Biology subjects

Archibald, J.

Publications and source records attributed to Archibald, J..

4 recordsLinked to original sources

bioRxiv2025

Benchmarking the Impact of Anatomical Segmentation on In Vivo Magnetic Resonance Spectroscopy

PurposeEstimation of metabolite concentrations in brain magnetic resonance spectroscopy (MRS) requires correction for differences in tissue water content, relaxation properties, and the proportions of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Accurate knowledge of the relative proportions of these tissue classes within the volume of interest is therefore essential for reliable quantification. Commonly used brain segmentation tools differ in their algorithms, priors, and implementation, potentially introducing variability in MRS-derived concentration estimates. This study investigates the impact of segmentation software on estimated absolute concentrations. MethodsThree segmentation software tools, ANTs, FSL, and SPM, were evaluated. Segmentations were applied to an in vivo test-retest MR dataset to assess (1) differences in estimated tissue fractions, and (2) how these differences propagate into tissue-corrected metabolite concentrations. As an additional validity check and biological benchmark of segmentation performance, age-related associations with GM and total creatine (tCr) were examined. ResultsSignificant differences (p < 0.0001) were observed in tissue fraction estimates between segmentation tools, leading to differences in metabolite concentration estimates of up to 9% under identical acquisition and modeling conditions. Although the strength of the correlation varied between segmentation methods, no statistically significant differences were found. ConclusionThe choice of segmentation methodology contributed substantially to variability in MRS "absolute" metabolite concentration estimates. These results underscore the need for transparent segmentation reporting to ensure reproducibility and cross-study comparability in MRS research. Quantifying the segmentation-driven variability allows researchers to contextualize cross-study differences, helping determine whether observed effects are methodological or biologically meaningful.

neuroscience↗

bioRxiv2025

Test-retest reliability of multi-metabolite edited MRS at 3T using PRESS and sLASER

PurposeSpectral editing is the most common MRS approach for noninvasive in vivo measurement of low-concentration, strongly overlapped metabolites in the brain, such as {gamma}-aminobutyric acid (GABA) and glutathione (GSH). Multi-metabolite editing methods, including HERMES and HERCULES, have recently been introduced, where multiple J-coupled metabolites can be edited in a single acquisition without increasing total scan time. Yet little is known regarding the reliability of these methods. This study assessed the test-retest reliability of HERMES and HERCULES, where volume localization was achieved using either PRESS or sLASER. MethodsSixteen healthy adult volunteers were scanned twice in two separate sessions. Single-voxel edited MRS data were acquired in the medial parietal lobe using the following sequences: (1) HERMES-PRESS; (2) HERMES-sLASER; (3) HERCULES-PRESS; (4) HERCULES-sLASER. Spectra were processed and metabolites were quantified using the Osprey software. Data quality metrics and reliability statistics were estimated for all four acquisitions. ResultsHERMES-sLASER demonstrated lower within-subjects coefficients of variation (CVws) for GSH, glutamine (Gln), and glutamate (Glu) + Gln (Glx), suggesting improved reliability compared to HERMES-PRESS. However, GABA + co-edited macromolecules (GABA+) and Glu showed higher CVws for HERMES-sLASER. HERCULES-sLASER produced better reliability than HERCULES-PRESS for GABA+, GSH, Glu, Gln, Glx, aspartate (Asp), and lactate (Lac). N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) showed higher CVws for HERCULES-sLASER. These findings suggest that sLASER may be more advantageous than PRESS for volume localization in simultaneous multi-metabolite editing. ConclusionUsing sLASER yielded better test-retest reliability for most metabolites than using PRESS for volume localization for HERMES and HERCULES.

neuroscience↗

bioRxiv2025

Does the Brain's E:I Balance Really Shape Long-Range Temporal Correlations? Lessons Learned from 3T MRI

A 3T multimodal MRI study of healthy adults (n=19; 10 female; 21.3 - 53.4 years) was performed to investigate the relationship between fMRI long-range temporal correlations and excitatory/inhibitory balance. The study objective was to determine if the Hurst exponent (H) -- an estimate of the self-correlation and signal complexity -- of the blood-oxygen-level-dependent signal is correlated with the excitatory-inhibitory (E:I) ratio. E:I has been proposed to serve as a control parameter for brain criticality -- the theory that the brain operates near a critical point between order and disorder, optimizing information processing and adaptability -- which H is believed to be a measure of. Thus, understanding if H and E:I are correlated would clarify this relationship. Moreover, findings in this domain have implications for neurological and neuropsychiatric conditions with disrupted E:I balance, such as autism spectrum disorder, schizophrenia, and Alzheimers disease. From a practical perspective, H is easier to accurately measure than E:I ratio at 3T MRI. If H can serve as a proxy for E:I, it may serve as a more practical clinical biomarker for this imbalance and for neuroscience research in general. The study collected functional MRI and magnetic resonance spectroscopy data during rest and movie-watching. H was found to increase with movie-watching compared to rest, while E:I (glutamate/GABA) did not change between conditions. H and E:I were not correlated during either movie-watching or rest. This study represents the first attempt to investigate this connection in vivo in humans. We conclude that, at 3T and with our particular methodologies, no association was found. We end with lessons learned and suggestions for future research.

neuroscience↗

bioRxiv2023

Influenza A virus NS1 effector domain is required for PA-X mediated host shutoff

Many viruses inhibit general host gene expression to limit innate immune responses and gain preferential access to the cellular translational apparatus for their own protein synthesis. This process is known as host shutoff. Influenza A viruses (IAVs) encode two host shutoff proteins: nonstructural protein 1 (NS1) and polymerase acidic X (PA-X). NS1 inhibits host nuclear pre-messenger RNA maturation and export, and PA-X is an endoribonuclease that preferentially cleaves host spliced nuclear and cytoplasmic messenger RNAs. Emerging evidence suggests that in circulating human IAVs NS1 and PA-X co-evolve to ensure optimal magnitude of general host shutoff without compromising viral replication that relies on host cell metabolism. However, the functional interplay between PA-X and NS1 remains unexplored. In this study, we sought to determine if NS1 function has a direct effect on PA-X activity by analyzing host shutoff in A549 cells infected with wild type or mutant IAVs with NS1 effector domain deletion. This was done using conventional quantitative reverse transcription polymerase chain reaction techniques and direct RNA sequencing using nanopore technology. Our previous research on the molecular mechanisms of PA-X function identified two prominent features of IAV infected cells: nuclear accumulation of cytoplasmic poly(A) binding protein (PABPC1) and increase in nuclear poly(A) RNA abundance relative to the cytoplasm. Here we demonstrate that NS1 effector domain function augments PA-X host shutoff and is necessary for nuclear PABPC1 accumulation. By contrast, nuclear poly(A) RNA accumulation is not dependent on either NS1 or PA-X mediated host shutoff and is accompanied by nuclear retention of viral transcripts. Our study demonstrates for the first time that NS1 and PA-X effects on host gene expression are not simply additive and that these factors functionally interact in mediating host shutoff. IMPORTANCERespiratory viruses including influenza A virus continue to cause annual epidemics with high morbidity and mortality due to limited effectiveness of vaccines and antiviral drugs. Among the strategies evolved by viruses to evade immune responses is host shutoff - a general blockade of host messenger RNA and protein synthesis. Disabling influenza A virus host shutoff is being explored in live attenuated vaccine development as an attractive strategy for increasing their effectiveness by boosting antiviral responses. Influenza A virus encodes two proteins that function in host shutoff: the non-structural protein 1 (NS1) and the polymerase acidic X (PA-X). We and others have characterised some of the NS1 and PA-X mechanisms of action and the additive effects that these viral proteins may have in ensuring the blockade of host gene expression. In this work we examined whether NS1 and PA-X functionally interact and discovered that NS1 is required for PA-X to function effectively. This work significantly advances our understanding of influenza A virus host shutoff and identifies new potential targets for therapeutic interventions against influenza and further informs development of improved live attenuated vaccines.

microbiology↗