Sniffing out urinary tract infection—diagnosis based on volatile organic compounds and smell profile

Current available methods for the clinical diagnosis of urinary tract infection (UTI) rely on a urine dipstick test or culturing of pathogens. The dipstick test is rapid (available in 1–2 min), but has a low positive predictive value, while culturing is time-consuming and delays diagnosis (24–72 h between sample collection and pathogen identification). Due to this delay, broad-spectrum antibiotics are often prescribed immediately. The over-prescription of antibiotics should be limited, in order to prevent the development of antimicrobial resistance. As a result, there is a growing need for alternative diagnostic tools. This paper reviews applications of chemical-analysis instruments, such as gas chromatography–mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), field asymmetric ion mobility spectrometry (FAIMS) and electronic noses (eNoses) used for the diagnosis of UTI. These methods analyse volatile organic compounds (VOCs) that emanate from the headspace of collected urine samples to identify the bacterial pathogen and even determine the causative agent’s resistance to different antibiotics. There is great potential for these technologies to gain wide-spread and routine use in clinical settings, since the analysis can be automated, and test results can be available within minutes after sample collection. This could significantly reduce the necessity to prescribe broad-spectrum antibiotics and allow the faster and more effective use of narrow-spectrum antibiotics

Channel-mediated ATP release in the nervous system

ATP is well established as a transmitter and modulator in the peripheral and central nervous system. While conventional exocytotic release of ATP at synapses occurs, this transmitter is unusual in also being released into the extracellular space via large-pored plasma membrane channels. This review considers the channels that are known to be permeable to ATP and some of the functions of channel-mediated ATP release. While the possibility of ATP release via channels mediating volume transmission has been known for some time, localised ATP release via channels at specialised synapses made by taste cells to the afferent nerve has recently been documented in taste buds. This raises the prospect that “channel synapses” may occur in other contexts. However, volume transmission and channel synapses are not necessarily mutually exclusive. We suggest that certain glial cells in the brain stem and hypothalamus, which possess long processes and are known to release ATP, may be candidates for both modes of ATP release -channel-mediated volume transmission in the region of their somata and more localised transmission possibly via either conventional or channel synapses from their processes at distal targets. Finally, we consider the different characteristics of vesicular and channel synapses and suggest that channel synapses may be advantageous in requiring less energy than their conventional vesicular counterparts

Structural determinants of CO2-sensitivity in the β connexin family suggested by evolutionary analysis

none8siA subclade of connexins comprising Cx26, Cx30, and Cx32 are directly sensitive to CO2. CO2 binds to a carbamylation motif present in these connexins and causes their hemichannels to open. Cx26 may contribute to CO2-dependent regulation of breathing in mammals. Here, we show that the carbamylation motif occurs in a wide range of non-mammalian vertebrates and was likely present in the ancestor of all gnathostomes. While the carbamylation motif is essential for connexin CO2-sensitivity, it is not sufficient. In Cx26 of amphibia and lungfish, an extended C-terminal tail prevents CO2-evoked hemichannel opening despite the presence of the motif. Although Cx32 has a long C-terminal tail, Cx32 hemichannels open to CO2 because the tail is conformationally restricted by the presence of proline residues. The loss of the Cterminal tail of Cx26 in amniotes was an evolutionary innovation that created a connexin hemichannel with CO2-sensing properties suitable for the regulation of breathing.noneDospinescu V.-M.; Nijjar S.; Spanos F.; Cook J.; de Wolf E.; Biscotti M.A.; Gerdol M.; Dale N.Dospinescu, V. -M.; Nijjar, S.; Spanos, F.; Cook, J.; de Wolf, E.; Biscotti, M. A.; Gerdol, M.; Dale, N