Biology subjects

Tran, H. T.

Publications and source records attributed to Tran, H. T..

10 recordsLinked to original sources

bioRxiv2026

First-Trimester Non-Invasive Prediction of Preterm Birth Using Cell-Free DNA Fragmentomics

ObjectiveTo develop and validate a cell-free DNA (cfDNA) fragmentomic classifier for the early prediction of spontaneous preterm birth (PTB) using routine first-trimester non-invasive prenatal testing (NIPT) data. MethodsA nested case-control study was conducted within a prospective multicenter Vietnamese cohort comprising 286 pregnancies, including 82 spontaneous PTB cases and 204 term controls. Maternal plasma cfDNA collected during routine first-trimester NIPT (median gestational age, 12 weeks) was sequenced to a depth of approximately 20 million reads per sample. Five fragmentomic feature categories including copy number alterations, end-motif composition, nucleosome distance, fragment length, and joint fragment-lengthxend-motif were evaluated for PTB prediction. Machine learning classifiers were developed in a training cohort (n = 228, 65 PTB vs 163TB) and tested in a validation cohort (n = 58, 17 PTB vs 41 TB). ResultsAmong the five fragmentomic feature classes evaluated, 4-mer end-motif (EM) profiles exhibited the most pronounced differences between PTB and term control samples. Consistent with these findings, the EM-based classifier demonstrated the highest discriminative performance in the validation cohort, achieving an AUC of 0.970 (95% CI, 0.912-1.000). At a specificity >90%, the model achieved a sensitivity of 94% (95% CI, 78-100%). ConclusionThese findings demonstrate that cfDNA EM signatures derived from routine first-trimester NIPT can accurately identify pregnancies at risk of spontaneous preterm birth, without additional blood collection or sequencing, thereby extending the clinical utility of existing prenatal screening infrastructure. KEY POINTSO_ST_ABSWhat is already known about this topic?C_ST_ABSO_LICurrent first-trimester prediction strategies based on maternal characteristics, cervical length, and biochemical markers have limited predictive accuracy, particularly in nulliparous women. C_LIO_LIExisting cfDNA-based approaches have shown only modest performance or require additional assays, limiting clinical applicability. C_LI What does this study add?O_LIExisting NIPT sequencing data can be repurposed (without additional blood sampling or sequencing) for accurate prediction of spontaneous preterm birth (AUC=0.970). C_LIO_LIA classifier employing 4-mer end-motif (EM) profiles achieved an AUC of 0.970. At a specificity >90%, the model achieved a sensitivity of 94%. C_LI

genomics↗

bioRxiv2024

Functional classification of tauopathy strains reveals the role of protofilament core residues.

Distinct tau amyloid assemblies underlie diverse tauopathies but defy rapid classification. Cell and animal experiments indicate tau functions as a prion, as different strains propagated in cells cause unique, transmissible neuropathology after inoculation. Strain amplification requires compatibility of the monomer and amyloid template. We used cryo-EM to study one cell-based YFP-tagged strain, resolving its amyloid nature. We then used sequential alanine (Ala) substitution (scan) within tau repeat domain (RD) to measure incorporation to pre-existing tau RD-YFP aggregates. This robustly discriminated strains, defining sequences critical for monomer incorporation. We then created 3R/4R or 4R WT RD (aa 246-408) biosensors. Ala scan of recombinant tau seeds with the Alzheimers Disease fold matched that of AD homogenate. We scanned 22 brain lysates comprising 4 tauopathies. This clustered cases by neuropathological syndrome, revealed the role of amino acids in protofilament folds, and allowed strain discrimination based on amino acid requirements for prion replication. TeaserDiscrimination of tau strains based on the relative contribution of each amino acid to templated propagation of the amyloid.

neuroscience↗

bioRxiv2021

Adenovirus-α-defensin complexes induce NLRP3-associated maturation of human phagocytes via TLR4 engagement

Intramuscular delivery of human adenovirus (HAdV)-based vaccines leads to rapid recruitment of neutrophils, which then release antimicrobial peptides/proteins (AMPs). How these AMPs influence vaccine efficacy over the subsequent 24 hr is poorly understood. In this study, we asked if human neutrophil protein 1 (HNP-1), an -defensin that influences the direct and indirect innate immune responses to a range of pathogens, impacts the innate response of human phagocytes to three HAdV species/types (HAdV-C5, -D26, -B35). We show that HNP-1 binds to the capsids, redirects HAdV-C5, -D26, -B35 to Toll-like receptor 4 (TLR4), which leads to internalization, an NLRP3-mediated inflammasome response, and IL-1{beta} release. Surprisingly, IL-1{beta} release was not associated with notable disruption of plasma membrane integrity. These data further our understanding of HAdV innate immunogenicity and may provide pathways to extend HAdV-based vaccines efficacy.

immunology↗

bioRxiv2021

DIRECT DETECTION OF LISTERIA MONOCYTOGENES BY RECOMBINASE POLYMERASE AMPLIFICATION

Listeria monocytogenes is one of the most common types of food poisoning bacteria which can cause serious foodborne diseases or even lethality. Generally, L. monocytogenes can be detected using traditional microbiology or molecular biology techniques, notably PCR. However, the application of these methods at the field is restricted due to the strict requirement of equipment and skilled personnel. In this study, recombinase polymerase amplification (RPA), an isothermal PCR assay was developed to rapidly detect L. monocytogenes in the crude samples. The results showed that the RPA reaction, without requiring complex thermal cycles, was well-performed in the optimal conditions of 39{degrees}C within only 25 minutes. The limit of detection was identified as 310 fg of L. monocytogenes genomic DNA, which was 1000-fold more sensitive than the conventional PCR. In addition, RPA also succeeded to directly detect L. monocytogenes cells at a concentration as low as 2.5 x 101 Colony Forming Unit (CFU)/ml in pure cultures and 2.5 x 102 CFU/ml in crude samples without sample extraction or processing. Therefore, RPA established in this study could be an alternative standard method to confirm the presence of L. monocytogenes in food. Accordingly, this rapid and sensitive method could be further applied to clinical testing for the diagnosis of L. monocytogenes infection, especially in areas with limited settings.

molecular biology↗

bioRxiv2020

Direct colorimetric LAMP assay for in-field detection of African swine fever virus: a validation study during an outbreak in Vietnam

African Swine Fever (ASF) is a highly infectious viral disease with high mortality. The most recent ASF outbreak in Vietnam occurred in 2019, posing a threat to spread to the neighboring Asian countries. Without a commercial vaccine or efficient chemotherapeutics successfully developed, rapid diagnosis and necessary biosecurity procedures are required to control the disease. While the diagnosis method of ASF recommended by the World Organization of Animal Health is real-time PCR, it is not suitable for in-field detection of the disease. In this study, a colorimetric Loop-Mediated Isothermal Amplification (LAMP) assay was developed and evaluated for ASF virus detection using crude serum samples collected from domestic pigs in Vietnam during the 2019 outbreak. The LAMP results can be readily visualized to naked eyes within 30 minutes without the requirement of DNA extraction and sophisticated equipment. The sensitivity, specificity, and limit of detection of colorimetric LAMP assay were comparable to a commercial diagnostic real-time PCR kit. Results strongly indicate that the developed colorimetric LAMP assay is highly recommended for the in-field diagnosis of ASF.

molecular biology↗

bioRxiv2020

A comparative study of isothermal nucleic acid amplification methods for SARS-CoV-2 detection at point of care

COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread worldwide and put most of the world under lockdown. Despite that there have been emergently approved vaccines for SARS-CoV-2, COVID-19 cases, hospitalizations, and deaths have remained rising. Thus, rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. In this study, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and evaluated. The three methods showed the same limit of detection (LOD) value of 1 copy of the targeted gene per reaction. However, for the direct detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the LOD value of roughly 43.14 genome copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. Moreover, the direct detection of SARS-CoV-2 RNA in simulated patient specimens by iNAATs was also successful. Finally, the ready-to-use lyophilized reagents for LAMP reactions were shown to maintain the sensitivity and LOD value of the liquid assays. The results indicate that the colorimetric lyophilized LAMP kit developed herein is highly suitable for detecting SARS-CoV-2 nucleic acids at point-of-care.

molecular biology↗

bioRxiv2019

ΔN-Tp63 mediates Wnt/β-catenin-induced inhibition of differentiation in basal stem cells of mucociliary epithelia

Mucociliary epithelia provide a first line of defense against pathogens in the airways and the epidermis of vertebrate larvae. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/{beta}-catenin signaling in chronic airway diseases, but underlying mechanisms remain elusive and studies of Wnt signaling in mucociliary cells yield seemingly contradicting results. Employing the Xenopus mucociliary epidermis, the mouse airway, and human airway basal stem cell cultures, we characterize the evolutionarily conserved roles of Wnt/{beta}-catenin signaling in mucociliary cells in vertebrates. Wnt signaling is required in multiciliated cells for cilia formation during differentiation stages, but in Basal cells, Wnt signaling prevents specification and differentiation of epithelial cell types by activating{Delta} N-TP63 expression. We demonstrate that {Delta}N-TP63 is a master transcription factor in Basal cells, which is necessary and sufficient to mediate the Wnt-induced inhibition of differentiation and is required to retain basal stem cells during development. Chronic stimulation of Wnt signaling leads to mucociliary remodeling and Basal cell hyperplasia, but this is reversible in vivo and in vitro, suggesting Wnt inhibition as an option in the treatment of chronic lung diseases. Our work sheds light into the evolutionarily conserved regulation of stem cells and differentiation, resolves Wnt functions in mucociliary epithelia, and provides crucial insights into mucociliary development, regeneration and disease mechanisms.

developmental biology↗

bioRxiv2019

A new transgenic reporter line reveals Wnt-dependent Snail2 re-expression and cranial neural crest differentiation in Xenopus

During vertebrate embryogenesis, the cranial neural crest (CNC) forms at the neural plate border and subsequently migrates and differentiates into many types of cells. The transcription factor Snail2, which is induced by canonical Wnt signaling to be expressed in the early CNC, is pivotal for CNC induction and migration in Xenopus. However, snail2 expression is silenced during CNC migration, and its roles at later developmental stages remain unclear. We generated a transgenic X. tropicalis line that expresses enhanced green fluorescent protein (eGFP) driven by the snail2 promoter/enhancer, and observed eGFP expression not only in the pre-migratory and migrating CNC, but also the differentiating CNC. This transgenic line can be used directly to detect deficiencies in CNC development at various stages, including subtle perturbation of CNC differentiation. In situ hybridization and immunohistochemistry confirm that Snail2 is reexpressed in the differentiating CNC. Using a separate transgenic Wnt reporter line, we show that canonical Wnt signaling is also active in the differentiating CNC. Blocking Wnt signaling shortly after CNC migration causes reduced snail2 expression and impaired differentiation of CNC-derived head cartilage structures. These results suggest that Wnt signaling drives the reexpression of snail2 in the post-migratory CNC and regulates CNC differentiation.

developmental biology↗

bioRxiv2018

A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients

ASMT is a key determinant of the levels of released melatonin. Though melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles from thousands of patients and found that ASMT expression was significantly lower in breast cancer tumors relative to healthy tissue. Among cancer patients, those with greater expression had better relapse-free survival outcomes and longer metastasis-free survival times, and they also experienced longer periods before relapse or distance recurrence following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promoted cancer cell death by promoting apoptosis. Motivated by these results, we devised an ASMT gene signature that identifies low-risk cases with great accuracy. This signature was validated using both mRNA array and RNAseq datasets. Intriguingly, patients who are classified as high-risk benefit from adjuvant chemotherapy, and those with grade II tumors who are classified as low-risk exhibit improved overall survival and distance relapse-free outcomes following endocrine therapy. Our findings more clearly elucidate the roles of ASMT, provide strategies for improving the efficacy of tamoxifen treatment, and help to identify those patients who may maximally benefit from adjuvant or endocrine therapies.

cancer biology↗

bioRxiv2018

Cooperativity and Avidity in Membrane Binding by C2AB Tandem Domains of Synaptotagmins 1 and 7

Synaptotagmin-1 (Syt-1) and synaptotagmin-7 (Syt-7) contain analogous tandem C2 domains, C2A and C2B, which together serve as a Ca2+ sensor to bind membranes and promote the stabilization of exocytotic fusion pores. Functionally, Syt-1 triggers fast release of neurotransmitters, while Syt-7 is involved in lower-Ca2+ processes such as hormone secretion. Evidence suggests that Syt-1 C2 domains bind membranes cooperatively, penetrating farther into membranes as the C2AB tandem than as individual C2 domains. In contrast, we previously reported that the two C2 domains of Syt-7 bind membranes independently, based in part on measurements of their liposome dissociation kinetics. Here, we have investigated the effects of C2A-C2B interdomain cooperativity with Syt-1 and Syt-7 using directly comparable measurements. We report Ca2+ sensitivities, dissociation kinetics, and membrane insertion using liposomes approximating physiological lipid compositions. Equilibrium Ca2+ titrations confirm that the Syt-7 C2AB tandem has a greater Ca2+ sensitivity of membrane binding than either of its individual domains. Stopped-flow fluorescence kinetic measurements show that Syt-1 C2AB dissociates from liposome membranes much more slowly than either of its isolated C2 domains, suggesting that the two C2 domains of Syt-1 bind membranes cooperatively. In contrast, the dominant population of Syt-7 C2AB has a dissociation rate comparable to its C2A domain, indicating a lack of cooperativity, while only a small subpopulation dissociates at a slower rate. Measurements using an environment-sensitive fluorescent probe indicate that the Syt-7 C2B domain inserts more deeply into membranes as part of the C2AB tandem, similarly to Syt-1. Overall, these measurements are consistent with a model in which the structural linkage of C2A and C2B impacts the membrane-binding geometry of synaptotagmin C2B domains, but imparts little or no cooperativity to Syt-7 membrane binding and dissociation events that are dominated by its C2A domain.

biophysics↗