Biology subjects

Cheng, S. H.

Publications and source records attributed to Cheng, S. H..

5 recordsLinked to original sources

bioRxiv2025

Flexibility and modulation of translation initiation in enterovirus genomes

Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA-13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA-13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. These findings demonstrate the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems.

microbiology↗

bioRxiv2023

Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages

The susceptibility of cancer cells to DNA damages is influenced by their microenvironment. For example, unirradiated neighbors of irradiated cells can produce signals that reduce DNA damages. This phenomenon, known as Radiation-Induced Rescue Effect (RIRE), has profound implications on the efficacy of radiotherapy. Using bystander cells cocultured with mock-irradiated cells as a control, we demonstrated, for the first time, two types of RIRE. Conditioned medium from naive bystander cells, i.e., cells not exposed to irradiated cells, could mitigate UV-induced DNA damages in human breast carcinoma MCF7 cells, as judged by phospho-H2AX and 53BP1 immunostaining. This protective effect could be further enhanced by the prior treatment of bystander cells with factors from UV-irradiated cells. We named the former effect "basal RIRE" and the latter "active RIRE" which were cell type-dependent. As bystanders, MCF7 showed a significant active RIRE, whereas THP1-derived macrophages showed a strong basal RIRE but no active RIRE. Interestingly, RIRE of macrophages could further be modulated by polarisation. The basal RIRE of macrophages was abolished by M1 polarisation, while M2 and Tumour Associated Macrophages (TAM) demonstrated pronounced basal and active RIRE. When mixtures of MCF7 cells and polarised macrophages were used as bystanders, the overall RIRE was dictated by macrophage phenotypes: RIRE was suppressed by M1 macrophages but significantly enhanced by M2 and TAM. This study shows a previously unappreciated role of the innate immune system in RIRE. Depending on polarised phenotypes, macrophages in the tumour microenvironment can interfere with the effectiveness of radiotherapy by adjusting the RIRE magnitudes.

cancer biology↗

bioRxiv2021

Seascape genomics reveals population structure and local adaptation in a widespread coral reef snail, Coralliophila violacea (Kiener, 1836)

Local adaptation to different environments may reinforce neutral evolutionary divergence, especially in populations in the periphery of a species geographic range. Seascape genomics (high-throughput genomics coupled with ocean climate databases) facilitates the exploration of neutral and adaptive variation in concert, developing a clearer picture of processes driving local adaptation in marine populations. This study used a seascape genomics approach to test the relative roles of neutral and adaptive processes shaping population divergence of a widespread coral reef snail, Coralliophila violacea. We collected C. violacea from colonies of their coral host (Porites spp.) at ten locations spanning a large portion of their geographic range. We used RAD-seq to investigate possible local adaptation via genetic-environmental associations with five ocean climate variables. Four genetic partitions were concordant with regions previously observed in mtDNA (Indian Ocean, Coral Triangle, and Hawaiian Islands), with the addition of Vietnam and varying isolation and admixture levels. We identified outlier loci (FDR = 0.10, N = 72) among individual localities and between regions (FDR = 0.10, N = 34), suggesting that some loci are putatively under divergent selection. Association analyses showed that the two strongest drivers of local adaptation were the annual range and mean of sea surface temperature. Populations that experience lower sea surface temperatures at the periphery of C. violaceas geographic range drive these associations. Our results show that local adaptation to different environments likely reinforces neutral divergence, especially in peripheral populations.

evolutionary biology↗

bioRxiv2020

Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology

We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.

physiology↗

bioRxiv2019

Illuminating the dark depths inside coral

The ability to observe in situ 3D distribution and dynamics of endosymbionts in corals is crucial for gaining a mechanistic understanding of coral bleaching and reef degradation. Here, we report the development of a tissue clearing (TC)-coupled light sheet fluorescence microscopy (LSFM) method for 3D imaging of the coral holobiont at single-cell resolution. The initial applications have demonstrated the ability of this technique to provide high space-resolution quantitative information of endosymbiont abundance and distribution within corals. With specific fluorescent probes or assays, TC-LSFM also revealed spatial distribution and dynamics of physiological conditions (such as cell proliferation, apoptosis, and hypoxia response) in both corals and their endosymbionts. This tool is highly promising for in situ and in-depth data acquisition to illuminate coral symbiosis and health conditions in the changing marine environment, providing fundamental information for coral reef conservation and restoration.

microbiology↗