Biology subjects

Nguyen, V. D.

Publications and source records attributed to Nguyen, V. D..

7 recordsLinked to original sources

bioRxiv2026

First Metagenome-Assembled Genomes from the Historic Morrow Plots Reveal Management-Associated Dominance of Archaeal Ammonia Oxidizers

Soil microbial communities underpin both soil health and agricultural productivity, yet genome-resolved resources from long-term field experiments remain limited. Here, we present a genome-resolved metagenomic dataset from the historic Morrow Plots long-term experiment in central USA, comprising 33 shotgun metagenomes collected across diverse crop rotation and fertilization treatments in year 149 of the experiment. Using a co-assembly, multi-binner workflow, we recovered 230 metagenome-assembled genomes (MAGs), including 44 archaeal and 186 bacterial genomes spanning multiple soil-associated phyla. Among these, 59 MAGs were linked to nitrogen-cycling functions, including ammonia- and nitrite-oxidizing lineages. The dataset also includes genome quality metrics, taxonomic classification, and treatment-resolved abundance patterns across different management regimes. Importantly, these nitrogen guild MAGs enable comparative analyses of nitrifier ecology, genome diversity, and functional variation linked to management in agricultural soils. Together, these resources establish a unique benchmark for studying how agricultural practices shape soil microbial communities at genome level, with associated long-term crop yield and soil fertility changes since the experiments inception in 1876.

microbiology↗

bioRxiv2026

HLA-DRB1*15:01 drives sex- and age-dependent microglial activation and neuroimmune signaling

IntroductionThe major histocompatibility complex class II (MHC-II) pathway is central to adaptive immunity and immune tolerance, and age-related erosion of these mechanisms is increasingly recognized as a driver of chronic neuroinflammation. The HLA-DRB1*15:01 allele--the strongest genetic risk factor for multiple sclerosis in Caucasians--has been implicated in shaping pathogenic CD4 T-cell responses and broader neuroimmune vulnerability, yet how this allele modulates age- and sex-dependent neuroimmune processes within the central nervous system (CNS) remains poorly defined. MethodsWe investigated the impact of HLA-DRB1*15:01 expression using a humanized mouse model (HLA mice) and wild-type (WT) controls. Male and female mice were analyzed at 6, 9, and 15 months of age, with endocrine stratification in females. Behavioral testing, flow cytometry, immunofluorescence, and multiplex cytokine analyses were used to assess cognitive performance, glial activation and oxidative stress, astrocyte-microglia IL-3/IL-3R signaling, endothelial activation, selective immune cell accumulation at CNS borders, tissue organization, and hippocampal cytokine profiles. ResultsHLA mice developed age- and sex-dependent cognitive impairment, most pronounced in aged females. HLA-DRB1*15:01 expression promoted progressive microglial activation, characterized by increased CD14 and CD68 expression, elevated mitochondrial oxidative stress, altered astrocyte phenotypes, and enhanced IL-3/IL-3R signaling. Hippocampal axonal and myelin organization was disrupted in aged HLA mice, and this disruption was spatially associated with increased microglial presence. At CNS interfaces, HLA mice exhibited selective immune remodeling, including increased accumulation of CD4 T cells and NK1.1CD3 natural killer T (NKT) cells, particularly in females, accompanied by endothelial activation, as evidenced by elevated ICAM-1 and E-selectin expression. Hippocampal cytokine profiling revealed selective, sex-biased alterations, including increased IL-12p70 and reduced IL-10 and IL-2, without broad induction of classical inflammatory cytokines. ConclusionTogether, these findings demonstrate that HLA-DRB1*15:01 drives a coordinated, age- and sex-dependent neuroinflammatory program linking behavioral dysfunction, glial activation and oxidative stress, selective immune cell recruitment, endothelial activation, tissue remodeling, and targeted cytokine imbalance. This integrated phenotype provides mechanistic insight into how this major MS risk allele confers vulnerability to chronic neuroinflammation during aging, with heightened impact in females.

neuroscience↗

bioRxiv2026

Excessive Ca2+-dependent ER-mitochondrial contact stabilization by EFHD1 drives liver injury

Metabolic-associated steatohepatitis (MASH) involves hepatocyte damage that cannot be explained solely by lipid accumulation. Here, to discover injury-specific pathways, we focused on a gene of uncertain function, EF-Hand Domain Family Member D1 (EFHD1), identified in human genome-wide association studies of liver injury but not liver fat. We show that EFHD1, a Ca2+-dependent actin crosslinker, stabilizes endoplasmic reticulum-mitochondria contact sites (ERMCS), detecting spatiotemporal coincidence of inter-organellar proximity and ER Ca2+ release. During MASH, EFHD1 upregulation drives pathological mitochondrial fragmentation via excessive contact persistence. This structural failure promotes mitochondrial double-stranded RNA escape and activation of a maladaptive antiviral PKR-dependent stress response, a causal relationship also supported by Mendelian randomization in humans. Consequently, inhibiting EFHD1 in human and mouse models blunts hepatocyte damage. These findings identify EFHD1 as a Ca2+-dependent ERMCS stabilizer, reveal a hepatocyte-intrinsic injury pathway, and suggest EFHD1 inhibition as a therapeutic strategy.

cell biology↗

bioRxiv2025

Complement biosynthesis in human brain: Insights from single-nucleus transcriptomics of hippocampus.

Complement is a key contributor to neuroinflammation, driving pathology in neurodegenerative diseases (NDDs); however, little is known about the source of complement in brain. Effective targeting of complement in NDDs requires understanding of its source; in particular, which brain cells express complement genes, how expression is regulated and how expression changes in disease. To address this knowledge gap, we identified and integrated single-nucleus RNA sequencing (snRNA-seq) datasets from 398,097 nuclei across 48 hippocampal samples from non-demented brains to create a comprehensive transcriptomic atlas of complement gene expression ("complementome") in healthy brain. Expression levels of genes encoding complement components, receptors, and regulators were analysed across different brain cell types and the impact of sex and age on complement gene expression tested. To test impact of disease, we generated a further atlas from datasets comprising 11 non-demented and 12 Alzheimers disease (AD) patient hippocampi to assess changes in complement gene expression in AD. All glial cells in the non-demented hippocampus expressed complement genes. C1Q A/B/C genes were exclusively expressed in microglia, while C3 was highly expressed in microglia and astrocytes. Notably, C3 expression defined a subset of pro-inflammatory microglia. Complement receptor encoding genes (C3AR1, C5AR2, ITGAM, ITGAX, ITGB2, VSIG4) were predominantly expressed in microglia, while neurons expressed a set of brain-specific putative receptors (NPTX 1/2, NPTXR, NRP1). Endothelial cells abundantly expressed key regulators (CD46, CD55, CD59, CFH), while neurons and OPCs expressed a set of putative regulators (CSMD 1/2/3, and SUSD4). Astrocytes abundantly expressed CLU. Cell type-specific gender differences included higher expression of C1Q A/B/C, C1R, C1S in female microglia and higher expression of ITGAM and ITGAX in male microglia. Generally higher complement gene expression was seen in older donors. Compared to controls, AD microglia showed higher expression of C1QB and C3, and AD astrocytes showed higher C1S and C3 expression. Expression of ITGAX was elevated in AD microglia compared to controls, while many AD cell types demonstrated reduced expression of brain-specific putative receptors. Defining the complementome in non-demented hippocampus provides a baseline for exploration of brain complement expression. Complement expression is upregulated in AD, likely contributing to neuroinflammation and highlighting its potential as a therapeutic target. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/652374v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@100fbc1org.highwire.dtl.DTLVardef@1905402org.highwire.dtl.DTLVardef@7b8573org.highwire.dtl.DTLVardef@176424a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

One-step generation of auxin-inducible degron cells with high-efficiency homozygous tagging

Auxin-inducible degron (AID) technology is powerful for chemogenetic control of proteolysis. However, generation of human cell lines to deplete endogenous proteins with AID remains challenging. Typically, homozygous degron-tagging efficiency is low and overexpression of an auxin receptor requires additional engineering steps. Here, we establish a one-step genome editing procedure with high-efficiency homozygous tagging and auxin receptor expression. We demonstrate its application in 5 human cell lines, including embryonic stem (ES) cells. The method allowed isolation of AID single-cell clones in 10 days for 11 target proteins with >80% average homozygous degron-tagging efficiency in A431 cells, and >50% efficiency for 5 targets in H9 ES cells. The tagged endogenous proteins were inducibly degraded in all cell lines, including ES cells and ES-cell derived neurons, with robust expected functional readouts. This method facilitates the application of AID for studying endogenous protein functions in human cells, especially in stem cells.

cell biology↗

bioRxiv2019

Target Of Rapamycin pathway in the white-rot fungus Phanerochaete chrysosporium

The Target Of Rapamycin (TOR) signaling pathway is known to regulate growth in response to nutrient availability and stress in eukaryotic cells. In the present study, we have investigated the TOR pathway in the white-rot fungus Phanerochaete chrysosporium. Inhibition of TOR activity by rapamycin affects conidia germination and hyphal growth highlighting the conserved mechanism of susceptibility to rapamycin. Interestingly, the secreted protein content is also affected by the rapamycin treatment. Finally, homologs of the components of TOR pathway can be identified in P. chrysosporium. Altogether, those results indicate that the TOR pathway of P. chrysosporium plays a central role in this fungus.

microbiology↗

bioRxiv2018

Phylotastic: improving access to tree-of-life knowledge with flexible, on-the-fly delivery of trees

(1) A comprehensive phylogeny of species, i.e., a tree of life, has potential uses in a variety of contexts in research and education. This potential is limited if accessing the tree of life requires special knowledge, complex software, or long periods of training.\n\n(2) The Phylotastic project aims to use web-services technologies to lower the barrier for accessing phylogenetic knowledge, making it as easy to get a phylogeny of species as it is to get online driving directions. In prior work, we designed an open system of web services to validate and manage species names, find phylogeny resources, extract subtrees matching a users species list, calibrate them, and mash them up with images and information from online resources.\n\n(3) Here we report a publicly accessible system for on-the-fly delivery of phylogenetic knowledge, developed with user feedback on what types of functionality are considered useful by researchers and educators. The system currently consists of a web portal that implements 3 types of workflows to obtain species phylogenies (scaled by geologic time and decorated with thumbnail images); 19 underlying web services accessible via a common registry; and toolbox code in R and Python so that others can create applications that leverage these services. These resources cover most of the use-cases identified in our analysis of user needs.\n\n(4) The Phylotastic system, accessible via http://www.phylotastic.org, provides a unique resource to access the current state of phylogenetic knowledge, useful for a variety of cases in which a tree extracted quickly from online resources (as distinct from a tree custom-made from character data) is sufficient, as it is for many casual uses of trees identified here.

bioinformatics↗