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Biology subjects

Jamshidi, S.

Publications and source records attributed to Jamshidi, S..

4 recordsLinked to original sources

Controllable Point-Light Displays Implemented in a game engine for biological motion research

Biological motion perception plays a critical role in survival and social communication across species. Point-light displays (PLDs), which represent body movement using only a small set of joint markers, have long served as an effective tool for isolating motion cues from other visual features. However, existing methods for generating PLDs, ranging from filmed actors with reflective markers to markerless motion extraction and motion-capture datasets, present limitations in cost, accessibility, flexibility, or ecological validity. In particular, many laboratories lack the resources to create customizable stimuli that allow systematic manipulation of movement parameters. In this article, we introduce a practical and easily modifiable method for producing fully controllable 3D PLDs using freely available animation rigs and the Unity game engine. Our approach enables real-time control of depth cues and directional motion without the need for motion capture equipment or specialized filming environments. To demonstrate the utility of the method, we conducted a psychophysical experiment comparing the perception of biological and non-biological motion. The results replicate the well-documented forward-motion perceptual bias for biological stimuli and highlight differences in how observers interpret motion direction across stimulus classes. This method offers a convenient, accessible, and adaptable tool for research on motion perception and social cognition.

neuroscience↗

ImmCellTyper: an integrated computational pipeline for systematic mining of Mass Cytometry data to assist deep immune profiling

Mass cytometry, also known as Cytometry by time-of-flight (CyTOF), is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level. This technology significantly advances clinical research in immune monitoring and the interrogation of immune cell populations. Nevertheless, the vast amount of data generated by CyTOF poses a daunting challenge for analysis. To address this, we describe ImmCellTyper (https://github.com/JingAnyaSun/ImmCellTyper), a novel and robust toolkit designed for CyTOF data analysis. The analytical framework incorporates an in-house developed semi-supervised clustering tool named BinaryClust, which first characterises main cell lineages, followed by in-depth interrogation for population of interest using unsupervised methods. BinaryClust was benchmarked with existing clustering tools and demonstrated superior accuracy and speed across two datasets comprising around 4 million cells, performing as good as manual gating by human experts. Furthermore, this computational pipeline provides a variety of visualization and analytical tools spanning from quality control to differential analysis, which can be tailored to users specific needs, aiming to provide a one-stop solution for CyTOF data analysis. The general workflow consists of five key steps: 1) Batch effect evaluation and correction, 2) Data quality control and pre-processing, 3) Main cell lineage characterisation and quantification, 4) Extraction and in-depth investigation of cell type of interest; 5) Differential analysis of cell abundance and functional marker expression (supporting multiple study groups). Overall, ImmCellTyper integrates experts biological knowledge in a semi-supervised fashion to accurately deconvolute well-defined main cell lineages, while also preserving the potential of unsupervised approaches to discover novel cell subsets and providing a user-friendly toolset to remove the analytical barrier for high-dimensional immune profiling.

bioinformatics↗

Evaluation of affinity-purification coupled to mass spectrometry approaches for capture of short linear motif-based interactions

Low affinity and transient protein-protein interactions, such as short linear motif (SLiM)-based interactions, require dedicated experimental tools for discovery and validation. Here, we evaluated and compared biotinylated peptide pulldown and protein interaction screen on peptide matrix (PRISMA) coupled to mass-spectrometry (MS) using a set of peptides containing interaction motifs. Eight different peptide sequences that engage in interactions with three distinct protein domains (KEAP1 Kelch, MDM2 SWIB, and TSG101 UEV) with a wide range of affinities were tested. We found that peptide pulldown can be an effective approach for SLiM validation, however, parameters such as protein abundance and competitive interactions can prevent the capture of known interactors. The use of tandem peptide repeats improved the capture and preservation of some interactions. When testing PRISMA, it failed to provide comparable results for a model peptide that successfully pulled down a known interactor using biotinylated peptide pulldown. Overall, in our hands, we find that albeit more laborious, biotin-peptide pulldown was more successful in terms of validation of known interactions. Our results highlight that the tested affinity-capture MS-based methods for validation of SLiM-based interactions from cell lysates are suboptimal, and we identified parameters for consideration for method development.

biochemistry↗

Integron Gene Cassettes Harboring Novel Variants of D-Alanine-D-Alanine Ligase Confer High-level Resistance to D-Cycloserine

During a PCR-based screen of antibiotic resistance genes (ARGs) associated with integrons in saliva-derived metagenomic DNA of healthy human volunteers, two novel variants of genes encoding a D-alanine-D-alanine ligase (ddl6 and ddl7) located within gene cassettes in the first position of a reverse integron were identified. Treponema denticola was identified as the likely host of the ddl cassettes. Both ddl6 and ddl7 conferred high level resistance to D-cycloserine when expressed in Escherichia coli with ddl7 conferring four-fold higher resistance to D-cycloserine compared to ddl6. A SNP was found to be responsible for this difference in resistance phenotype between both ddl variants. Molecular dynamics simulations were used to explain the mechanism of this phenotypic change at the atomic scale. A hypothesis for the evolutionary selection of ddl containing integron gene cassettes is proposed, based on molecular docking of plant metabolites within the ATP and D-cycloserine binding pockets of Ddl. Significance StatementThe drivers of antimicrobial resistance are varied and numerous. One such hypothesis is that compounds not normally considered to be antibiotics may be able to select for genes that can provide resistance to conventional antibiotics. Here we provide evidence that dietary flavonoids are likely to provide the selective pressure for two novel variants of the ddl gene, encoding D-alanine-D-alanine ligases, to be maintained as the first gene cassette of a reverse integron detectable in the human oral cavities from both the UK and Bangladesh. We show that Ddl is functional, able to confer resistance to D-cycloserine and that the dietary flavonoids quercetin and apigenin are likely able to compete with both ATP and D-cycloserine within their Ddl binding sites.

microbiology↗