Biology subjects

Nguyen, T. M.

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

23 records · Page 2Linked to original sources

bioRxiv2020

Polar Gini Curve: a Technique to Discover Single-cell Biomarker Using 2D Visual Information

In this work, we design the Polar Gini Curve (PGC) technique, which combines the gene expression and the 2D embedded visual information to detect biomarkers from single-cell data. Theoretically, a Polar Gini Curve characterizes the shape and evenness of cell-point distribution of cell-point set. To quantify whether a gene could be a marker in a cell cluster, we can combine two Polar Gini Curves: one drawn upon the cell-points expressing the gene, and the other drawn upon all cell-points in the cluster. We hypothesize that the closers these two curves are, the more likely the gene would be cluster markers. We demonstrate the framework in several simulation case-studies. Applying our framework in analyzing neonatal mouse heart single-cell data, the detected biomarkers may characterize novel subtypes of cardiac muscle cells. The source code and data for PGC could be found at https://figshare.com/projects/Polar_Gini_Curve/76749.

bioinformatics↗

bioRxiv2019

Prenatal alcohol exposure programs offspring disease: Impacts on metabolic health and dietary preference in a rat model of acute exposure

Alcohol consumption is highly prevalent amongst women of reproductive age. Given that approximately 50% of pregnancies are unplanned, alcohol has the potential to affect fetal development and program chronic disease in offspring. We examined the effect of an acute but moderate prenatal alcohol exposure (PAE) on glucose metabolism, lipid levels and dietary preference in adolescent and/or adult rat offspring. Pregnant Sprague-Dawley rats received an oral gavage of ethanol (1g/kg maternal body weight, n=9 dams) or an equivalent volume of saline (control, n=8 dams) at embryonic days 13.5 and 14.5. PAE resulted in a blood alcohol concentration of 0.05-0.06% 1h post-gavage in dams. Fasting blood glucose concentration was not affected by PAE in offspring at any age, nor were blood glucose levels during a glucose tolerance test (GTT) in 6-month old offspring (P>0.5). However, there was evidence of insulin resistance in PAE male offspring at 6 months of age, with significantly elevated fasting plasma insulin (P = 0.001), a tendency for increased first phase insulin secretion during the GTT and impaired glucose clearance following an insulin challenge (P = 0.007). This was accompanied by modest alterations in protein kinase B (AKT) signalling in adipose tissue. PAE also resulted in reduced calorie consumption by offspring compared to controls (P = 0.04). These data suggest that a relatively low-level, acute PAE programs metabolic dysfunction in offspring in a sex-specific manner. These results highlight that alcohol consumption during pregnancy has the potential to affect the long-term health of offspring.\n\nKey points summaryO_LIPrenatal alcohol exposure has the potential to affect fetal development and program chronic disease in offspring.\nC_LIO_LIPrevious preclinical models typically use high, chronic doses of alcohol throughout pregnancy to examine effects on offspring, particularly on the brain and behaviour.\nC_LIO_LIIn this study we use a rat model of moderate, acute, prenatal alcohol exposure to determine if this can be detrimental to maintenance of glucose homeostasis in adolescent and adult offspring.\nC_LIO_LIAlthough female offspring were relatively unaffected, there was evidence of insulin resistance in 6-month old male offspring exposed to prenatal alcohol, suggestive of a pre-diabetic state.\nC_LIO_LIThis result suggests that even a relatively low-dose, acute exposure to alcohol during pregnancy can still program metabolic dysfunction in a sex-specific manner.\nC_LI

developmental biology↗

bioRxiv2019

Segregostat: A novel concept to control phenotypic diversification dynamics on the example of Gram-negative bacteria

Controlling and managing the degree of phenotypic diversification of microbial populations is a challenging task. This task not only requires detailed knowledge regarding diversification mechanisms but also advances technical setups for the real-time analyses and control of population behavior on single-cell level. In this work, setup, design and operation of the so called segregostat is described which, in contrast to a traditional chemostats, allows the control of phenotypic diversification of microbial populations over time. Two exemplary case studies will be discussed, emphasizing the applicability and versatility of the proposed approach. In detail the phenotypic diversification of Eschericia coli or Pseudomonas putida based on monitoring membrane permeability will be controlled. We show that upon nutrient limitation, cell population tends to diversify into several subpopulations exhibiting distinct phenotypic (non-permeablized and permeablized cells). On-line analysis leads to the determination of the ratio between cells in these two states, which in turn trigger the addition of glucose pulses in order to maintain a pre-defined diversification ratio. These results prove that phenotypic diversification can be controlled by means of defined pulse-frequency modulation within continuously running bioreactor setups. This lays the foundation for systematic studies, not only of phenotypic diversification but also for all processes where dynamics single cell approaches are required, such as synthetic co-culture processes.

microbiology↗

bioRxiv2017

MULTILOCUS SEQUENCE TYPING REVEALS A UNIQUE CO-DOMINANT POPULATION STRUCTURE OF CRYPTOCOCCUS NEOFORMANS VAR. GRUBII IN VIETNAM

Cryptococcosis is amongst the most important invasive fungal infections globally, with cryptococcal meningitis causing an estimated 180,000 deaths each year in HIV infected patients alone. Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii (serotype A, molecular type VNI) has a global distribution and is responsible for the majority of cases. Here, we used the consensus ISHAM Multilocus Sequence Typing (MLST) for C. neoformans to define the population structure of clinical isolates of Cryptococcus neoformans var. grubii from Vietnam (n=136) and Laos (n=81). We placed these isolates into the global context using published MLST data from 8 other countries (total N = 669). We observed a phylo-geographical relationship in which Laos was similar to its Southeast Asian neighbor Thailand in being dominated (83%) by Sequence Type (ST) 4 and its Single Locus Variant ST6. On the other hand, Vietnam was uniquely intermediate between Southeast Asia and East Asia having both ST4/ST6 (35%) and ST5 (48%) which causes the majority of cases in East Asia. Analysis of genetic distance (Fst) between different populations of Cryptococcus neoformans var. grubii supported the intermediate nature of the population from Vietnam. A strong association between ST5 and infection in apparently immunocompetent, HIV-uninfected patients was observed in Vietnam (OR: 7.97, [95%CI: 3.18-19.97], p < 0.0001). Our study emphasizes that Vietnam, with its intermediate Cryptococcus neoformans var. grubii population structure, provides the strongest epidemiological evidence of the relationship between ST5 and infection of HIV-uninfected patients. Human population genetic distances within the region suggest these differences in CNVG population across Southeast Asia are driven by ecological factors rather than host factors.\n\nAuthor summaryCryptococcus neoformans is a yeast that causes meningitis in people, usually with damaged immune systems. There are >180,000 deaths in HIV-infected patients each year, most occurring where there are the highest HIV/AIDS disease burdens. Vietnam and Laos have contributed significantly to clinical trials aiming to improve the treatment of cryptococcal meningitis, but the relationship of isolates from these countries to the global population is not yet described. Here, we address this knowledge gap by using Multilocus Sequence Typing to study the population of Cryptococcus neoformans var. grubii (CNVG) in Laos and Vietnam, with the specific aim of incorporating these populations into the wider global context. We found that, in most countries, a single lineage (family) of strains was responsible for most disease. The Vietnamese CNVG population was unusual in that 2 main lineages circulated at the same time. The Vietnamese CNVG population occupies a middle ground between Thailand/Laos in the west and China in the east. The differences in population structure moving from West to East are probably due to ecological differences. Disease in HIV uninfected patients was almost always due to members of a single family of strains (ST5).

molecular biology↗

bioRxiv2017

N VITRO AND IN VIVO CHARACTERISATION OF ISOLATES OF CRYPTOCOCCUS NEOFORMANS CAUSING MENINGITIS IN HIV-INFECTED AND UNINFECTED PATIENTS IN VIETNAM

We previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising in HIV-uninfected individuals. This disease was associated with a single genotype of Cryptococcus neoformans (Sequence Type (ST)5), which was significantly less common in HIV-infected individuals. Aiming to compare the phenotypic characteristics of ST5 and non-ST5 C. neoformans we selected 30 representative Vietnamese isolates, compared their in vitro pathogenic potential and in vivo virulence. ST5 and non-ST5 organisms exhibited comparable characteristics with respect to in vitro virulence markers including melanin production, replication at 37{degrees}C, and growth in cerebrospinal fluid. However, the ST5 isolates had significantly increased variability in cellular and capsular sizing compared with non-ST5 organisms (p<0.001). Counter-intuitively, mice infected with ST5 isolates had significantly longer survival with lower fungal burdens at day 7 than non-ST5 isolates. Notably, ST5 isolates induced significantly greater initial inflammatory responses than non-ST5 strains, measured by TNF- concentrations (p<0.001). Despite being generally less virulent in the mouse model, we hypothesize that the significant within strain variation seen in ST5 isolates in the tested phenotypes may represent an evolutionary advantage enabling adaptation to novel niches including apparently immunocompetent human hosts.

microbiology↗