Biology subjects

Cameron, G.

Publications and source records attributed to Cameron, G..

4 recordsLinked to original sources

bioRxiv2025

Machine learning identifies routine blood tests as accurate predictive measures of pollution-dependent poor cognitive function

BackgroundSeveral modifiable risk factors for dementia and related neurodegenerative diseases have been identified including education level, socio-economic status, and environmental exposures - however, how these population-level risks relate to individual risk remains elusive. To address this, we assess over 450 potential risk factors in one deeply clinically and demographically phenotyped cohort using random forest classifiers to determine predictive markers of poor cognitive function. This study aims to understand early risk factors for dementia by identifying predictors of poor cognitive performance amongst a comprehensive battery of imaging, blood, atmospheric pollutant and socio-economic measures. MethodsRandom forest modelling was used to determine significant predictors of poor cognitive performance in a cohort of 324 individuals (age 61.6 {+/-} 4.8 years; 150 males, 174 females) without extant neurological disease. 457 features were assessed including brain imaging measures of volume and iron deposition, blood measures of anaemia, inflammation, and heavy metal levels, social deprivation indicators and atmospheric pollution exposure. ResultsRoutinely assessed markers of anaemia including mean corpuscular haemoglobin concentration were identified as robust predictors of poor general cognition, where both extremes (low and high) were associated with poor cognitive performance. The strongest, most consistent predictors of poor cognitive performance were environmental measures of atmospheric pollution, in particular, lead, carbon monoxide, and particulate matter. Feature analysis demonstrated a significant negative relationship between low mean corpuscular haemoglobin concentration and high levels of atmospheric pollutants highlighting the potential of routinely assessed blood tests as a predictive measure of pollution-dependent cognitive functioning, at an individual level. ConclusionsTaken together, these data demonstrate how routine, inexpensive medical testing and local authority initiatives could help to identify and protect at-risk individuals. These findings highlight the potential to identify individuals for targeted, cost effective medical and social interventions to improve population cognitive health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/632396v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1cda09org.highwire.dtl.DTLVardef@2e9243org.highwire.dtl.DTLVardef@1849bfcorg.highwire.dtl.DTLVardef@11cf9aa_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Copper resistance in Legionella pneumophila: role of genetic factors and host cells.

Copper is frequently found in drinking water due to its presence in the natural environment and the widespread usage of copper pipes. This toxic metal has a well-known antimicrobial activity, an activity harnessed in copper-silver ionization (CSI) to eliminate the opportunistic pathogen Legionella pneumophila from engineered water systems. Despite utilizing the antimicrobial properties of copper in Legionella control, little is known about how copper containing environments affect L. pneumophila populations. The goal of this study is to understand how L. pneumophila responds to copper within a hot water distribution system (HWDS) environment. To answer this question, different sequence types and regulatory mutants were exposed to copper to compare their survival. L. pneumophila isolates of 4 sequence types from 3 different HWDSs exhibited a wide diversity of phenotypes after copper stress. The {Delta}letA and {Delta}letS mutants were sensitive to copper, indicating that the LetAS two component system is important for copper resistance. Additionaly, transmissive phase cultures were more resistant to copper than replicative phase cultures. Therefore, the regulation of entry into transmissive phase by the LetAS system is essential for L. pneumophilas ability to survive copper stress. In a water system, L. pneumophila replicates within eukaryotic hosts. When cocultured with the host ciliate Tetrahymena pyriformis, L. pneumophila was more resistant to copper than when the bacteria were in a monoculture. No difference in L. pneumophila replication inside of hosts in cocultures with or without copper was observed. This result confirms that the presence of host cells protects L. pneumophila from copper stress. Therefore, presence of host cells in water system may limit the efficacy of copper-based control strategies.

microbiology↗

bioRxiv2022

Sister chromatid cohesion establishment during DNA replication termination

The cohesin complex tethers sister chromatids together from the moment they are generated in S-phase until their separation in anaphase1,2. This fundamental phenomenon, called sister chromatid cohesion, underpins orderly chromosome segregation. The replisome complex coordinates cohesion establishment with replication of parental DNA3. Cohesion can be established by cohesin complexes bound to DNA before replication4,5, but how replisome interaction with pre-loaded cohesin complexes results in cohesion is not known. Prevailing models suggest cohesion is established by replisome passage through the cohesin ring or by transfer of cohesin behind the replication fork by replisome components5. Unexpectedly, by visualising single replication forks colliding with pre-loaded cohesin complexes, we find that cohesin is pushed by the replisome to where a converging replisome is met. Whilst the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA. We demonstrate that these cohesin molecules tether the newly replicated sister DNAs together. Our results support a new model where sister chromatid cohesion is established during DNA replication termination, providing important insight into the molecular mechanism of cohesion establishment.

biophysics↗

bioRxiv2019

Mechanism of RPA-Facilitated Processive DNA Unwinding by the Eukaryotic CMG Helicase

The DNA double helix is unwound by the Cdc45/Mcm2-7/GINS (CMG) complex at the eukaryotic replication fork. While isolated CMG unwinds duplex DNA very slowly, its fork unwinding rate is stimulated by an order of magnitude by single-stranded DNA binding protein, RPA. However, the molecular mechanism by which RPA enhances CMG helicase activity remained elusive. Here, we demonstrate that engagement of CMG with parental double-stranded DNA (dsDNA) at the replication fork impairs its helicase activity, explaining the slow DNA unwinding by isolated CMG. Using single-molecule and ensemble biochemistry, we show that binding of RPA to the excluded DNA strand prevents duplex engagement by the helicase and speeds up CMG-mediated DNA unwinding. When stalled due to dsDNA interaction, DNA rezipping-induced helicase backtracking re-establishes productive helicase-fork engagement underscoring the significance of plasticity in helicase action. Together, our results elucidate the dynamics of CMG at the replication fork and reveal how other replisome components can mediate proper DNA engagement by the replicative helicase to achieve efficient fork progression.

biochemistry↗