Biology subjects

St John Smith, E.

Publications and source records attributed to St John Smith, E..

3 recordsLinked to original sources

bioRxiv2020

Photoacoustics resolves species-specific differences in haemoglobin concentration and oxygenation

Introduction Photoacoustic imaging (PAI) enables the detection of blood haemoglobin (HB) concentration and oxygenation (SO2) with high contrast and resolution. To date, the relationship between photoacoustically determined total Haemoglobin (THbMSOT) and oxygen saturation (SO2) biomarkers and the underlying biochemical blood parameters has yet to be established. We sought to explore these relationships in a species-specific manner.Methods Experiments were performed in vitro using tissue-mimicking agar phantoms. Blood was extracted from mouse, rat, human and naked mole-rat (Heterocephalus glaber), anticoagulated in EDTA and measured within 48 hours. THbMSOT and SO2MSOT were measured using a commercial photoacoustic tomography system (InVision 128, iThera Medical GmBH). Biochemical blood parameters such as haemoglobin concentration (HB, g/dL), haematocrit (HCT, %) and red blood cell count (RBC, μL-1) were assessed using a haematology analyser (Mythic 18 Vet, Woodley Equipment).Results A significant correlation was observed between THbMSOT and biochemical HB, HCT and RBC in mouse and rat blood. Moreover, PAI accurately recapitulated inter-species variations in HB and HCT between mouse and rat blood and resolved differences in the oxygen dissociation curves between human, mouse and rat. With these validation data in hand, we applied PAI to studies of blood obtained from naked mole-rats and could confirm the high oxygen affinity of this species in comparison to other rodents of similar size.Conclusion In summary, our results demonstrate the high sensitivity of photoacoustically determined biomarkers towards species-specific variations in vitro.Competing Interest StatementJB, IQG and SEB have previously received research support from iThera Medical GmbH and Cyberdyne Inc.View Full Text

bioengineering↗

bioRxiv2020

Cholesterol rich, highly phase separated, naked mole-rat brain lipids are exquisitely sensitive to amyloid induced membrane damage

Naked mole-rats are extraordinarily long-lived rodents that do not develop age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta peptide, even from a young age Therefore, these animals offer an opportunity to investigate mechanisms of resistance against the neurotoxicity of amyloid beta aggregation. Working in this direction, here we examine the composition, phase behaviour, and amyloid beta interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with metabolism of ceramides, sphingomyelin and ceramide receptor activity were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase occupying up to 80% of the supported lipid bilayer. These observations are consistent with the membrane pacemaker hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. However, we found that exposure to amyloid beta disrupts the naked mole-rat brain lipid membranes while those formed from mouse brain lipids exhibit small, well-defined footprints, whereby the amyloid beta penetrates deeply into the lipid membranes. These results suggest that in naked mole-rats the lipid composition of cell membranes may offer neuroprotection through resistance to oxidative processes rather than through mechanical effects.

biophysics↗

bioRxiv2018

Human labor pain is influenced by the voltage-gated potassium channel KV6.4 subunit

AO_SCPLOWBSTRACTC_SCPLOWWe sought genetic effects on labour pain by studying healthy women who did not request analgesia during their first delivery. Extensive sensory and psychometric testing were normal in these women, except for significantly higher cuff-pressure pain. We found an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 exerts a dominant negative effect and cannot modulate the voltage-dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, we observed Kcng4 (KV6.4) expression in 40% of retrograde labelled mouse uterine sensory neurones, all of which expressed KV2.1, and over 90% expressed nociceptor genes Trpv1 and Scn10a. In neurones overexpressing KV6.4-Met419, the voltage-dependence of inactivation for KV2.1 is more depolarised compared to neurones overexpressing KV6.4. Finally, KV6.4-Met419 overexpressing neurones have a higher action potential threshold. We conclude KV6.4 can influence human labour pain by modulating the excitability of uterine nociceptors.

neuroscience↗