Biology subjects

Gray, C.

Publications and source records attributed to Gray, C..

22 records · Page 2Linked to original sources

bioRxiv2019

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in systemic glucose homeostasis

Bone marrow adipose tissue (BMAT) represents >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT), its role in systemic metabolism remains unclear. Using transcriptomics, we reveal that BMAT is molecularly distinct to WAT but is not enriched for brown or beige adipocyte markers. Instead, pathway analysis indicated altered glucose metabolism and decreased insulin responsiveness in BMAT. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose, including establishing a new method for BMAT identification from clinical CT scans. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake and is thus functionally distinct to WAT and BAT. However, BMAT displayed greater basal glucose uptake than axial bones or subcutaneous WAT, underscoring its potential to influence systemic glucose homeostasis. These PET/CT studies are the first to characterise BMAT function in vivo and identify BMAT as a distinct, major subtype of adipose tissue.\n\nHIGHLIGHTSO_LIBone marrow adipose tissue (BMAT) is molecularly distinct to other adipose subtypes.\nC_LIO_LIBMAT is less insulin responsive than WAT and, unlike BAT, is not cold-responsive.\nC_LIO_LIHuman BMAT has greater basal glucose uptake than axial bone or subcutaneous WAT.\nC_LIO_LIWe establish a PET/CT method for BMAT localisation and functional analysis in vivo.\nC_LI

physiology↗

bioRxiv2019

Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish

Diabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood, and currently no treatment exists to prevent these negative effects. We previously found that the NO donor sodium nitroprusside (SNP) prevents the detrimental effect of glucose on neurovascular coupling in zebrafish. We therefore sought to establish the wider effects of glucose exposure on both the neurovascular unit and on behaviour in zebrafish and the ability of SNP to prevent these.\n\nWe incubated 4 days post fertilisation (dpf) zebrafish embryos in 20mM glucose or mannitol for five days until 9dpf, with or without 0.1mM SNP co-treatment for 24h (8-9dpf), and quantified vascular nitric oxide reactivity, vascular mural cell number, expression of a klf2a reporter, glial fibrillary acidic protein (GFAP) and TRPV4, as well as spontaneous neuronal activation at 9dpf, all in the optic tectum. We also assessed the effect on light/dark preference and locomotory characteristics during free-swimming studies.\n\nWe find that glucose exposure significantly reduced nitric oxide reactivity, klf2a reporter expression, vascular mural cell number and TRPV4 expression, while significantly increasing spontaneous neuronal activation and GFAP expression (all in the optic tectum). Furthermore, when we examined larval behaviour we found glucose exposure significantly altered light/dark preference and high and low speed locomotion while in light. Co-treatment with SNP reversed all these molecular and behavioural effects of glucose exposure.\n\nOur findings comprehensively describe the negative effects of glucose exposure on the vascular anatomy, molecular phenotype, and function of the optic tectum and on whole organism behaviour. We also show that SNP or other NO donors may represent a therapeutic strategy to ameliorate the complications of diabetes on the neurovascular unit.

neuroscience↗

bioRxiv2019

crAssphage abundance and genomic selective pressure correlate with altered bacterial abundance in the fecal microbiota of South African mother-infant dyads

crAssphages are a class of bacteriophages that are highly abundant in the human gastrointestinal tract. Accordingly, crAssphage genomes have been identified in most human fecal viral metagenome studies. However, we currently have an incomplete understanding of factors impacting the transmission frequencies of these phages between mothers and infants, and the evolutionary pressures associated with such transmissions. Here, we use metagenome sequencing of stool-associated virus-like particles to identify the prevalence of crAssphage across ten South African mother-infant dyads that are discordant for HIV infection. We report the identification of a complete 97kb crAssphage genome, parts of which are detected at variable levels across each mother-infant dyad. We observed average nucleotide sequence identities of >99% for crAssphages from related mother-infant pairs but [~]97% identities between crAssphages from unrelated mothers and infants: a finding strongly suggestive of vertical mother to infant transmission. We further analyzed patterns of nucleotide diversity across the crAssphage sequences described here, identifying particularly elevated positive selection in RNA polymerase and phage tail protein encoding genes, which we validated against a crAssphage genome from previous studies. Using 16S rRNA gene sequencing, we found that the relative abundances of Bacteroides thetaiotaomicron and Parabacteroides merdae (Order: Bacteroidales) were differentially correlated with crAssphage abundance. Together, our results reveal that crAssphages may be vertically transmitted from mothers to their infants and that hotspots of selection within crAssphage RNA polymerase and phage tail protein encoding genes are potentially mediated by interactions between crAssphages and their bacterial partners.\n\nImportancecrAssphages are an ubiquitous member of the human gut microbiome and modulate interactions with key bacterial associates within the order Bacteroidales. However, the role of this interaction in the genomic evolution of crAssphage remains unclear. Across a longitudinally sampled cohort of ten South African mother-infant dyads, we use metagenome sequencing of the fecal virome and 16S rRNA gene sequencing of the fecal bacterial microbiota to elucidate the ecological and evolutionary dynamics of these interactions. Here, we demonstrate elevated levels of crAssphage average nucleotide identity between related mother-infant dyads as compared to unrelated individuals, suggesting vertical transmission. We report strong positive selection in crAssphage RNA polymerase and phage tail protein genes. Finally, we demonstrate that crAssphage abundance is linearly correlated (P < 0.014) with the abundance of two bacterial taxa, Bacteroides thetaiotaomicron and Parabacteroides merdae. These results suggest that phage-bacterial interactions may help shape ecological and evolutionary dynamics in the gut.

microbiology↗

bioRxiv2017

Designing oil palm landscapes to retain biodiversity using insights from a key ecological indicator group

Oil palm expansion threatens biodiverse ecosystems across the tropics. However, palm oil is a widely used and profitable crop, so identifying strategies that mitigate the impact of oil palm expansion on biodiversity is important. Riparian reserves (strips of forest along rivers) are protected in many countries for hydrological reasons and also support species that would not otherwise persist in oil palm. However, management guidelines for riparian zones have been informed by relatively few ecological studies. We assessed how the structural features and landscape context of riparian reserves in Sabah, Malaysia affected dung beetle communities. We also tested the use of flight intercept traps to study movement of dung beetles along linear forest corridors. Overall, dung beetle abundance in riparian reserves was 54% lower than in logged forest areas, but all species observed in the logged forest were found in at least one riparian reserve site and both species richness and diversity increased with reserve width. Distance from a large block of continuous forest affected dung beetle community composition but not species richness, abundance, or functional diversity. The amount of forest cover in the surrounding landscape improved the retention of species within riparian reserves, and increases in vegetation complexity corresponded with higher functional richness and functional dispersion. The flight intercept traps did not indicate that there is net movement of individuals out of logged forest areas into the riparian reserves. The species richness of 30 m reserves (the suggested requirement of reserves in Sabah) was only 10% lower than in logged forest, but our data indicate that riparian reserves of at least 50 - 80 m are needed for species richness and diversity to equal that in nearby logged forest. These findings, particularly if they apply more widely to forest-dependent taxa, should be taken into account when setting policy and sustainability guidelines for oil palm plantations, both in areas undergoing conversion from forest and in existing oil palm plantations where forest restoration is required.

ecology↗