Biology subjects

Nguyen, T.-V.

Publications and source records attributed to Nguyen, T.-V..

3 recordsLinked to original sources

bioRxiv2022

Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

Obesity is generally associated with insulin resistance in liver and muscle and increased risk of developing type 2 diabetes, however there is a population of obese people that remain insulin sensitive. Similarly, recent work suggests that mice fed high carbohydrate diets can become obese without apparent glucose intolerance. To investigate this phenomenon further, we fed mice either a high fat (Hi-F) or high starch (Hi-ST) diet and measured adiposity, glucose tolerance, insulin sensitivity and tissue lipids compared to control mice fed a standard laboratory chow. Both Hi-ST and Hi-F mice accumulated a similar amount of fat and tissue triglyceride compared to chow-fed mice. However while Hi-F diet mice developed glucose intolerance as well as liver and muscle insulin resistance (assessed via euglycemic/hyperinsulinemic clamp), obese Hi-ST mice maintained glucose tolerance and insulin action similar to lean, chow-fed controls. This preservation of insulin action despite obesity in Hi-ST mice was associated with differences in de novo lipogenesis and levels of C22:0 ceramide in liver and C18:0 ceramide in muscle. This indicates that dietary manipulation can influence insulin action independently of the level of adiposity and that the presence of specific ceramide species correlate with these differences.

physiology↗

bioRxiv2019

Cell numbers, distribution, shape, and regional variation throughout the murine hippocampal formation from the adult brain Allen Reference Atlas

Quantifying the distribution of cells in every brain region is fundamental to attaining a comprehensive census of distinct neuronal and glial types. Until recently, estimating neuron numbers involved time-consuming procedures that were practically limited to stereological sampling. Progress in open-source image recognition software, growth in computing power, and unprecedented neuroinformatics developments now offer the potentially paradigm-shifting alternative of comprehensive cell-by-cell analysis in an entire brain region. The Allen Brain Atlas provides free digital access to complete series of raw Nissl-stained histological section images along with regional delineations. Automated cell segmentation of these data enables reliable and reproducible high-throughput quantification of regional variations in cell count, density, size, and shape at whole-system scale. While this strategy is directly applicable to any regions of the mouse brain, we first deploy it here on the closed-loop circuit of the hippocampal formation: the medial and lateral entorhinal cortices; dentate gyrus (DG); areas Cornu Ammonis 3 (CA3), CA2, and CA1; and dorsal and ventral subiculum. Using two independent image processing pipelines and the adult mouse reference atlas, we report the first cellular-level soma segmentation in every sub-region and layer of the left hippocampal formation through the full rostral-caudal extent, except for the (already well characterized) principal layers of CA and DG. The overall numbers ([~]600k cells in entorhinal cortex, [~]200k in DG, [~]430k in CA1-3, and [~]290k in subiculum) are corroborated by traditional stereological sampling on a data subset and well match sparse published reports.

neuroscience↗

bioRxiv2017

Double Maternal Effect: Duplicated Nucleoplasmin 2 Genes, npm2a And npm2b, Are Shared By Fish And Tetrapods, And Have Distinct And Essential Roles In Early Embryogenesis

Nucleoplasmin 2 (npm2) is an essential maternal-effect gene that mediates early embryonic events through its function as a histone chaperone that remodels chromatin. Here we report the existence of two npm2 (npm2a and npm2b) genes in zebrafish. We examined the evolution of npm2a and npm2b in a variety of vertebrates, their potential phylogenetic relationships, and their biological functions using knockout models via the CRISPR/cas9 system. We demonstrated that the two npm2 duplicates exist in a wide range of vertebrates, including sharks, ray-finned fish, amphibians, and sauropsids, while npm2a was lost in Coelacanth and mammals, as well as some specific teleost lineages. Using phylogeny and synteny analyses, we traced their origins to the early stages of vertebrate evolution. Our findings suggested that npm2a and npm2b resulted from an ancient local gene duplication, and their functions diverged although key protein domains were conserved. We then investigated their functions by examining their tissue distribution in a wide variety of species and found that they shared ovarian-specific expression, a key feature of maternal-effect genes. We also showed that both npm2a and npm2b are maternally-inherited transcripts in vertebrates. Moreover, we used zebrafish knockouts to demonstrate that npm2a and npm2b play essential, but distinct, roles in early embryogenesis. npm2a functions very early during embryogenesis, at or immediately after fertilization, while npm2b is involved in processes leading up to or during zygotic genome activation. These novel findings will broaden our knowledge on the evolutionary diversity of maternal-effect genes and underlying mechanisms that contribute to vertebrate reproductive success.\n\nAuthor SummaryThe protein and transcript of the npm2 gene have been previously demonstrated as maternal contributions to embryos of several vertebrates. Recently, two npm2 genes, denoted here as npm2a and npm2b, were discovered in zebrafish. This study was conducted to explore the evolutionary origin and changes that occurred that culminated in their current functions. We found that an ancient local duplication of the ancestral npm2 gene created the current two forms, and while most vertebrates retained both genes, notably, mammals and certain species of fish lost npm2a and, albeit rarely, both npm2a and npm2b. Our functional analyses showed that npm2a and npm2b have diverse but essential functions during embryogenesis, as npm2a mutants failed to undergo development at the earliest stage while npm2b mutants developed, although abnormally, until the zygotic genome activation stage after which their development was arrested followed subsequently by death. Our study is the first to clearly demonstrate the evolution, diversification, and functional analyses of the npm2 genes, which are essential maternal factors that are required for proper embryonic development and survival.

evolutionary biology↗