Biology subjects

Davis, G. M.

Publications and source records attributed to Davis, G. M..

6 recordsLinked to original sources

bioRxiv2025

Metabolic Trajectories During Surgical Stress in Patients Undergoing Cardiac Surgery

Stress hyperglycemia (SH) during acute illness is linked to adverse surgical outcomes, yet the accompanying metabolic perturbations are incompletely characterized. We profiled longitudinal metabolic changes in adults without diabetes undergoing cardiac surgery to identify pathways associated with perioperative SH (defined as point-of-care glucose [≥]140 mg/dL on [≥]3 readings or [≥]180 mg/dL once). Blood was collected at baseline before surgery (T0) and at 2 h (T1), 24-48 h (T2), and 72-96 h (T3) after surgical initiation. High-resolution metabolomics (LC-MS) was integrated with continuous glucose monitoring and inflammatory/cardiac biomarkers. At T0, several pathways were associated with subsequent SH, including bile acid metabolism, the carnitine shuttle, and fatty-acid oxidation, suggesting preoperative metabolic susceptibility. In longitudinal analyses, participants who developed SH showed coordinated postoperative changes with significant enrichment of pathways not evident at baseline, C21-steroid hormone biosynthesis, glycerophospholipid metabolism, and glycosphingolipid (ceramide) metabolism, consistent with lipid remodeling and inflammatory signaling during surgical stress. Individuals with SH also exhibited higher inflammatory biomarker levels (high-sensitivity C-reactive protein and soluble urokinase plasminogen activator receptor). A machine-learning model using early metabolomic features predicted SH with an area under the receiver operating characteristic curve of 0.86. These findings highlight distinct preoperative and perioperative metabolic trajectories associated with SH and implicate established dysglycemia-related pathways, as well as stress-induced pathways in perioperative metabolic dysregulation. Pathway enrichment analyses were exploratory and hypothesis-generating; validation in larger cohorts and assessment of implications for clinical outcomes are warranted.

biochemistry↗

bioRxiv2025

Endospore integrity and viability of Bacillus subtilis on simulated Martian regolith in rotational UVC radiation exposures

Current understanding of Martian regolith has advanced due to various rover explorations. Due to this, there are now several variants of Martian regolith that are chemically known and commercially available. These simulants are vital for panspermia models that suggest a transfer of simple life throughout the solar system via ejecta containing life from Mars when its surface was more favourable to host life. Bacteria that produce endospores are suitable candidates for these models as they have adequate protection from the harsh conditions of space, particularly against solar radiation. To assess this, the simple endospore former, Bacillus subtilis, was assessed for growth on several Martian regolith that represented different locations and epochs of Mars. This consisted of a conventional Martian regolith, a sulphur rich regolith, and a simulant of the Jezero crater which was thought to have once been flooded with water. We found that the sulphur rich regolith inhibited endospore formation, while the other two variants favoured endospore production. Interestingly, we also identified that pulsing of UVC in a simulation of endospores on rotational ejecta show that endospores break down faster with lower rotational frequency despite receiving the same UVC dose. Moreover, and most strikingly is that viable endospores after surviving UVC dosage displayed elevated expression of the DNA damage SOS response gene, RecA. Importantly, this study suggests that astrobiological approaches that utilise endospore viability as a benchmark for survival require reassessment as genomic integrity may be compromised. ImportanceCurrent panspermia models that explore the potential interplanetary transfer of simple microbes, particularly those that focus on Mars, apply a combination of Martian topology and bacterial survival. This study assesses Bacillus subtilis endospore formation on different Martain regolith mediums and simulates their potential exposure on fast and slow rotations while being exposed to UV radiation to simulate space radiation. We outline what regions of Mars would be suitable for the formation of endospores, and moreover, we assess viable endospores post-exposure for the expression of the SOS DNA damage repair gene, RecA. Endospores that are viable after withstanding near lethal doses of UVC show elevated expression of RecA. While our study adds vital information to understanding Martian topography and microbial survival, our finding RecA expression analysis post-exposure adds important information to our understanding of endospores as a whole and should be factored into future astrobiological approaches.

microbiology↗

bioRxiv2022

Mitochondrial complex I controls blood brain barrier permeability

Mitochondrial electron transport chain (ETC) complexes are key mediators of energy metabolism in astrocytes and neurons, with subsequent effects on memory, behaviour and neurodegeneration. Mitochondrial dysfunction and increased blood brain barrier (BBB) permeability are known pathologies in Parkinsons and Alzheimers diseases. However, knowledge of how ETC activities regulate metabolic flux and influence permeability in the BBB is lacking. Using metabolic flux control analysis we show that complex I is a critical control point for oxidative flux and permeability in brain microvascular endothelial cells derived from human induced pluripotent stem cells. Inhibition of complex I activity immediately reduced the transendothelial electrical resistance (TEER) by 60%, leading to an increase in protein transport across the BBB. These events were accompanied by a transient reduction in ATP that was recovered, along with TEER values, over an extended time period. Furthermore, while inhibition of downstream complexes III or IV decreased oxygen respiration rates, no effects on BBB permeability were identified, due to compensatory glycolytic flux and maintenance of ATP synthesis. These data show that mitochondrial complex I is critical for maintaining energy production in endothelial cells and transiently controls BBB permeability, which may contribute to brain disorders where complex I dysfunction is a hallmark.

neuroscience↗

bioRxiv2019

GCNA interacts with Spartan and Topoisomerase II to regulate genome stability.

GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan/DVC-1 and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. We show that GCNA and Topoisomerase 2 (Top2) physically interact and colocalize on condensed chromosomes during mitosis, when Spartan is not present. We show that C. elegans gcna-1 mutants are sensitive to Top2 poison and accumulate mutations consistent with low fidelity repair of DNA damage, leading to loss of fitness and fertility over generations. We also demonstrate that mouse GCNA interacts with TOP2, and Gcna-mutant mice exhibit abnormalities consistent with the inability to process DPCs, including chromatin condensation and crossover defects. Together, our findings provide evidence that GCNA maintains genomic integrity by processing Top2 DPCs in the germline and early embryo, where the genome is challenged with an increased DPC burden.

developmental biology↗

bioRxiv2018

Comprehensive transcriptional profiling of the gastrointestinal tract of ruminants from birth to adulthood reveals strong developmental stage specific gene expression

One of the most significant physiological challenges to neonatal and juvenile ruminants is the development and establishment of the rumen. Using a subset of RNA-Seq data from our high-resolution atlas of gene expression in sheep (Ovis aries) we have provided the first comprehensive characterisation of transcription of the entire the gastrointestinal (GI) tract during the transition from pre-ruminant to ruminant. The dataset comprises 168 tissue samples from sheep at four different time points (birth, one week, 8 weeks and adult). Using network cluster analysis we illustrate how the complexity of the GI tract is reflected in tissue- and developmental stage-specific differences in gene expression. The most significant transcriptional differences between neonatal and adult sheep were observed in the rumen complex. Differences in transcription between neonatal and adult sheep were particularly evident in macrophage specific signatures indicating they might be driving the observed developmental stage-specific differences. Comparative analysis of gene expression in three GI tract tissues from age-matched sheep and goats revealed species-specific differences in genes involved in immunity and metabolism. This study improves our understanding of the transcriptomic mechanisms involved in the transition from pre-ruminant to ruminant. It highlights key genes involved in immunity, microbe recognition, metabolism and cellular differentiation in the GI tract. The results form a basis for future studies linking gene expression with microbial colonisation of the developing GI tract and will contribute towards identifying genes that underlie immunity in early development, which could be utilised to improve ruminant efficiency and productivity.\n\nReference Numbers for Data in the Public RepositoriesThe raw RNA-Sequencing data are deposited in the European Nucleotide Archive (ENA) under study accessions PRJEB19199 (sheep) and PRJEB23196 (goat). Metadata for all samples is deposited in the EBI BioSamples database under group identifiers SAMEG317052 (sheep) and SAMEG330351 (goat).

genomics↗

bioRxiv2018

The TRIM-NHL protein NHL-2 is a Novel Co-Factor of the CSR-1 and HRDE-1 22G-RNA Pathways

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

genetics↗