27 research outputs found

    Roles and mechanisms of action of the L-cysteine cystathionine-gamma-lyase hydrogen sulphide pathway in the heart

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    Hydrogen sulphide (H2S) is a naturally occurring gas and originally the primary focus of research was to investigate its toxicity. In 1989 a physiological role of H2S was proposed after endogenous levels were detected in the rat brain and normal human post-mortem tissue. This discovery has led to an explosion of interest in H2S as a biological mediator. Identification of H2S synthesising enzymes in the cardiovascular system has led to a number of studies examining specific regulatory actions of H2S. The hypothesis underlying the studies in this thesis was that H2S synthesising enzymes exist in the myocardium and the resulting H2S provides cardioprotection against ischaemia-reperfusion injury. This was investigated using a broad range of experimental techniques including Langendorff isolated perfused rat heart models, biochemical H2S stimulation and detection assays, PCR, and Western blotting. The principal findings can be summarised as follows: 1. Rat myocardium has the potential to express both CSE and CBS H2S synthesising enzymes, due to the confirmed detection of mRNA. 2. Furthermore it was possible to exogenously stimulate the CSE enzyme, with its substrate L-cysteine, to produce H2S gas which limited infarct size during regional ischaemia-reperfusion. 3. Endogenous H2S levels were up-regulated during ischaemia-reperfusion, consistent with an endogenous protective role within the myocardium. 4. Simple and complex H2S/thiol containing compounds produced cardioprotection during regional ischaemia-reperfusion, with a mechanism that involves PI3k and Akt activation, implicating recruitment of downstream kinases within the RISK pathway. The studies presented have provided a significant advancement in understanding the involvement of H 2S in cardioprotection during ischaemia-reperfusion. It has also raised questions such as the exact mechanism of action of H2S donor/thiol containing compounds and highlighted the need for more robust H2S donors. The scope for H2S as an endogenous mediator also stems beyond that of cardioprotection, as the range of body systems and cell types are continually expanding

    Scaling of axial muscle architecture in juvenile Alligator mississippiensis reveals an enhanced performance capacity of accessory breathing mechanisms

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    From Wiley via Jisc Publications RouterHistory: received 2020-11-16, rev-recd 2021-07-08, accepted 2021-07-12, pub-electronic 2021-07-23Article version: VoRPublication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/I021116/1Funder: National Science Foundation; Id: http://dx.doi.org/10.13039/100000001; Grant(s): 17565187Abstract: Quantitative functional anatomy of amniote thoracic and abdominal regions is crucial to understanding constraints on and adaptations for facilitating simultaneous breathing and locomotion. Crocodilians have diverse locomotor modes and variable breathing mechanics facilitated by basal and derived (accessory) muscles. However, the inherent flexibility of these systems is not well studied, and the functional specialisation of the crocodilian trunk is yet to be investigated. Increases in body size and trunk stiffness would be expected to cause a disproportionate increase in muscle force demands and therefore constrain the basal costal aspiration mechanism, necessitating changes in respiratory mechanics. Here, we describe the anatomy of the trunk muscles, their properties that determine muscle performance (mass, length and physiological cross‐sectional area [PCSA]) and investigate their scaling in juvenile Alligator mississippiensis spanning an order of magnitude in body mass (359 g–5.5 kg). Comparatively, the expiratory muscles (transversus abdominis, rectus abdominis, iliocostalis), which compress the trunk, have greater relative PCSA being specialised for greater force‐generating capacity, while the inspiratory muscles (diaphragmaticus, truncocaudalis ischiotruncus, ischiopubis), which create negative internal pressure, have greater relative fascicle lengths, being adapted for greater working range and contraction velocity. Fascicle lengths of the accessory diaphragmaticus scaled with positive allometry in the alligators examined, enhancing contractile capacity, in line with this muscle's ability to modulate both tidal volume and breathing frequency in response to energetic demand during terrestrial locomotion. The iliocostalis, an accessory expiratory muscle, also demonstrated positive allometry in fascicle lengths and mass. All accessory muscles of the infrapubic abdominal wall demonstrated positive allometry in PCSA, which would enhance their force‐generating capacity. Conversely, the basal tetrapod expiratory pump (transversus abdominis) scaled isometrically, which may indicate a decreased reliance on this muscle with ontogeny. Collectively, these findings would support existing anecdotal evidence that crocodilians shift their breathing mechanics as they increase in size. Furthermore, the functional specialisation of the diaphragmaticus and compliance of the body wall in the lumbar region against which it works may contribute to low‐cost breathing in crocodilians

    Water vapour self-continuum in near-visible IR absorption bands: Measurements and semiempirical model of water dimer absorption

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    The nature of the water vapour continuum has been of great scientific interest for more than 60 years. Here, water vapour self-continuum absorption spectra are retrieved at temperatures of 398 K and 431 K and at vapour pressures from 1000 to 4155 mbar in the 8800 and 10,600 cm−1 absorption bands using high-resolution FTS measurements. For the observed conditions, the MT_CKD-3.2 model underestimates the observed continuum on average by 1.5–2 times. We use the hypothesis that water dimers contribute to the continuum absorption to simulate the experimentally-retrieved self-continuum absorption spectra, and to explain their characteristic temperature dependence and spectral behaviour. The values of the effective equilibrium constant are derived for the observed temperatures. We find that the dimer-based model fits well to the measured self-continuum from this and previous studies, but requires a higher effective equilibrium constant compared to the modern estimates within the temperature range (268–431 K) and spectral region studied. It is shown that water dimers are likely responsible for up to 50% of the observed continuum within these bands. Possible causes of the incomplete explanation of the continuum are discussed. Extrapolating these measurements to atmospheric temperatures using the dimer-based model, we find that the newly-derived self-continuum reduces calculated surface irradiances by 0.016 W m−2 more than the MT_CKD-3.2 self-continuum in the 8800 cm−1 band for overhead-Sun mid-latitude summer conditions, corresponding to a 12.5% enhancement of the self-continuum radiative effect. The change integrated across the 10,600 cm−1 band is about 1%, but with significan

    Cross-sections for heavy atmospheres:H<sub>2</sub>O continuum

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    Most of the exoplanets detected up to now transit in front of their host stars, allowing for the generation of transmission spectra; the study of exoplanet atmospheres relies heavily upon accurate analysis of these spectra. Recent discoveries mean that the study of atmospheric signals from low-mass, temperate worlds are becoming increasingly common. The observed transit depth in these planets is small and more difficult to analyze. Analysis of simulated transmission spectra for two small, temperate planets (GJ 1214 b and K2-18 b) is presented, giving evidence for significant differences in simulated transit depth when the water vapor continuum is accounted for when compared to models omitting it. These models use cross-sections from the CAVIAR lab experiment for the water self-continuum up to 10,000 cm1^{-1}; these cross-sections exhibit an inverse relationship with temperature, hence lower-temperature atmospheres are the most significantly impacted. Including the water continuum strongly affects transit depths, increasing values by up to 80 ppm, with the differences for both planets being detectable with the future space missions Ariel and JWST. It is imperative that models of exoplanet spectra move toward adaptive cross-sections, increasingly optimized for H2_2O-rich atmospheres. This necessitates including absorption contribution from the water vapor continuum into atmospheric simulations

    Cross-sections for heavy atmospheres:H<sub>2</sub>O continuum

    No full text
    Most of the exoplanets detected up to now transit in front of their host stars, allowing for the generation of transmission spectra; the study of exoplanet atmospheres relies heavily upon accurate analysis of these spectra. Recent discoveries mean that the study of atmospheric signals from low-mass, temperate worlds are becoming increasingly common. The observed transit depth in these planets is small and more difficult to analyze. Analysis of simulated transmission spectra for two small, temperate planets (GJ 1214 b and K2-18 b) is presented, giving evidence for significant differences in simulated transit depth when the water vapor continuum is accounted for when compared to models omitting it. These models use cross-sections from the CAVIAR lab experiment for the water self-continuum up to 10,000 cm−1 ; these cross-sections exhibit an inverse relationship with temperature, hence lower-temperature atmospheres are the most significantly impacted. Including the water continuum strongly affects transit depths, increasing values by up to 60 ppm, with the differences for both planets being detectable with the future space missions Ariel and JWST. It is imperative that models of exoplanet spectra move toward adaptive cross-sections, increasingly optimized for H2O-rich atmospheres. This necessitates including absorption contribution from the water vapor continuum into atmospheric simulations
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