and (3) potential of mean force calculations. We find that the results from all three methods are consistent with each other, and when taken together, it allows one to predict with reasonable level of confidence the sizes of the corresponding ring structures. One finds that X and ACI very likely form a 9-ring, while MOLI is more likely to form an 8-ring than a 9-ring. Finally, we discuss both the merits and limitations of all three prediction methods., (Copyright © 2011 Wiley-Liss, Inc.)

Background and Aims: Gating models of sensory perception suggest that increased attention towards the self leads to more on-line processing of sensory information and less report bias. However, little is known about the interaction of self-awareness with fearful beliefs about bodily sensations. In the present study, we explored report bias of breathing-related sensation under increased self-awareness compared to increased focus on external cues related to breathlessness. We expected report bias under internal focus to be lower than under external focus. However, we expected this effect of internal focus to be moderated by fearful beliefs about bodily sensations., Methods: Thirty participants completed two appointments in which attention was directed either towards the self or towards the surroundings. On both sessions, participants' detection threshold for inspiratory loads, negative mood, and fear of bodily sensations was assessed. Changes in threshold were tested using repeated measures ANOVA. The role of fear of bodily sensations was tested in a within-subject moderation analysis., Results and Conclusion: Relative over report of sensations was lower under internal focus compared to external focus. However, this effect was moderated by fear of bodily sensations: the greater fear of bodily sensations was, the lower the effect of self-awareness. Results encourage research on the interaction of self-awareness and fearful beliefs in the top-down modulation of perception., (©2010 The British Psychological Society.)

Rationale: psychosocial stress is known to influence the pathophysiology of asthma. Although stress has been linked to serum markers of inflammatory activity and exaggerated response to allergen challenge in asthma, few studies have examined inflammatory activity in the airways linked to psychosocial stress alone. Furthermore, although studies have demonstrated lower levels or reactivity of endogenous cortisol in asthma, the association with airway inflammatory activity in stress remains unexplored., Objectives: we therefore studied airway inflammation and cortisol response to a standardized laboratory task inducing acute psychosocial stress., Methods: airway inflammation by the fraction of exhaled nitric oxide (FeNO) and saliva cortisol were sampled before and up to 45 minutes after experimental challenge with the Trier Social Stress Test in 20 adult patients with asthma and 19 healthy control subjects. Respiratory inductive plethysmography was used to control for changes in ventilatory activity that impact FeNO levels., Measurements and Main Results: FeNO levels were generally higher in patients with asthma than healthy control subjects and salivary cortisol levels were lower. Increases in cortisol levels were observed after the stress protocol in both groups (P < 0.001). FeNO levels at the time of peak cortisol increase after stress were significantly higher than before stress in both groups (P < 0.05). FeNO increases were independent of changes in ventilation. In patients with asthma, higher cortisol levels and stronger increases in cortisol after stress were significantly associated with smaller increases in FeNO (P < 0.05)., Conclusions: acute psychosocial stress alone increases airway inflammatory markers and this increase is attenuated by stronger stress-related activity of the hypothalamic-pituitary-adrenal axis in asthma.

Earlier research found autonomic and airway reactivity in asthma patients when they were exposed to blood-injection-injury (BII) stimuli. We studied oscillatory resistance (R(os)) in asthma and BII phobia during emotional and disease-relevant films and examined whether muscle tension counteracts emotion-induced airway constriction. Fifteen asthma patients, 12 BII phobia patients, and 14 healthy controls viewed one set of negative, positive, neutral, BII-related, and asthma-related films with leg muscle tension and a second set without. R(os), ventilation, cardiovascular activity, and skin conductance were measured continuously. R(os) was higher during emotional compared to neutral films, particularly during BII material, and responses increased from healthy over asthmatic to BII phobia participants. Leg muscle tension did not abolish R(os) increases. Thus, the airways are particularly responsive to BII-relevant stimuli, which could become risk factors for asthma patients., (Copyright © 2010 Society for Psychophysiological Research.)

Cryptochromes are flavoprotein photoreceptors first identified in Arabidopsis thaliana, where they play key roles in growth and development. Subsequently identified in prokaryotes, archaea, and many eukaryotes, cryptochromes function in the animal circadian clock and are proposed as magnetoreceptors in migratory birds. Cryptochromes are closely structurally related to photolyases, evolutionarily ancient flavoproteins that catalyze light-dependent DNA repair. Here, we review the structural, photochemical, and molecular properties of cry-DASH, plant, and animal cryptochromes in relation to biological signaling mechanisms and uncover common features that may contribute to better understanding the function of cryptochromes in diverse systems including in man.

Blood-injection-injury (BII) phobia is an anxiety disorder that may be accompanied by vasovagal fainting during confrontation with the feared stimuli. The underlying pattern of autonomic regulation has been characterized as a diphasic response, with initial increases in heart rate and blood pressure that are typical of a fight-flight response, and subsequent drops in blood pressure and/or heart rate that may precipitate vasovagal fainting. Tensing skeletal muscles of the arms, legs, and trunk (applied tension) has been proposed as a technique to cope with this dysregulation. This review critically examines the empirical basis for the diphasic response and its treatment by applied tension in BII phobia. An alternative perspective on the psychophysiology of BII phobia and vasovagal fainting is offered by focusing on hypocapnia that leads to cerebral blood flow reductions, a perspective supported by research on neurocardiogenic and orthostatically-induced syncope. The evidence may indicate a role for respiration-focused coping techniques in BII phobia., (2010 Elsevier B.V. All rights reserved.)

Background: The effects of physical activity on asthma have been explored extensively. Exercise can trigger later bronchoconstriction in many patients, and deconditioning due to a sedentary lifestyle may be the consequence. However, the immediate effect of physical activity in asthma and health is bronchodilation. To date, little is known about the association between physical activity and lung function in the daily life of asthma patients., Methods: We studied 20 individuals with asthma and 20 control subjects using an electronic diary of activities and spirometry (peak expiratory flow [PEF], FEV(1)). Participants rated their shortness of breath and their intensity of physical and social activity for the preceding 30 min. Assessments were made over the course of 3 weeks, tid (morning, afternoon, evening/night)., Results: Stronger physical activity was concurrently associated with significantly higher lung function. In contrast, it also showed a positive concurrent association with shortness of breath. In prospective cross-lag analyses, lower PEF and FEV(1) earlier in the day predicted lower physical and social activity levels later in the day, but shortness of breath did not., Conclusion: The findings show that detrimental effects observed in exercise-induced bronchoconstriction cannot be generalized to physical activity in daily lives of individuals with asthma. Nevertheless, people with asthma still feel more shortness of breath when being more physically active. They adjust their activity levels throughout the day according to their earlier lung function, but this does not fully explain the concurrent positive association of physical activity and lung function.

Objective: Previous asthma diary studies have yielded equivocal findings on concurrent associations between lung function and mood, and prospective associations have rarely been explored. We therefore examined concurrent and prospective associations between daily mood, shortness of breath, and lung function, and studied between-individual variability and stability of concurrent associations across different times of the day., Method: Twenty asthma patients and 20 healthy controls recorded their positive and negative mood, shortness of breath, physical activity, peak expiratory flow (PEF) and forced expiratory volume in the first second (FEV(1)) using an electronic pocket spirometer with diary functions three times per day for about 21 days., Results: For both groups, PEF showed positive concurrent associations with ratings of various mood states, whereas FEV(1) was only associated with positive mood. Both indices correlated negatively with shortness of breath. Within-individual concurrent associations varied significantly in both groups and their stability varied across time of the day, with overall higher stability for associations with shortness of breath in asthma and PEF for both groups. Prospectively, higher shortness of breath consistently predicted lower lung function later during the day and on the subsequent day., Conclusion: The relationship between normal mood variations and lung function is highly variable across individuals and times of the day, limiting the predictive value of average group associations. Shortness of breath is predictive of future lung function decline in asthma. Future longitudinal research should focus on extreme emotional states, effort-independent measures of lung function, and additional indicators of asthma control., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Sustained or spontaneous hyperventilation has been associated with a variety of physical symptoms and has been linked to a number of organic illnesses and mental disorders. Theories of panic disorder hold that hyperventilation either produces feared symptoms of hypocapnia or protects against feared suffocation symptoms of hypercapnia. Although the evidence for both theories is inconclusive, findings from observational, experimental, and therapeutic studies suggest an important role of low carbon dioxide (CO2) levels in this disorder. Similarly, hypocapnia and associated hyperpnia are linked to bronchoconstriction, symptom exacerbation, and lower quality of life in patients with asthma. Raising CO2 levels by means of therapeutic capnometry has proven beneficial effects in both disorders, and the reversing of hyperventilation has emerged as a potent mediator for reductions in panic symptom severity and treatment success., (2010 Elsevier B.V. All rights reserved.)

In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma.

Objectives: The affective dimension of illness representation plays an important role in asthma self-management. However, little is known about the stability of this affective representation across contexts. We explored the role of social comparison in this affective evaluation., Design and Methods: Participants included 20 individuals reporting an asthma diagnosis and 33 healthy controls. To measure asthma attitudes, we used three different versions of the Implicit Association Test (IAT), a single target IAT (ST-IAT) and two IATs with different social comparison standards for asthma evaluation (1) HIV and (2) diabetes. Reaction times to pair asthma with positive or negative word stimuli in the three IATs were compared in a repeated measure ANOVA. Furthermore, the relationship between affective evaluation, self-reported asthma-specific coping, and negative affect was explored., Results: Individuals reporting an asthma diagnosis showed a stronger negative evaluation of asthma than healthy individuals in the ST-IAT. This negative evaluation was positively related to the self-report of dysfunctional coping strategies. However, in the IAT introducing a downward social comparison with HIV, evaluation of asthma was less negative and no longer positively related to the report of dysfunctional coping., Conclusion: Downward social comparison can buffer against negative affective evaluation of asthma. The context dependency of illness-related attitudes requires attention in future research and asthma management practice.

A proposed mechanism for magnetic compasses in animals is that systems of radical pairs transduce magnetic field information to the nervous system. One can show that perfectly ordered arrays of radical pairs are sensitive to the direction of the external magnetic field and can thus operate, in principle, as a magnetic compass. Here, we investigate how disorder, inherent in biological cells, affects the ability of radical pair systems to provide directional information. We consider biologically inspired geometrical arrangements of ensembles of radical pairs with increasing amounts of disorder and calculate the effect of changing the direction of the external magnetic field on the rate of chemical signal production by radical pair systems. Using a previously established signal transduction model, we estimate the minimum number of receptors necessary to allow for detection of the change in chemical signal owing to changes in magnetic field direction. We quantify the required increase in the number of receptors to compensate for the signal attenuation through increased disorder. We find radical-pair-based compass systems to be relatively robust against disorder, suggesting several scenarios as to how a compass structure can be realized in a biological cell.

The sensory basis of magnetoreception in animals still remains a mystery. One hypothesis of magnetoreception is that photochemical radical pair reactions can transduce magnetic information in specialized photoreceptor cells, possibly involving the photoreceptor molecule cryptochrome. This hypothesis triggered a considerable amount of research in the past decade. Here, we present an updated picture of the radical-pair photoreceptor hypothesis. In our review, we will focus on insights that can assist biologists in their search for the elusive magnetoreceptors.

Considerable individual differences exist in asthma patients' airway responses to emotional stimuli, but little is known about the generalization of such responses across situations or states of airways constriction. Fifty-four asthma patients and 25 healthy controls viewed in two separate sessions, films and blocks of pictures from each of three emotional qualities, pleasant, unpleasant, and neutral. At the beginning of each session, patients received a placebo or anti-cholinergic bronchodilator (ipratropium bromide), respectively, in a randomized double-blind design. Respiratory resistance, reactance and impedance were recorded throughout stimulus presentations with impulse oscillometry. Resistance increases showed a moderate degree of generalization across unpleasant films and pictures, unpleasant and pleasant pictures, as well as cholinergic blockade and placebo. Thus, the intensity of airway responses to unpleasant emotional stimuli is a moderately stable characteristic of asthma patients. In addition to the central airway, peripheral and extrathoracic airways may also contribute the consistency of such responses., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Blood-injection-injury (BII) phobia patients sometimes faint during exposure to relevant stimuli. However, mechanisms and timing of physiological adjustments in BII phobia remain poorly understood. In a larger sample of 60 patients and 20 controls, we sought to replicate findings of a prior study demonstrating the role of hyperventilation in the phobic response. We also investigated the timing of respiratory adjustment across an extended exposure recovery period. In addition, because intense disgust is commonly reported by patients, responses to surgery films were compared to a pure disgust film. End-tidal PCO(2) dropped significantly while volume and flow increased during the surgery film in patients compared to controls and to other emotional films except disgust. Patients recovered quickly following the disgust film but not the surgery film. PCO(2), volume, and flow parameters showed robust associations with anxiety, disgust, and physical symptoms. Findings suggest that respiratory adjustments during and after phobic exposure may provide a critical missing link in the understanding of the psychophysiology of this singular disorder, including why fainting often occurs after the stimulus is removed., (Copyright © 2010 Elsevier B.V. All rights reserved.)

It was recently discovered that the photoreceptor cryptochrome is involved in mediating magnetosensitive entrainment of the internal clock of fruit flies.1 This discovery follows other recent studies implicating a role of cryptochrome in mediating magnetic sensitivity in orientation responses of fruit flies2,3 and growth responses of plants.4 Such widespread use of the same molecule for mediating magnetic sensitivity might suggest that cryptochrome is in some way optimal for detecting the magnetic field of the earth and that the magnetoreception function cannot be easily taken over by other molecules. This raises the question what properties might set cryptochromes apart from other molecules in terms of their ability to detect the geomagnetic field. Here, we will discuss possible answers to this question. We will first review the likely biophysical mechanism by which magnetic fields can be detected by a photoreceptor and discuss what constitutes an optimal photo-magneto-receptor. We will then discuss in how far cryptochrome matches the profile of an optimal molecule and what further steps are required for more conclusive answers.