Effects of mesophyll conductance on vegetation responses to elevated CO2 concentrations in a land surface model.

Mesophyll conductance (gm ) is known to affect plant photosynthesis. However, gm is rarely explicitly considered in land surface models (LSMs), with the consequence that its role in ecosystem and large-scale carbon and water fluxes is poorly understood. In particular, the different magnitudes of gm across plant functional types (PFTs) are expected to cause spatially divergent vegetation responses to elevated CO2 concentrations. Here, an extensive literature compilation of gm across major vegetation types is used to parameterize an empirical model of gm in the LSM JSBACH and to adjust photosynthetic parameters based on simulated An  - Ci curves. We demonstrate that an explicit representation of gm changes the response of photosynthesis to environmental factors, which cannot be entirely compensated by adjusting photosynthetic parameters. These altered responses lead to changes in the photosynthetic sensitivity to atmospheric CO2 concentrations which depend both on the magnitude of gm and the climatic conditions, particularly temperature. We then conducted simulations under ambient and elevated (ambient + 200 µmol/mol) CO2 concentrations for contrasting ecosystems and for historical and anticipated future climate conditions (representative concentration pathways; RCPs) globally. The gm -explicit simulations using the RCP8.5 scenario resulted in significantly higher increases in gross primary productivity (GPP) in high latitudes (+10% to + 25%), intermediate increases in temperate regions (+5% to + 15%), and slightly lower to moderately higher responses in tropical regions (-2% to +5%), which summed up to moderate GPP increases globally. Similar patterns were found for transpiration, but with a lower magnitude. Our results suggest that the effect of an explicit representation of gm is most important for simulated carbon and water fluxes in the boreal zone, where a cold climate coincides with evergreen vegetation.

CO2 -Induced Morphological Transition of Co-Assemblies from Block-Random Segmented Polymers.

The co-assembly process is an effective approach to construct hierarchically nanostructured soft materials, but morphological transition of co-assemblies upon external stimuli, particularly the "green" trigger CO2 , is not unraveled yet. Here, a segmented copolymer, poly(styrene)-block-poly[(4-vinyl pyridine)-random-((2-(diethylamino)ethyl methacrylate)] (P1), is used to co-assemble in the mixed solvent of dimethyl formamide and water with poly(ethylene oxide)-block-poly[(4-vinyl pyridine)-random-((2-(diethylamino)ethyl methacrylate)] (P2) and poly(ethylene oxide)-block-poly(acrylic acid) (P3), respectively. It is found that Janus micelles are generated from the P1-P2 pair in the presence of ferric ion, while wormlike micelles are formed from the P1-P3 duad. Upon stimulation with CO2 , Janus and wormlike aggregates are transferred into core-shell and spherical micelles, respectively.

CO(2) rebreathing: an undergraduate laboratory to study the chemical control of breathing.

The Read CO2 rebreathing method (Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med 16: 20-32, 1967) provides a simple and reproducible approach for studying the chemical control of breathing. It has been widely used since the modifications made by Duffin and coworkers. Our use of a rebreathing laboratory to challenge undergraduate science students to investigate the control of breathing provided 8 yr of student-generated data for comparison with the literature. Students (age: 19-22 yr, Research Ethics Board approval) rebreathed from a bag containing 5% CO2 and 95% O2 (to suppress the peripheral chemoreflex to hypoxia). Rebreathing was performed, and ventilation measured, after hyperventilation to deplete tissue CO2 stores and enable the detection of the central chemoreflex threshold. We analyzed 43 data sets, of which 10 were rejected for technical reasons. The mean threshold and ventilatory sensitivity to CO2 were 43.3 ± 3.8 mmHg and 4.60 ± 3.04 l·min(-1)·mmHg(-1) (means ± SD), respectively. Threshold values were normally distributed, whereas sensitivity was skewed to the left. Both mean values agreed well with those in the literature. We conclude that the modified rebreathing protocol is a robust method for undergraduate investigation of the chemical control of breathing.

An apnea-hypothesis of anxiety generation: Novel, respiratory, and falsifiable.

The Apnea-induced Anxiety model of Feinstein et al. continues a line of respiratory theories of panic, extending Klein's false suffocation alarm theory to a broader range of fear and anxiety states. It draws on neurobiological evidence including the underappreciated role of the amygdala in eliciting periods of apnea and CO2 tolerance. Further progress can be expected from empirical testing and integration with neuromodulatory systems that support respiration, activity, fear and anxiety, in particular the orexin system.

Insights Into Cerebral Tissue-Specific Response to Respiratory Challenges at 7T: Evidence for Combined Blood Flow and CO2-Mediated Effects.

Cerebrovascular reactivity (CVR) mapping is finding increasing clinical applications as a non-invasive probe for vascular health. Further analysis extracting temporal delay information from the CVR response provide additional insight that reflect arterial transit time, blood redistribution, and vascular response speed. Untangling these factors can help better understand the (patho)physiology and improve diagnosis/prognosis associated with vascular impairments. Here, we use hypercapnic (HC) and hyperoxic (HO) challenges to gather insight about factors driving temporal delays between gray-matter (GM) and white-matter (WM). Blood Oxygen Level Dependent (BOLD) datasets were acquired at 7T in nine healthy subjects throughout BLOCK- and RAMP-HC paradigms. In a subset of seven participants, a combined HC+HO block, referred as the "BOOST" protocol, was also acquired. Tissue-based differences in Rapid Interpolation at Progressive Time Delays (RIPTiDe) were compared across stimulus to explore dynamic (BLOCK-HC) versus progressive (RAMP-HC) changes in CO2, as well as the effect of bolus arrival time on CVR delays (BLOCK-HC versus BOOST). While GM delays were similar between the BLOCK- (21.80 ± 10.17 s) and RAMP-HC (24.29 ± 14.64 s), longer WM lag times were observed during the RAMP-HC (42.66 ± 17.79 s), compared to the BLOCK-HC (34.15 ± 10.72 s), suggesting that the progressive stimulus may predispose WM vasculature to longer delays due to the smaller arterial content of CO2 delivered to WM tissues, which in turn, decreases intravascular CO2 gradients modulating CO2 diffusion into WM tissues. This was supported by a maintained ∼10 s offset in GM (11.66 ± 9.54 s) versus WM (21.40 ± 11.17 s) BOOST-delays with respect to the BLOCK-HC, suggesting that the vasoactive effect of CO2 remains constant and that shortening of BOOST delays was be driven by blood arrival reflected through the non-vasodilatory HO contrast. These findings support that differences in temporal and magnitude aspects of CVR between vascular networks reflect a component of CO2 sensitivity, in addition to redistribution and steal blood flow effects. Moreover, these results emphasize that the addition of a BOOST paradigm may provide clinical insights into whether vascular diseases causing changes in CVR do so by way of severe blood flow redistribution effects, alterations in vascular properties associated with CO2 diffusion, or changes in blood arrival time.

The Implications of the Diving Response in Reducing Panic Symptoms.

Increased CO2 sensitivity is common in panic disorder (PD) patients. Free divers who are known for their exceptional breathing control have lower CO2 sensitivity due to training effects. This study aimed to investigate the immediate effects of cold facial immersion (CFI), breath holding and CO2 challenges on panic symptoms. Healthy participants and patients with PD were subjected to four experimental conditions in a randomly assigned order. The four conditions were (a) breath-holding (BH), (b) CFI for 30 s, (c) CO2 challenge, and (d) CO2 challenge followed by CFI. Participants completed a battery of psychological measures, and physiological data (heart rate and respiration rate) were collected following each experimental condition. Participants with PD were unable to hold their breath for as long as normal controls; however, this finding was not significant, potentially due to a small sample size. Significant reductions in both physiological and cognitive symptoms of panic were noted in the clinical group following the CFI task. As hypothesized, the CFI task exerted demonstrable anxiolytic effects in the clinical group in this study by reducing heart rate significantly and lessening self-reported symptoms of anxiety and panic. This outcome demonstrates the promise of the CFI task for clinical applications.

Effects of sex differences on breath-hold diving performance.

PURPOSE: The present study aimed to measure diving response, CO2 sensitivity and forced vital capacity in male and female breath-hold divers (BHDs), and to determine their effect on breath-hold diving performance. METHODS: This study included 8 non-divers (NDs, 4 males and 4 females) and 15 BHDs (7 males and 8 females). For NDs, diving response was measured during breath-holding with facial immersion, whereas for BHDs CO2 sensitivity was also measured. RESULTS: Compared to NDs, BHDs showed a prominent diving response. In BHDs, no statistically significant sex differences were observed in diving response and CO2 sensitivity. Furthermore, a positive correlation was found between performance and the % forced vital capacity in BHDs. CONCLUSION: It was suggested that % forced vital capacity contributed more significantly to performance than diving response and CO2 sensitivity. Furthermore, the higher performance of male divers compared to female divers may be due to the % forced vital capacity rather than the diving response and CO2 sensitivity.

Diblock, Triblock and Cyclic Amphiphilic Copolymers with CO2 Switchability: Effects of Topology.

The combination of topology and CO2 switchability could provide new options for amphiphilic copolymers. Cyclic molecules supply novel topologies, and CO2 switching provides stimulus responsiveness. Cyclic poly(2-(diethylamino)ethyl methacrylate)-b-poly(ethylene oxide) and their corresponding block copolymers were prepared from poly(ethylene oxide) and 2-(diethylamino)ethyl methacrylate via atom transfer radical polymerization and Keck allylation with a Hoveyda-Grubbs catalyst. Changes in conductivity, surface activity, and hydrodynamic size were examined to illustrate the switchability of the produced amphiphilic copolymers upon contact with CO2 in the presence of water. The reversible emulsification and switchable viscosity behaviors of the copolymers were also demonstrated.

High Behavioral Sensitivity to Carbon Dioxide Associates with Enhanced Fear Memory and Altered Forebrain Neuronal Activation.

There is considerable interest in pre-trauma individual differences that may contribute to increased risk for developing post-traumatic stress disorder (PTSD). Identification of underlying vulnerability factors that predict differential responses to traumatic experiences is important. Recently, the relevance of homeostatic perturbations in shaping long-term behavior has been recognized. Sensitivity to CO2 inhalation, a homeostatic threat to survival, was shown to associate with the later development of PTSD symptoms in veterans. Here, we investigated whether behavioral sensitivity to CO2 associates with PTSD-relevant behaviors and alters forebrain fear circuitry in mice. Mice were exposed to 5% CO2 or air inhalation and tested one week later on acoustic startle and footshock contextual fear conditioning, extinction and reinstatement. CO2 inhalation evoked heterogenous freezing behaviors (high freezing CO2-H and low freezing CO2-L) that significantly associated with fear conditioning and extinction behaviors. CO2-H mice elicited potentiated conditioned fear and delayed extinction while behavioral responses in CO2-L mice were similar to the air group. Persistent neuronal activation marker ΔFosB immunostaining revealed altered regional neuronal activation within the hippocampus, amygdala and medial pre-frontal cortex that correlated with conditioned fear and extinction. Inter-regional co-activation mapping revealed disruptions in the coordinated activity of hippocampal dentate-amygdala-infralimbic regions and infralimbic-prelimbic associations in CO2-H mice that may explain their enhanced fear phenotype. In conclusion, our data support an association of behavioral sensitivity to interoceptive threats such as CO2 with altered fear responding to exteroceptive threats and suggest that "CO2-sensitive" individuals may be susceptible to developing PTSD.

A neurobiological framework of separation anxiety and related phenotypes.

In the DSM-5, separation anxiety disorder (SAD) is newly classified in the chapter on anxiety, renewing research efforts into its etiology. In this narrative review, we summarize the current literature on the genetic, endocrine, physiological, neural and neuropsychological underpinnings of SAD per se, SAD in the context of panic disorder, separation anxiety symptoms, and related intermediate phenotypes. SAD aggregates in families and has a heritability of ~43%. Variants in the oxytocin receptor, serotonin transporter, opioid receptor µ1, dopamine D4 receptor and translocator protein genes have all been associated with SAD. Dysregulation of the hypothalamus-pituitary-adrenal axis, dysfunctional cortico-limbic interaction and biased cognitive processing seem to constitute further neurobiological markers of separation anxiety. Hypersensitivity to carbon dioxide appears to be an endophenotype shared by SAD, panic disorder and anxiety sensitivity. The identification of biological risk markers and its multi-level integration hold great promise regarding the prediction of SAD risk, maintenance and course, and in the future may allow for the selection of indicated preventive and innovative, personalized therapeutic interventions.

Reappraising Preclinical Models of Separation Anxiety Disorder, Panic Disorder, and CO2 Sensitivity: Implications for Methodology and Translation into New Treatments.

Separation anxiety applies to multiple forms of distress responses seen in mammals during postnatal development, including separation from a caregiver. Childhood separation anxiety disorder is an important risk factor for developing panic disorder in early adulthood, and both conditions display an increased sensitivity to elevated CO2 concentrations inhaled from the air. By interfacing epidemiological, genetic, and physiological knowledge with preclinical animal research models, it is possible to decipher the mechanisms that are central to separation anxiety and panic disorders while also suggesting possible therapies. Preclinical research models allow for environmentally controlled studies of early interferences with parental care. These models have shown that different forms of early maternal separation in mice and rats induce elevated CO2 respiratory sensitivity, an important biomarker of separation anxiety and panic disorders. In mice, this is likely due to gene-environment interactions that affect multiple behavioural and physical phenotypes after exposure to this early adversity. Although several questions regarding the causal mechanism of separation anxiety and panic disorder remain unanswered, the identification and improved understanding of biomarkers that link these mental health conditions under the guise of preclinical research models in conjunction with human longitudinal cohort studies can help resolve these issues.

Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats.

Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine ß hydroxylase (DßH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2-chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2-evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2-evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2-positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal gray (VLPAG) subdivision in CO2-sensitive strains. Conversely, DßH-positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders.

New dimensions in the use of rodent behavioral tests for novel drug discovery and development.

INTRODUCTION: Dimensional models of psychopathology describe mental illness in terms of natural variance along certain phenotypic dimensions that are continuous with normal. Vulnerability to psychopathology might arise when certain adaptive psychophysiological processes, conserved between humans and non-human animals, function outside of their "normal" range. Therefore, an in-depth understanding of the neurobiology and neurochemistry underlying these processes could identify possible novel drug targets. AREAS COVERED: Psychophysiological processes that might be related to anxiety disorders and depression are proposed and discussed. Those processes relevant to depressive disorders include: hedonic responsiveness, biases in the processing of stimuli, and sleep architecture. Those relevant to anxiety disorders include: startle reactivity, CO2 sensitivity, and fear generalization. Rodent behavioral tests for assessing the function of these processes and investigating their neurobiology are described. A psychophysiological process strategy for translational research is proposed, which focusses on understanding the neurobiology and neurochemistry underlying key psychophysiological processes that, when their activity deviates from normal, are associated with neuropsychiatric symptoms. This strategy emphasizes the use of analogous tests and measures in both preclinical and clinical studies, while de-emphasizing the use of preclinical animal models that attempt to replicate features of the neuropsychiatric disorder through experimental manipulations. EXPERT OPINION: Investigating the neurobiology of key psychophysiological processes in rodents should enhance our understanding of the pathophysiology of neuropsychiatric disorders. New drug development could be directed toward developing pharmacological strategies that would normalize the function of these psychophysiological processes.

Effects of changes in atmospheric carbon dioxide on the location of hosts by the moth, Cactoblastis cactorum.

Sensory organs that detect CO2 are common in herbivorous moths and butterflies, but their function has been unclear until now. As the CO2 gradients in the vicinity of a host plant depend on its physiological condition, CO2 could provide a sensory cue for the suitability of the plant as a larval food source. This study investigated whether changing the atmospheric CO2 concentration affected oviposition by Cactoblastis cactorum on its host, the cactus Opuntia stricta. On host plants exposed to rapid fluctuations in CO2 concentration, the frequency of oviposition was reduced by a factor of 3.2 compared to the control. As the fluctuations mask the much smaller CO2 signals generated by the plants, this suggests that those signals constitute an important component of the host identification process. On host plants exposed to a constant background of doubled CO2, oviposition was also reduced, by a factor of 1.8. An increased background reduces host signal detectability, partially as a consequence of a general principle of sensory physiology (Weber-Fechner's law), and partially due to other factors specific to CO2-receptor neurons.