Biology subjects

Veale, T.

Publications and source records attributed to Veale, T..

2 recordsLinked to original sources

bioRxiv2024

The thermotolerant Arabian killifish, Aphanius dispar, as a novel infection model for human fungal pathogens

Candida albicans: a fungal pathogen, can cause superficial and fatal infections in humans. An important virulence factor in C. albicans dissemination is the transformation from yeast to an invasive hyphal form, which is favoured at human body temperature. Zebrafish, a useful model for studying C. albicans infections, cannot survive at 37{degrees}C. Arabian killifish, Aphanius dispar, an emerging teleost model can tolerate temperatures up to 40 {degrees}C for up to 12 days (independent feeding time) allowing for longer analysis compared to zebrafish. This study introduces A. dispar as a thermo-relevant and a more accurate reporter of the virulence mechanisms relevant to C. albicans as a human pathogen. Using A. dispar, we tested virulence at human skin (30 {degrees}C), body temperature (37 {degrees}C) and a high fever condition (40{degrees}C). Infection by C. albicans at 37{degrees}C and 40{degrees}C significantly increased virulence, reduced survival of AKF embryos and formed invasive hyphal network compared to 30 {degrees}C. Two mutant strains of C. albicans. pmr1{Delta} (with aberrant cell surface glycans) exhibited reduced virulence at 37{degrees}C, whereas rsr1{Delta} (lacking a cell polarity marker) showed less virulence at 30 {degrees}C. Additionally, anti-fungal treatment rescued AKF survival in a dose-dependent manner, indicating AKFs potential for in vivo drug testing. Our data indicates the quantitative and qualitative importance of examining virulence traits at physiologically relevant temperatures and demonstrates an equivalence to findings for systemic infection derived in mouse models. The A. dispar embryo therefore provides an excellent in vivo model system for assessing virulence, drug-testing, and real-time imaging of host-pathogen interactions. Significance StatementThe virulence of many pathogens is dependent on host temperature. We demonstrate that the A. dispar embryo provides an excellent new thermo-relevant alternative to zebrafish and mouse models, which have limitations in terms of the range of temperatures that can be assessed in real-time. In this study, we have assessed C. albicans temperature-based virulence, focusing on human body and human skin temperatures (37, 40 and 30 {degrees}C, respectively) by examining different genetic backgrounds of C. albicans strains. The results indicate different C. albicans strains with genetic background show varied virulence depending on temperature indicating importance of examination of virulence mechanisms at physiological temperatures.

animal behavior and cognition↗

bioRxiv2021

Not all voxels are created equal: reducing estimation bias in regional NODDI metrics using tissue-weighted means

Neurite orientation dispersion and density imaging (NODDI) estimates microstructural properties of brain tissue relating to the organisation and processing capacity of neurites, which are essential elements for neuronal communication. Descriptive statistics of NODDI tissue metrics are commonly analysed in regions-of-interest (ROI) to identify brain-phenotype associations. Here, the conventional method to calculate the ROI mean weights all voxels equally. However, this produces biased estimates in the presence of CSF partial volume. This study introduces the tissue-weighted mean, which calculates the mean NODDI metric across the tissue within an ROI, utilising the tissue fraction estimate from NODDI to reduce estimation bias. We demonstrate the proposed mean in a study of white matter abnormalities in young onset Alzheimers disease (YOAD). Results show the conventional mean induces significant bias that correlates with CSF partial volume, primarily affecting periventricular regions and more so in YOAD subjects than in healthy controls. Due to the differential extent of bias between healthy controls and YOAD subjects, the conventional mean under- or over-estimated the effect size for group differences in many ROIs. This demonstrates the importance of using the correct estimation procedure when inferring group differences in studies where the extent of CSF partial volume differs between groups. These findings are robust across different acquisition and processing conditions. Bias persists in ROIs at higher image resolution, as demonstrated using data obtained from the third phase of the Alzheimers disease neuroimaging initiative (ADNI); and when performing ROI analysis in template space. This suggests that conventional ROI means of NODDI metrics are biased estimates under most contemporary experimental conditions, the correction of which requires the proposed tissue-weighted mean. The tissue-weighted mean produces accurate estimates of ROI means and group differences when ROIs contain voxels with CSF partial volume. In addition to NODDI, the technique can be applied to other multi-compartment models that account for CSF partial volume, such as the free water elimination method. We expect the technique to help generate new insights into normal and abnormal variation in tissue microstructure of regions typically confounded by CSF partial volume, such as those in individuals with larger ventricles due to atrophy associated with neurodegenerative disease.

neuroscience↗