Biology subjects

Ang, J.

Publications and source records attributed to Ang, J..

8 recordsLinked to original sources

bioRxiv2025

Hepatic isomiR landscaping reveals new biological insights into metabolic dysfunction in steatotic liver disease

Post-transcriptionally modified microRNA (miRNA), called isomiRs, expand the repertoire of transcripts that can leveraged for therapeutic targets and biological insights. However, the expression of isomiRs has not been characterized in metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we assessed the isomiR expression profile in liver biopsies from 79 patients with MASLD and modeled their potential role in disease biology. MiRNAs represented 75% of the sequencing reads and over 65% of them were attributed to isomiRs, demonstrating their higher expression and diversity compared to canonically annotated miRNAs. Differential expression and machine-learning analyses were used to identify 173 isomiRs associated to MASLD severity and 58 isomiRs associated to fibrosis score. Candidate target mRNAs were identified for each isomiR based on sequence complementarity. Using matched mRNA sequencing data, and supported by data from an independent study, we proposed key dysregulated mRNA targets involved in a selection of 33 disease-associated pathways. Importantly, isomiRs offered novel and unique mRNA targets compared to the canonical miRNA, e.g. isomiR-122 targeting INSIG1 (insulin and cholesterol metabolism), and isomiR-21 targeting HMGCS2 and PPARA (PARR and TGF-beta signaling). Our work advances knowledge regarding the role of isomiRs in MASLD and lays a foundation for therapeutic targets identification. HighlightsOur results provide a comprehensive analysis of microRNA (isomiRs) in liver tissue. Machine learning identified isomiRs whose expression is associated with MASLD. Multi-omic analysis uncovered novel isomiR regulatory mechanisms involved in MASLD.

bioinformatics↗

bioRxiv2025

Hemodynamic traveling waves transport musical codes faster than language codes via shared bilateral streams

What takes precedence in our brain: music or language? Here we used rapid phase-encoded fMRI to explore spatiotemporal brain dynamics during naturalistic music and language tasks, seeking to track down the entire perception-to-production process and compare the speed of information transfer between the two domains. We found largely shared streams of traveling waves bilaterally, along which musical codes were transported faster than language codes for identical visual input.

neuroscience↗

bioRxiv2024

Respiratory mucosal administration of DNA aptamer nanomaterials protects against antigenically diverse SARS-CoV-2 variants

The ongoing COVID-19 pandemic has highlighted the need for innovative therapeutic strategies to combat rapidly evolving pathogens that challenge the efficacy of traditional vaccines and monoclonal antibody treatments. Here, we explored the potential of TMSA52, a previously described homotrimeric DNA aptamer as a universal prophylactic and therapeutic agent against SARS-CoV-2. TMSA52 demonstrates exceptional binding affinities and broad neutralization against diverse SARS-CoV-2 variant spike proteins that are further enhanced through multimerization onto lamellar iridium nanoplates. Respiratory mucosal delivery of TMSA52 nanomaterials was well-tolerated. Surprisingly, TMSA52 offered potent protection from infection with ancestral SARS-CoV-2 on-par with monoclonal antibodies, and superior protection against antigenically distant SARS-CoV-2 variants. These findings establish DNA aptamers as a promising, cost-effective, and scalable alternative to traditional monoclonal antibody therapies. This study underscores the potential of aptamer-based platforms as a next-generation strategy to enhance global pandemic preparedness and expand our arsenal of infectious disease countermeasures.

immunology↗

bioRxiv2023

Extracellular modulation of TREK-2 activity with nanobodies provides insights into the mechanism of K2P channel regulation

Potassium channels of the Two-Pore Domain (K2P) subfamily, KCNK1-KCNK18, play crucial roles in controlling the electrical activity of many different cell types and represent attractive therapeutic targets. However, the identification of highly selective small molecule drugs against these channels has been challenging due to the high degree of structural and functional conservation that exists not only between K2P channels, but across the whole K+ channel superfamily. To address the issue of selectivity, we generated camelid antibody fragments (nanobodies) against the TREK-2 (KCNK10) K2P K+ channel and identified selective binders including several that directly modulate channel activity. X-ray crystallography and CryoEM data of these nanobodies in complex with TREK-2 also reveal insights into their mechanisms of activation and inhibition via binding to the extracellular loops and Cap domain, as well as their suitability for immunodetection. It also facilitated design of a biparatropic inhibitory nanobody with markedly improved affinity and efficacy. These new tools therefore provide important insights into TREK channel gating and suggest alternative, highly selective approach to modulation of K2P channel activity via their extracellular domains.

biophysics↗

bioRxiv2021

Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individuals titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

immunology↗

bioRxiv2021

Towards CRISPR/Cas9-based gene drive in the diamondback moth Plutella xylostella

Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipterans, yeast and mice, for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and sgRNA expression in the diamondback moth, (Plutella xylostella), and test the first split-drive system in a lepidopteran. The diamondback moth is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable, Cas9-medated germline cleavage, as well as maternal and paternal Cas9 deposition was observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drive-based genetic control strategies in DBM or other lepidopterans.

genetics↗

bioRxiv2021

MetaPro: A scalable and reproducible data processing and analysis pipeline for metatranscriptomic investigation of microbial communities

BackgroundWhole microbiome RNASeq (metatranscriptomics) has emerged as a powerful technology to functionally interrogate microbial communities. A key challenge is how best to process, analyze and interpret these complex datasets. In a typical application, a single metatranscriptomic dataset may comprise from tens to hundreds of millions of sequence reads. These reads must first be processed and filtered for low quality and potential contaminants, before being annotated with taxonomic and functional labels and subsequently collated to generate global bacterial gene expression profiles. ResultsHere we present MetaPro, a flexible, massively scalable metatranscriptomic data analysis pipeline that is cross-platform compatible through its implementation within a Docker framework. MetaPro starts with raw sequence read input (single end or paired end reads) and processes them through a tiered series of filtering, assembly and annotation steps. In addition to yielding a final list of bacterial genes and their relative expression, MetaPro delivers a taxonomic breakdown based on the consensus of complementary prediction algorithms, together with a focused breakdown of enzymes, readily visualized through the Cytoscape network visualization tool. We benchmark the performance of MetaPro against two current state of the art pipelines and demonstrate improved performance and functionality. ConclusionMetaPro represents an effective integrated solution for the processing and analysis of metatranscriptomic datasets. Its modular architecture allows new algorithms to be deployed as they are developed, ensuring its longevity. To aid user uptake of the pipeline, MetaPro, together with an established tutorial that has been developed for educational purposes is made freely available at https://github.com/ParkinsonLab/MetaPro. The software is freely available under the GNU general public license v3.

bioinformatics↗

bioRxiv2020

Metabolic Buffer Analysis Reveals the Simultaneous, Independent Control of ATP and Adenylate Energy Ratios

Determining the underlying principles behind biological regulation is important for understanding the principles of life, treating complex diseases, and creating de novo synthetic biology. Buffering - the use of reservoirs of molecules to maintain molecular concentrations - is a widespread and important mechanism for biological regulation. However, a lack of theory has limited our understanding of its roles and quantified effects. Here, we study buffering in energy metabolism using control theory and novel buffer analysis. We find that buffering can enable the simultaneous, independent control of multiple coupled outputs. In metabolism, adenylate kinase and AMP deaminase enable simultaneous control of ATP and adenylate energy ratios, while feedback on metabolic pathways is fundamentally limited to controlling one of these outputs. We also quantify the regulatory effects of the phosphagen system - the above buffers and creatine kinase - revealing which mechanisms regulate which outputs. The results are supported by human muscle and mouse adipocyte data. Together, these results illustrate the synergy of feedback and buffering in molecular biology to simultaneously control multiple outputs.

systems biology↗