Biology subjects

Tran, N. D.

Publications and source records attributed to Tran, N. D..

5 recordsLinked to original sources

bioRxiv2025

Epi4Ab: A data-driven prediction model of conformational epitopes for specific antibody VH/VL families and CDR H3/L1 sequences.

Antibodies recognize antigens via complementary and structurally dependent mechanisms. Therefore, inclusion of antibody inputs is crucial for accurate epitope prediction. Given limited availability of antibody-antigen complex structures, it is necessary that any epitope prediction model requires minimal yet sufficient antibody inputs to ensure precise epitope identification. To address this need, we introduce Epi4Ab, an antibody-specific epitope prediction model, which focuses on identifying unique in-contact antigen residues for a given antibody. Epi4Ab requires minimal antibody inputs, specifically VH/VL families and CDR H3/L1 sequences.

bioinformatics↗

bioRxiv2023

Human induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation

Assisted reproductive technologies (ART) have significantly impacted fertility treatment worldwide through innovations such as in vitro fertilization (IVF) and in vitro maturation (IVM). IVM holds promise as a technology for fertility treatment in women who cannot or do not wish to undergo conventional controlled ovarian stimulation (COS). However, IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity. Furthermore, recently reported novel IVM approaches are limited to use in cycles lacking human chorionic gonadotropin (hCG) triggers, which is not standard practice in fertility treatment. We recently reported the development of ovarian support cells (OSCs) generated from human induced pluripotent stem cells (hiPSCs) that recapitulate dynamic ovarian function in vitro. Here we investigate the potential of the se OSCs in an IVM co-culture system to improve the maturation of human cumulus-enclosed immature oocytes retrieved from abbreviated gonadotropin stimulated cycles. We reveal that OSC-IVM significantly improves maturation rates compared to existing IVM systems. Most importantly, we demonstrate that OSC-assisted IVM oocytes are capable of significantly improving euploid blastocyst formation and yielding blastocysts with normal global and germline differential methylation region methylation profiles, a key marker of their clinical utility. Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. Structured AbstractO_ST_ABSObjectiveC_ST_ABSTo determine if in vitro maturation (IVM) of human oocytes can be improved by co-culture with ovarian support cells (OSCs) derived from human induced pluripotent stem cells (hiPSCs). DesignThree independent experiments were performed in which oocyte donors were recruited to undergo abbreviated gonadotropin stimulation and retrieved cumulus oocyte complexes (COCs) were randomly allocated between the OSC-IVM and control IVM conditions. SubjectsAcross the three experiments, a total of 67 oocyte donors aged 19 to 37 years were recruited for retrieval using informed consent. Anti-mullerian hormone (AMH) value, antral follicle count (AFC), age, BMI, and ovarian pathology were used for inclusion and exclusion criteria. Intervention and ControlThe OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture supplemented with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione and doxycycline. IVM controls comprised commercially-available IVM media without OSCs and contained either the same supplementation as above (media-matched control), or FSH and hCG only (IVM media control). In one experiment, an additional control using fetal ovarian somatic cells (FOSCs) was used with the same cell number and media conditions as in the OSC-IVM. Main Outcome MeasuresPrimary endpoints consisted of metaphase II (MII) formation rate and oocyte morphological quality assessment. A limited cohort of oocytes were utilized for secondary endpoints, consisting of fertilization and blastocyst formation rates with preimplantation genetic testing for aneuploidy (PGT-A) and embryo epigenetic analysis. ResultsOSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the media-matched control, a commercially available IVM media control, and the FOSC-IVM control. Oocyte morphological quality between OSC-IVM and controls did not significantly differ. OSC-IVM displayed a trend towards improved fertilization, cleavage, and blastocyst formation. OSC-IVM showed statistically significant improvement in euploid day 5 or 6 blastocyst formation compared to the commercially available IVM media control. OSC-IVM embryos displayed similar epigenetic global and germline loci profiles compared to conventional stimulation and IVM embryos. ConclusionThe novel OSC-IVM platform is an effective tool for maturation of human oocytes obtained from abbreviated gonadotropin stimulation cycles, supporting/inducing robust euploid blastocyst formation. OSC-IVM shows broad utility with different stimulation regimens, including hCG triggered and untriggered oocyte retrieval cycles, making it a highly useful tool for modern fertility treatment.

developmental biology↗

bioRxiv2021

N-myc Downstream Regulated Gene 1 (NDRG1) functions as a molecular switch for cellular adaptation to hypoxia

Lack of oxygen (hypoxia and anoxia) is detrimental to cell function and survival and underlies many disease conditions. Hence, metazoans have evolved mechanisms to adapt to low oxygen. One such mechanism, metabolic suppression, decreases the cellular demand for oxygen by downregulating ATP-demanding processes. However, the molecular mechanisms underlying this adaptation are poorly understood. Here, we report on the role of ndrg1a in hypoxia adaptation of the anoxia-tolerant zebrafish embryo. ndrg1a is expressed in the kidney and ionocytes, cell types that use large amounts of ATP to maintain ion homeostasis. ndrg1a mutants are viable and develop normally when raised under normal oxygen. However, their survival and kidney function is reduced relative to WT embryos following exposure to prolonged anoxia. We further demonstrate that Ndrg1a binds to the energy-demanding sodium-potassium ATPase (NKA) pump under anoxia and is required for its degradation, which may preserve ATP in the kidney and ionocytes and contribute to energy homeostasis. Lastly, we show that sodium azide treatment, which increased lactate levels, was sufficient to trigger NKA degradation in an Ndrg1a-dependent manner. These findings support a model whereby Ndrg1a is essential for hypoxia adaptation and functions downstream of lactate signaling to induce NKA degradation, a process known to conserve cellular energy.

developmental biology↗

bioRxiv2021

The within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on within-host virus diversity of infections in otherwise healthy adults based on single timepoint data. Here, we analysed the within-host evolution of 82 longitudinally-sampled individuals, mostly young children, infected with A/H3N2 or A/H1N1pdm09 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous changes were common early in infection but decreased or remained constant throughout infection. For A/H3N2 viruses, early infection was dominated by purifying selection. However, as infections progressed, nonsynonymous variants increased in frequencies even though within-host virus titres decreased, leading to the maintenance of virus diversity via mutation-selection balance. Our findings suggest that this maintenance of genetic diversity in these children combined with their longer duration of infection may provide important opportunities for within-host virus evolution.

microbiology↗

bioRxiv2020

High-surety isothermal amplification and detection of SARS-CoV-2, including with crude enzymes

ABSTRACTIsothermal nucleic acid amplification tests (iNAT), such as loop-mediated isothermal amplification (LAMP), are good alternatives to polymerase chain reaction (PCR)-based amplification assays, especially for point-of-care and low resource use, in part because they can be carried out with relatively simple instrumentation. However, iNATs can generate spurious amplicons, especially in the absence of target sequences, resulting in false positive results. This is especially true if signals are based on non-sequence-specific probes, such as intercalating dyes or pH changes. In addition, pathogens often prove to be moving, evolving targets, and can accumulate mutations that will lead to inefficient primer binding and thus false negative results. Internally redundant assays targeting different regions of the target sequence can help to reduce such false negatives. Here we describe rapid conversion of three previously described SARS-CoV-2 LAMP assays that relied on non-sequence-specific readout into assays that can be visually read using sequence-specific fluorogenic oligonucleotide strand exchange (OSD) probes. We evaluate one-pot operation of both individual and multiplex LAMP-OSD assays and demonstrate detection of SARS-CoV-2 virions in crude human saliva.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗