Biomedical subjects

Jennifer Nguyen

Publications and source records attributed to Jennifer Nguyen.

3 recordsLinked to original sources

PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗

PubMed2006

Experimental verification of theoretical predictions concerning the optimum defibrillation waveform.

The efficacy of electrical therapy at terminating ventricular fibrillation is highly dependent on the waveform used. We present experimental results which test one theory for defibrillation waveform dependence. Forty-four defibrillation waveforms (22 monophasic, 22 biphasic) were designed according to the theoretical construct of Fishier (2000). The waveforms were then tested on 67 male guinea pigs (46 for monophasic, 21 for biphasic waveforms) using a custom designed defibrillator and 12-mm subcutaneous disc electrodes. There was considerable agreement between the theoretical and experimental results. For example, as predicted, the ascending exponential waveform of 1 ms proved to be the most effective (86.4%) monophasic waveform, where efficacy is the number of successful shocks divided by the total number delivered. In addition, the efficacy decrease with duration increase was accurately predicted by the model for monophasic waveforms. For biphasic waveforms, as predicted by the model, when the first phase was optimized, an increase in second phase duration caused an increase in defibrillation efficacy (10 of 11 tested duration pairs). We conclude that the theoretical framework adequately explains the mechanism by which the defibrillation waveform affects efficacy for monophasic waveforms and, in at least one aspect, biphasic waveforms.

Animals↗

PubMed2003

Smad signaling in mesenchymal and chondroprogenitor cells.

BACKGROUND: Bone morphogenetic proteins (BMPs) are pleiotropic differentiation factors that regulate cell fate determination by orchestrating the activities of downstream signal transducers. Although BMP ligands can elicit signal transduction from heterodimeric combinations of several type-I and type-II receptors, cytoplasmic transducers of the BMP signal include only three known BMP-specific regulatory Smad proteins: Smad1, 5, and 8. In order to determine the combination of signals that regulate chondrogenesis by BMPs, we analyzed the functions of BMP Smad subtypes. METHODS: Multipotential mesenchymal C3H10T1/2 cells and monopotential chondroprogenitor MC615 cells were placed in micromass culture in the presence or absence of BMP4. Chondrogenic differentiation was assayed by measuring Sox9 and type-II collagen gene expression and by alcian blue staining. Transactivation of type-II collagen by regulatory Smads singly, or in combination with Smad4, which partners with regulatory Smads, was assayed by luciferase activity. RESULTS: In the absence of BMP4, mesenchymal cells did not exhibit chondrogenic differentiation, whereas chondroprogenitor cells showed increased cartilage marker expression. In the presence of BMP4, the rate and extent of chondrogenesis increased in a dose-dependent manner for both cell types. We further determined that Smad1 or Smad5, but not Smad8, synergized with Smad4 in the transactivation of the type-II collagen promoter in chondroprogenitor cells. In contrast, Smad8 and Smad4 presented modest synergy in mesenchymal cells. CONCLUSIONS: Taken together, our data suggest that uncommitted mesenchymal cells do not have the cellular competence to respond to the rate-limiting chondroinductive factor BMP. However, in chondroprogenitor cells, BMP stimulates differentiation through mechanisms mediated by Smad1 or Smad5 in combination with Smad4.

Animals↗