Nyborgkromann5552

Carbon dioxide (CO2) movement across cellular membranes is passive and governed by Fick's law of diffusion. Until recently, we believed that gases cross biological membranes exclusively by dissolving in and then diffusing through membrane lipid. However, the observation that some membranes are CO2 impermeable led to the discovery of a gas molecule moving through a channel; namely, CO2 diffusion through aquaporin-1 (AQP1). Later work demonstrated CO2 diffusion through rhesus (Rh) proteins and NH3 diffusion through both AQPs and Rh proteins. The tetrameric AQPs exhibit differential selectivity for CO2 versus NH3 versus H2O, reflecting physico-chemical differences among the small molecules as well as among the hydrophilic monomeric pores and hydrophobic central pores of various AQPs. Preliminary work suggests that NH3 moves through the monomeric pores of AQP1, whereas CO2 moves through both monomeric and central pores. Initial work on AQP5 indicates that it is possible to create a metal-binding site on the central pore's extracellular face, thereby blocking CO2 movement. The trimeric Rh proteins have monomers with hydrophilic pores surrounding a hydrophobic central pore. Preliminary work on the bacterial Rh homologue AmtB suggests that gas can diffuse through the central pore and three sets of interfacial clefts between monomers. Finally, initial work indicates that CO2 diffuses through the electrogenic Na/HCO3 cotransporter NBCe1. At least in some cells, CO2-permeable proteins could provide important pathways for transmembrane CO2 movements. Such pathways could be amenable to cellular regulation and could become valuable drug targets.Many insects can detect carbon dioxide (CO2) plumes using a conserved receptor made up of members of the gustatory receptor (Gr) family Gr1, Gr2 and Gr3. Mosquitoes are attracted to host animals for blood meals using plumes of CO2 in the exhaled breath using the receptor expressed in the A neuron of the capitate peg sensilla type on the maxillary palps. The receptor is known to also detect several other classes of odorants, including ones emitted from human skin. Here, we discover that a common skin odorant, butyric acid, can cause a phasic activation followed by an unusually prolonged tonic activity after the stimulus is over in the CO2 neurons of mosquitoes. The effect is conserved in both Aedes aegypti and Anopheles gambiae mosquitoes. This raises a question about its role in a mosquito's preference for the skin odour of different individuals. Butyric acid belongs to a small number of odorants known to cause the prolonged activation of the CO2 receptor. A chemical informatic analysis identifies a specific set of physico-chemical features that can be used in a machine learning predictive model for the prolonged activators. Interestingly, this set is different from physico-chemical features selected for activators or inhibitors, indicating that each has a distinct structural basis. The structural understanding opens up an opportunity to find novel ligands to manipulate the CO2 receptor and mosquito behaviour.Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases and is associated with increased risk of death. Recent studies have shown that hypercapnia inhibits expression of select innate immune genes and suppresses host defence against bacterial and viral pneumonia in mice. In the current study, we evaluated the effect of culture under conditions of hypercapnia (20% CO2) versus normocapnia (5% CO2), both with normoxia, on global gene transcription in human THP-1 and mouse RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We found that hypercapnia selectively downregulated transcription of LPS-induced genes associated with innate immunity, antiviral response, type I interferon signalling, cytokine signalling and other inflammatory pathways in both human and mouse macrophages. Simultaneously, hypercapnia increased expression of LPS-downregulated genes associated with mitosis, DNA replication and DNA repair. These CO2-induced changes in macrophage gene expression help explain hypercapnic suppression of antibacterial and antiviral host defence in mice and reveal a mechanism that may underlie, at least in part, the high mortality of patients with severe lung disease and hypercapnia.In plants, stomata control water loss and CO2 uptake. The aperture and density of stomatal pores, and hence the exchange of gases between the plant and the atmosphere, are controlled by internal factors such as the plant hormone abscisic acid (ABA) and external signals including light and CO2. Selleck Pracinostat In this study, we examine the importance of ABA catabolism in the stomatal responses to CO2 and light. By using the ABA 8'-hydroxylase-deficient Arabidopsis thaliana double mutant cyp707a1 cyp707a3, which is unable to break down and instead accumulates high levels of ABA, we reveal the importance of the control of ABA concentration in mediating stomatal responses to CO2 and light. Intriguingly, our experiments suggest that endogenously produced ABA is unable to close stomata in the absence of CO2. Furthermore, we show that when plants are grown in short day conditions ABA breakdown is required for the modulation of both elevated [CO2]-induced stomatal closure and elevated [CO2]-induced reductions in leaf stomatal density. ABA catabolism is also required for the stomatal density response to light intensity, and for the full range of light-induced stomatal opening, suggesting that ABA catabolism is critical for the integration of stomatal responses to a range of environmental stimuli.Soluble adenylyl cyclase (sAC; ADCY10) is a bicarbonate (HCO3 -)-regulated enzyme responsible for the generation of cyclic adenosine monophosphate (cAMP). sAC is distributed throughout the cell and within organelles and, as such, plays a role in numerous cellular signalling pathways. Carbonic anhydrases (CAs) nearly instantaneously equilibrate HCO3 -, protons and carbon dioxide (CO2); because of the ubiquitous presence of CAs within cells, HCO3 --regulated sAC can respond to changes in any of these factors. Thus, sAC can function as a physiological HCO3 -/CO2/pH sensor. Here, we outline examples where we have shown that sAC responds to changes in HCO3 -, CO2 or pH to regulate diverse physiological functions.