Biology subjects

Nguyen, T. L.

Publications and source records attributed to Nguyen, T. L..

15 recordsLinked to original sources

bioRxiv2026

Resilience of multispecies biofilm communities: Comparative analysis of a Veillonella dispar-dominant oral biofilm under diverse oxygen conditions in vitro

Oral multispecies biofilms developing on dental implants drive peri-implant mucositis and peri-implantitis. They are shaped by the physicochemical conditions of their surrounding environment, among which oxygen availability is an important influential factor. However, while oxygen tension fluctuates significantly within the peri-implant pocket, whether these environmental shifts are sufficient to influence the structure and composition of an established microbial community remains unclear. For this purpose, we evaluated the structure and composition of a four-species oral biofilm model comprising the species Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar and Porphyromonas gingivalis, which was cultivated under normoxic (21% O2), hypoxic (1% O2) and anoxic (0% O2;) conditions for a period of 21 days. Biofilm 3D architecture, volume and membrane integrity was analyzed by LIVE/DEAD staining combined with confocal laser scanning microscopy. Community composition was assessed by quantitative real-time PCR and complemented by Fluorescence In Situ Hybridization (FISH) to provide structural context. While normoxia transiently promoted higher early biofilm volume and membrane integrity, the community exhibited remarkable long-term resilience, consistently maintaining a V. dispar-dominated structure across all oxygen gradients. Crucially, the obligate anaerobic pathogen P. gingivalis persisted as a viable minority (~1%) even under 21-day normoxic cultivation, sheltered within the deeper layers of the biofilm. These results suggest that clinical oxygen levels alone are not able to drastically modulate established oral biofilm communities and that oxygen-sensitive pathogens persist in a subclinical sanctuary protected by the surrounding non-pathogenic species.

microbiology↗

bioRxiv2025

Environmental and vector detection of African swine fever virus DNA in Vietnam: Evidence for potential transmission through wastewater and Amblyomma javanense ticks

African swine fever virus (ASFV) remains a major global threat to pig production, yet its environmental and vector reservoirs in Southeast Asia are poorly understood. This study provides the first evidence in Southeast Asia indicating that ASFV DNA can be detected in pig farm wastewater and that Amblyomma javanense ticks may act as potential mechanical carriers of the virus in natural settings. To elucidate part of the environmental dynamics and possible transmission routes of ASFV, we developed and applied a highly sensitive polyethylene glycol (PEG) precipitation-based real-time PCR method specifically for wastewater surveillance, as the viral load in aquatic environments is presumed to be substantially lower than that in arthropod vectors. A total of 40 tick samples and 93 wastewater samples were analyzed. ASFV DNA was identified in 3 of 40 ticks (7.5%) and 7 of 93 wastewater samples (7.5%). The developed method showed a 100-fold improvement in analytical sensitivity, lowering Ct values by 3-7 cycles and increasing the detection rate from 3.2% to 7.5% compared with the reference method. Diagnostic sensitivity and specificity for wastewater testing were 100.0% and 95.6%, respectively. Although infectious virus was not recovered from ASFV-positive wastewater samples, control experiments confirmed that PEG treatment did not interfere with viral infectivity. These findings highlight the potential role of environmental and tick-mediated transmission in ASF epidemiology and provide a practical tool for early warning and post-outbreak monitoring of ASFV in endemic regions.

microbiology↗

bioRxiv2025

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO): building local capacity in genomics, bioinformatics, and precision medicine

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO) aims to build a community of Colombian researchers in support of local capacity in genomics, bioinformatics, and precision health. Here, we present the first CODIGO data release and the consortium web platform, including annotations for more than 95 million genetic variants from 1,441 samples representing 14 populations from across the country. CODIGO samples show a wide range of African (16.7%), European (50.6%), and Indigenous American (32.8%) genetic ancestry components, with five distinct ancestry clusters. Thousands of ancestry-enriched variants, with divergent allele frequencies across clusters, show pharmacogenomic and clinical genetic associations. Examples include African ancestry-enriched variants associated with fast metabolism of the immunosuppressive drug tacrolimus and malaria resistance and European ancestry-enriched variants associated with nicotine dependence and hereditary hemochromatosis. CODIGO reveals the nexus between ancestry and health in Colombia and underscores the utility of collaborative genome sequence analysis efforts.

genomics↗

bioRxiv2024

Tensor Kernel Learning for Classification of Alzheimer's Conditions using Multimodal Data

Early, timely, and accurate assessment of Alzheimers disease (AD), particularly at its earlier stage - mild cognitive impairment (MCI) -, is central to detecting, managing, and potentially treating the disease. The biological underpinnings of AD, however, is multifaceted, from genetic variations, abnormal protein accumulation, to irregular brain functions and structure. A joint analysis of these data, therefore, may offer potentially new insights about AD-related biomarkers and AD prediction. But such explorations must confront the complexity of these data: heterogeneity, multimodality and high-dimensionality. Here, to address these challenges, we propose a new machine-learning method, namely the tensor kernel learning (TKL), leveraging tensor methods and kernel learning, to enhance AD assessment by enhancing multi-modal data integration. More specifically, TKL first uses CP/PARAFAC decomposition and graph diffusion to fuse multiple kernels learned from four complementary data modalities (MRI, PET, CSF, and SNP data). We then used a supervised kernel for a kernel SVM classifier to identify potential patients. To evaluate the effectiveness of TKL, we apply it to data from the Alzheimers Disease Neuroimaging Initiative (ADNI; the sample size n = 331 subjects), including cognitively normal individuals (CN), MCI subjects, and AD patients. TKL improves AD classification performance in both linear and nonlinear combinations, achieving accuracies of 91.31% for CN vs. AD, 81.45% for CN vs. MCI, and 78.27% for AD vs. MCI, compared to 85.48%, 70.89%, and 73.51% using the best single modality. Additionally, TKL reveals clearer, more structured patterns in the data, enhancing interpretation and understanding of the relationships among different modalities. Detailed implementation details of our method can be found at: https://github.com/thanhvd18/Tensor-Kernel-Learning-matlab.

neuroscience↗

bioRxiv2023

Interneuron migration defects during corticogenesis contribute to Dyrk1a haploinsufficiency syndrome pathogenesis via actomyosin dynamics deregulations

Interneuron development is a crucial step of brain corticogenesis. When affected it often leads to brain dysfunctions, such as epilepsy, intellectual disabilities and autism spectrum disorder. Such defects are observed in the DYRK1A-haploinsufficiency syndrome, caused by mutations of DYRK1A, and commonly associated to cortical excitatory/inhibitory imbalance. However, how this imbalance is established in this syndrome remains elusive. Here, using mouse models and live imaging, we show that Dyrk1a specifically regulates the development of the cortical GABAergic system. Unlike projection excitatory neurons, we demonstrate that interneuron tangential migration relies on Dyrk1a dosage and kinase activity through a mechanism involving actomyosin cytoskeleton remodeling. Interestingly, we further demonstrate that mice with heterozygous inactivation of Dyrk1a in interneurons show behavioral defects and epileptic activity, recapitulating phenotypes observed in human patients. Altogether, these data highlight the critical role of Dyrk1a in the development of the GABAergic system and the pathophysiology of DYRK1A-haploinsufficiency syndrome.

developmental biology↗

bioRxiv2022

The Influences of Stomatal Size and Density on Rice Drought, Salinity and VPD Resilience

O_LIA warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice yields (Oryza sativa L.). Elevated temperatures are causing vapour pressure deficit (VPD) rises, leading to stomata closure, further reducing plant productivity and cooling. It is unclear which conformation of stomatal size (SS) and stomatal density (SD) will best suit these future environmental extremes. C_LIO_LITo understand the influence of stomatal characteristics on rice abiotic stress tolerance, we screened the stomatal characteristics of 72 traditionally-bred varieties. We found significant variation in SS, SD and maximal stomatal conductance (gsmax) but did not identify any varieties with SD and gsmax as low as the genetically manipulated stomatal development mutant OsEPF1oe. C_LIO_LITraditionally-bred varieties with high SD and small SS (resulting in high gsmax) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties tested were as resilient to drought or salinity as low SD OsEPF1oe mutants. High SD and small SS rice displayed faster stomatal closure during rising VPD, but photosynthesis and plant cooling were reduced. C_LIO_LICompromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses. C_LI

plant biology↗

bioRxiv2021

High-speed live cell interferometry for screening bioprinted organoids

High-throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms for high-throughput screening use two-dimensional cultures of immortalized cell lines which do not accurately reflect the biology of human tumors. More clinically relevant model systems, such as three-dimensional tumor organoids, can be difficult to screen and scale. For example, manually seeded organoids coupled to destructive endpoint assays allow for the characterization of response to treatment, but do not capture the transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We therefore developed a pipeline to generate bioprinted tumor organoids linked to label-free, real-time imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D organoid structures that preserve tumor histology and gene expression. HSLCI imaging in tandem with machine learning-based image segmentation and organoid classification tools enables accurate, label-free parallel mass measurements for thousands of bioprinted organoids. We demonstrate that our method quantitatively identifies individual organoids as insensitive, transiently sensitive, or persistently sensitive to specific treatments. This opens new avenues for rapid, actionable therapeutic selection using automated tumor organoid screening.

bioengineering↗

bioRxiv2021

Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome

Perturbation of the excitation/inhibition (E/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Mutation in the DYRK1A gene located on human chromosome 21 (Hsa21) leads to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles (MRD7). Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS). Dyrk1a is expressed in both glutamatergic and GABAergic neurons, but its impact on each neuronal population has not yet been elucidated. Here we investigated the impact of Dyrk1a gene copy number variation in glutamatergic neurons using a conditional knockout allele of Dyrk1a crossed with the Tg(Camk2-Cre)4Gsc transgenic mouse. We explored this genetic modification in homozygotes, heterozygotes and combined with the Dp(16Lipi-Zbtb21)1Yey trisomic mouse model to unravel the consequence of Dyrk1a dosage from 0 to 3, to understand its role in normal physiology, and in MRD7 and DS. Overall, Dyrk1a dosage in glutamatergic neurons did not impact locomotor activity, working memory or epileptic susceptibility, but revealed that Dyrk1a is involved in long-term explicit memory. Molecular analyses pointed at a deregulation of transcriptional activity through immediate early genes and a role of DYRK1A at the glutamatergic post-synapse by deregulating and interacting with key post-synaptic proteins implicated in mechanism leading to long-term enhanced synaptic plasticity. Altogether, our work gives important information to understand the action of DYRK1A inhibitors and have a better therapeutic approach. Author summaryThe Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A, DYRK1A, drives cognitive alterations with increased dose in Down syndrome (DS) or with reduced dose in mental retardation disease 7 (MRD7). Here we report that specific and complete loss of Dyrk1a in glutamatergic neurons induced a range of specific cognitive phenotypes and alter the expression of genes involved in neurotransmission in the hippocampus. We further explored the consequences of Dyrk1a dosage in glutamatergic neurons on the cognitive phenotypes observed respectively in MRD7 and DS mouse models and we found specific roles in long-term explicit memory with no impact on motor activity, short-term working memory, and susceptibility to epilepsy. Then we demonstrated that DYRK1A is a component of the glutamatergic post-synapse and interacts with several component such as NR2B and PSD95. Altogether our work describes a new role of DYRK1A at the glutamatergic synapse that must be considered to understand the consequence of treatment targeting DYRK1A in disease.

neuroscience↗

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

Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation and reduces ventilation-induced lung injury in a respiratory distress model

In the neonatal (NRDS) and acute (ARDS) respiratory distress syndromes, mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T-lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 ml/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, over 4 hrs, we support the rats with protective ventilation - VT of 6 ml/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non-T-altering fluorescein (targeting 27 M in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period we sacrifice the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio (W/D), both to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. Sulforhodamine B administration improves oxygenation, reduces W/D and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress. New and NoteworthySulforhodmaine B lowers T. Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier, reduces T specifically in injured lung regions, improves oxygenation and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.

physiology↗

bioRxiv2020

Sulforhodamine B and exogenous surfactant effects on alveolar surface tension in acute respiratory distress syndrome models

In the acute respiratory distress syndrome (ARDS), alveolar surface tension, T, may be elevated. Elevated T should increase ventilation-induced lung injury. Exogenous surfactant therapy, intended to lower T, has not reduced mortality. Sulforhodamine B (SRB) might, alternatively, be employed to lower T. We test whether substances suspected of elevating T in ARDS raise T in the lungs and test the abilities of exogenous surfactant and SRB to reduce T. In isolated rat lungs, we micropuncture a surface alveolus and instill a solution of a purported T-raising substance: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and exogenous surfactant; or with albumin and SRB. We determine T in situ in the lungs by combining servo-nulling pressure measurement with confocal microscopy, and applying the Laplace relation. With control saline, albumin does not alter T, additional surfactant raises T and additional SRB lowers T. The experimental substances, without or with albumin, raise T. Excepting under aspiration conditions, addition of surfactant or SRB lowers T. Exogenous surfactant activity is concentration and ventilation dependent. Sulforhodamine B, which could be delivered intravascularly, holds promise as an alternative therapeutic. New and NoteworthyIn the acute respiratory distress syndrome (ARDS), lowering surface tension, T, should reduce ventilation injury yet exogenous surfactant has not reduced mortality. We show with direct T-determination in isolated lungs that substances suggested to elevate T in ARDS indeed raise T, and exogenous surfactant reduces T. Further, we extend our previous finding that sulforhodamine B (SRB) reduces T below normal in healthy lungs and show that SRB, too, reduces T under ARDS conditions.

physiology↗

bioRxiv2018

Genome-wide association study of peripheral blood DNA methylation and conventional mammographic density measures

Age- and body mass index (BMI)-adjusted mammographie density is one the strongest breast cancer risk factors. DNA methylation is a molecular mechanism that could underlie interindividual variation in mammographic density. We aimed to investigate the association between breast cancer risk-predicting mammographic density measures and blood DNA methylation. For 436 women from the Australian Mammographic Density Twins and Sisters Study and 591 women from the Melbourne Collaborative Cohort Study, mammographic density (dense area, non-dense area and percentage dense area) defined by the conventional brightness threshold was measured using the CUMULUS software, and peripheral blood DNA methylation was measured using the HumanMethylation450 (HM450) BeadChip assay. Associations between DNA methylation at >400,000 sites and mammographic density measures adjusted for age and BMI were assessed within each cohort and pooled using fixed-effect meta-analysis. Associations with methylation at genetic loci known to be associated with mammographic density were also examined. We found no genome-wide significant(P<10-7)association for any mammographic density measure from the meta-analysis, or from the cohort-specific analyses. None of the 299 methylation sites located at genetic loci associated with mammographic density was associated with any mammographic density measure after adjusting for multiple testing (all P>0.05/299 = 1.7 x 10-4). In summary, our study did not detect associations between blood DNA methylation, as measured by the HM450 assay, and conventional mammographic density measures that predict breast cancer risk.

epidemiology↗

bioRxiv2018

Associations between environmental breast cancer risk factors and DNA methylation-based risk-predicting measures

BackgroundGenome-wide average DNA methylation (GWAM) and epigenetic age acceleration have been suggested to predict breast cancer risk. We aimed to investigate the relationships between these putative risk-predicting measures and environmental breast cancer risk factors.\n\nMethodsUsing the Illumina HumanMethylation450K assay methylation data, we calculated GWAM and epigenetic age acceleration for 132 female twin pairs and their 215 sisters. Linear regression was used to estimate associations between these risk-predicting measures and multiple breast cancer risk factors. Within-pair analysis was performed for the 132 twin pairs.\n\nResultsGWAM was negatively associated with number of live births, and positively with age at first live birth (both P<0.05). Epigenetic age acceleration was positively associated with body mass index (BMI), smoking, alcohol drinking and age at menarche, and negatively with age at first live birth (all P<0.05), and the associations with BMI, alcohol drinking and age at first live birth remained in the within-pair analysis.\n\nConclusionsThis exploratory study shows that lifestyle and hormone-related breast cancer risk factors are associated with DNA methylation-based measures that could predict breast cancer risk. The associations of epigenetic age acceleration with BMI, alcohol drinking and age at first live birth are unlikely to be due to familial confounding.

epidemiology↗

bioRxiv2017

Inference about causation between body mass index and DNA methylation in blood from a twin family study

BackgroundSeveral studies have reported DNA methylation in blood to be associated with body mass index (BMI), but only a few have investigated causal aspects of the association. We used a twin family design to assess this association at two life points and applied a novel analytical approach to investigate the evidence for causality.\n\nMethodsThe methylation profile of DNA from peripheral blood was measured for 479 Australian women (mean age 56 years) from 130 twin families. Linear regression was used to estimate the associations of methylation at ~410 000 cytosine-guanine dinucleotides (CpG), and of the average methylation at ~20 000 genes, with current BMI, BMI at age 18-21 years, and the change between the two (BMI change). A novel regression-based methodology for twins, Inference about Causation through Examination of Familial Confounding (ICE FALCON), was used to assess causation.\n\nResultsAt 5% false discovery rate, nine, six and 12 CpGs at 24 loci were associated with current BMI, BMI at age 18-21 years and BMI change, respectively. The average methylation of BHLHE40 and SOCS3 loci was associated with current BMI, and of PHGDH locus was associated with BMI change. From the ICE FALCON analyses with BMI as the predictor and methylation as the outcome, a womans methylation level was associated with her co-twins BMI, and the association disappeared conditioning on her own BMI, consistent with BMI causing methylation. To the contrary, using methylation as the predictor and BMI as the outcome, a womans BMI was not associated with her co-twins methylation level, consistent with methylation not causing BMI.\n\nConclusionFor middle-aged women, peripheral blood DNA methylation at several genomic locations is associated with current BMI, BMI at age 18-21 years and BMI change. Our study suggests that BMI has a causal effect on peripheral blood DNA methylation.

epidemiology↗

bioRxiv2017

In vivo cross-linking and transmembrane helix dynamics support a non-piston model of signaling within E. coli EnvZ

In Gram-negative bacteria, porins span the outer membrane and control the influx of several prominent groups of antibiotics. Thus, it should not be surprising that expression of these porins is often altered in clinical isolates exhibiting multidrug resistance (MDR). The major regulator of porin expression in Escherichia coli is EnvZ, a canonical sensor histidine kinase (SHK). It allosterically processes periplasmic interactions with MzrA and cytoplasmic osmosensing into a single unified change in the ratio of its kinase and phosphatase activities. Unfortunately, the role of the EnvZ transmembrane domain (TMD) in bidirectional communication of these signals remains not well understood. Here, we employed in vivo sulfhydryl-reactivity to probe the dynamics of the TM2 helices and demonstrate that upon stimulus perception, only the region proximal to the periplasm undergoes conformational rearrangement. Furthermore, in silico coarse-grained molecular dynamics (CG-MD) simulations with aromatically tuned variants of EnvZ TM2 demonstrate the existence of both tilting and azimuthal rotational components to transmembrane communication while ruling out piston-type repositioning of TM2. Finally, in contrast to a similar analysis of TM1, we identified position-specific mutants possessing a \"flipped\" phenotype by dual-color fluorescent reporter analysis suggesting that both the periplasmic and cytoplasmic ends of TM2 are critical for maintenance of EnvZ signal output. Taken together, these data strongly support that EnvZ employs a non-piston-type mechanism during transmembrane communication. We conclude by discussing these results within the context of allosteric processing by EnvZ and propose that these results can be used to predict and classify transmembrane communication by various SHKs.\n\nImportanceThe EnvZ sensor histidine kinase serves as the major regulator of porin expression within Escherichia coli. A long-standing question is how stimulus perception by a bacterial receptor on one side of a biological membrane is transmitted to the opposite side of the membrane. To address this question, we monitored the dynamics of the transmembrane domain of EnvZ in vivo and coupled these results with in silico simulations of membrane-embedded EnvZ transmembrane domains. Taken together, these results demonstrate that detection of osmotic stress by the cytoplasmic domain of EnvZ results in non-piston communication across the inner membrane of E. coli. Thus, in addition to understanding how EnvZ regulates porin balance and antibiotic influx, these results contribute to answering the long-standing question of how transmembrane communication is performed by bacterial receptors. Our work concludes with a framework that correlates receptor domain composition and signal transduction mechanisms that could be employed by other research groups on their particular receptors of interest.

biochemistry↗