Biology subjects

Shah, N. J.

Publications and source records attributed to Shah, N. J..

7 recordsLinked to original sources

bioRxiv2025

Evaluation of visual performance for RCS rats: A tailor-made OMR setup via DeepLabCut and PsychoPy with a customized algorithm

In this study, we developed an optimized optomotor response (OMR) setup for rats based on existing commercial systems and introduced a novel method that integrates DeepLabCut, PsychoPy, and custom algorithms to automate OMR performance evaluation in rats. Our primary findings revealed the optimal spatial frequency (SF) and grating velocity for pigmented Royal College of Surgeons (RCS) and wild-type (WT) rats. The RCS rats, a model for retinal degeneration, displayed normal OMR performance at postnatal days 30 (P30) and 50 (P50), but a significant decline was observed at 3 months. In most rats aged 6 and 12 months, the percentage of correct responses (PoC) was 50%, indicating blindness. The high efficiency and reproducibility of our non-invasive OMR test, along with its suitability for post-surgical and retinal degeneration models, underscores its potential for broad applications in visual performance evaluation.

neuroscience↗

bioRxiv2025

Ultra-High Resolution TR-external EPIK with Deep Learning Image Reconstruction for Enhanced Characterisation of Cortical Depth-dependent Neural Activity

The detection of neural signals using functional MRI at the laminar or columnar level enables non-invasive exploration of fundamental brain function processing and the interconnected pathways within intracortical tissues. The growing interest in this research area is driven by advancements in fMRI acquisition techniques that enhance spatial resolution for high-fidelity mapping. However, the submillimetre voxel sizes commonly employed in layer-specific fMRI studies raise concerns about relatively low signal-to-noise ratios and increased image artefacts in reconstructed images, ultimately limiting the precise delineation of cortical depth-dependent functional activities. This work aims to address this issue by incorporating a deep learning technique for enhanced image reconstruction of the submillimetre fMRI data, acquired with echo-planar-imaging with keyhole (EPIK) combined with the repetition-time-external (TR-external) EPI phase correction scheme. Our network was trained in a self-supervised, scan-specific manner using the sampling strategy from zero-shot self-supervised learning (ZS-SSL) method, which has gained attention for high-resolution MR image reconstruction. Healthy volunteers participated in this study, and the performance of the developed method was evaluated in direct comparison to the conventional reconstruction method using datasets acquired at 7T. The deep learning reconstruction produced reconstructed images with significantly higher SNR than the conventional method, which was further quantitatively validated through histogram analysis. This enhancement was consistent across all slice locations, demonstrating the reliability of the scan-specific deep learning technique.

neuroscience↗

bioRxiv2023

Understanding early reproductive failure in turtles and tortoises

Turtles and tortoises (Order Testudines) are facing an extinction crisis, and ecosystems are at risk of collapsing with the loss of key roles they play. Hatching failure is a crucial barrier to population growth and persistence, but its causes are poorly understood, and it is unknown whether fertilisation rates are declining as many populations become smaller and more female-biased. Here, we first show that fertilisation rates are considered in only a very small proportion of studies of turtle and tortoise hatching success, and those studies that do attempt to measure fertilisation rates use unreliable methods. We also show that studies of hatching success are biased towards marine turtles, as opposed to freshwater and terrestrial species, and wild rather than captive populations. We address the lack of reliable methods for assessing fertilisation rates in turtles and tortoises by developing and testing a microscopy-based method for detecting perivitelline membrane (PVM) bound sperm and embryonic nuclei in the germinal disc of unhatched eggs. We demonstrate that this method can provide unequivocal evidence of egg fertilisation in three different turtle and tortoise species from both captive and wild populations, even after eggs have been left in the nest for the full incubation period. This approach therefore represents a valuable new tool for monitoring egg fertility and embryo survival rates in turtles and tortoises, with the potential to provide important insights into the underlying drivers of reproductive failure in threatened populations.

zoology↗

bioRxiv2021

Engineered chimeras unveil swappable modular features of fatty acid and polyketide synthase acyl carrier proteins

The strategic redesign of microbial biosynthetic pathways is a compelling route to access molecules of diverse structure and function in a potentially environmentally sustainable fashion. The promise of this approach hinges on an improved understanding of acyl carrier proteins (ACPs), which serve as central hubs in biosynthetic pathways. These small, flexible proteins mediate the transport of molecular building blocks and intermediates to enzymatic partners that extend and tailor the growing natural products. Past combinatorial biosynthesis efforts have failed due to incompatible ACP-enzyme pairings. Herein we report the design of chimeric ACPs with features of the actinorhodin polyketide synthase ACP (ACT) and of the E. coli fatty acid synthase (FAS) ACP (AcpP). We evaluate the ability of the chimeric ACPs to interact with the E. coli FAS ketosynthase FabF, which represents an interaction essential to building the carbon backbone of the synthase molecular output. Given that AcpP interacts with FabF but ACT does not, we sought to exchange modular features of ACT with AcpP to confer functionality with FabF. The interactions of chimeric ACPs with FabF were interrogated using sedimentation velocity experiments, surface plasmon resonance analyses, mechanism-based crosslinking assays, and molecular dynamics simulations. Results suggest that the residues guiding AcpP-FabF compatibility and ACT-FabF incompatibility may reside in the loop I, -helix II region. These findings can inform the development of strategic secondary element swaps that expand the enzyme compatibility of ACPs across systems and therefore represent a critical step towards the strategic engineering of unnatural natural products.

biochemistry↗

bioRxiv2021

Mapping of Whole-Brain Resting-State Networks with Half-Millimetre Resolution

Resting-state fMRI has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 x 0.7 x 0.7 mm3, with only partial brain coverage. This work presents a novel fMRI method, TR-external EPI with keyhole (TR-external EPIK), which can provide a nominal spatial resolution of 0.51 x 0.51 x 1.00 mm3 (0.26 mm3 voxel) with whole-brain coverage. TR-external EPIK enabled the identification of various resting-state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high-resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.

neuroscience↗

bioRxiv2020

Excitatory-Inhibitory Balance within EEG Microstates and Resting-state fMRI Networks: Assessed via Simultaneous PET-MR-EEG Imaging

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and GABA ({gamma} -aminobutyric acid) and the receptor availability (RA) of GABAA and mGluR5, remains unexplored. This study investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAA and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPND of GABAA relative to mGluR5 BPND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest.

neuroscience↗

bioRxiv2018

MR-PET head motion correction based on co-registration of multi-contrast MR images

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous Magnetic Resonance-Positron Emission Tomography (MR-PET) makes it possible to estimate head motion information from high-resolution MR images and then correct motion artefacts in PET images. In this paper, we introduce a fully automated PET motion correction method, MR-guided MAF, based on the co-registration of multi-contrast MR images. The performance of the MR-guided MAF method was evaluated using MR-PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18-F]FDG). Compared with conventional methods, MR guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR-PET scanners. The fully automated motion estimation method has been implemented as a publicly available web-service.

bioinformatics↗