Biology subjects

Cornelius, J.

Publications and source records attributed to Cornelius, J..

3 recordsLinked to original sources

bioRxiv2026

Characterization of Resolved, Localized, and Progressing Infections at the Maternal-Fetal Interface in a Nonhuman Primate Model

Background: Inflammation and infection are responsible for the majority of early preterm births. Host innate immune responses at the maternal-fetal interface that contribute to sterile intra-amniotic inflammation (SIAI), bacterial clearance, or invasive infection remain poorly understood. Group B Streptococcus (Streptococcus agalactiae) is a leading cause of preterm birth, stillbirth, and invasive neonatal disease. Objective: To determine the host innate immune factors and transcriptional profiles that characterize the persistence versus resolution of a Group B Streptococcus infection at the maternal-fetal interface in a nonhuman primate (pigtail macaque, Macaca nemestrina) model. We hypothesized that a highly inflammatory profile, associated with interleukin-1 signaling, is linked to progression, whereas a mild or non-inflammatory signature is associated with infection resolution. Study Design: In a chronically catheterized pregnant pigtail macaque model, Group B Streptococcus was inoculated into the choriodecidual space. Infections were classified as progressing (invasive into the amniotic fluid), localized (bacteria persisting at the inoculation site), or resolved (minimal to no bacteria detected). Temporal and spatial RNA and protein profiles in the chorioamniotic membranes and decidua and in the myometrium were assessed by histopathology, multiplex protein assays, total RNA-sequencing, Nanostring nCounter, and spatial transcriptomics (digital spatial profiling). Differential gene expression was analyzed with limma using moderated t-tests and by gene set enrichment analysis. Results: A GBS infection at the maternal-fetal interface produced three infection outcomes: progressing infections that disseminated into the amniotic fluid (AF, N=5), low-titer localized infections remaining at the inoculation site (N=6), and resolved infections (N=5), compared with saline controls (N=3). Preterm labor occurred frequently regardless of infection outcome (40-80%). In resolved infections, SIAI occurred in the AF and lymphocytes infiltrated the myometrium. Total RNA-Seq of the chorioamniotic membranes demonstrated that 99 genes separated progressing from resolved infections, 98 of them were upregulated and dominated by IL-1 signaling and granulocyte recruitment (i.e., IL1B, CXCL8, TLR2, CLEC4A). Histone deacetylase 10 (HDAC10) was the only significantly downregulated gene in the progressing versus resolved contrast (p<0.05). An exploratory spatial transcriptomics experiment localized the progressing inflammatory response to the chorion. In the myometrium, zinc and RING finger 3 (ZNRF3) was significantly downregulated in localized versus control and resolved versus control and was also the only differentially expressed gene. Downregulated WNT signaling and upregulated lymphocyte-mediated immunity gene sets in the myometrium were a signature of resolved infections. Conclusion: A GBS infection at the maternal-fetal interface can result in a spectrum of progressing, localized and resolved outcomes. An early IL-1 and granulocyte response in the chorion layer of the chorioamniotic membranes marks bacterial dissemination, with loss of HDAC10 suggesting epigenetic regulation within the membranes with progressing infections. In the myometrium, ZNRF3 and downregulation of WNT signaling persisted even after infection resolution, reflecting an infectious exposure. Unexpectedly, resolved infections were associated with SIAI and a myometrial inflammatory response, offering a possible explanation for preterm labor associated with SIAI.

systems biology↗

bioRxiv2025

From literature to biodiversity data: mining arthropod organismal and ecological traits with machine learning

The fields of taxonomy and biodiversity research have witnessed an exponential growth in published literature. This vast corpus of articles holds information on the diverse biological traits of organisms and their ecologies. However, access to and extraction of relevant data from this extensive resource remain challenging. Advances in text and data mining (TDM) and Natural Language Processing (NLP) techniques offer new opportunities for liberating such information from the literature. Testing and using such approaches to annotate articles in machine actionable formats is therefore necessary to enable the exploitation of existing knowledge in new biology, ecology, and evolution research. Here we explore the potential of these methods to annotate and extract organismal and ecological trait data for the most diverse animal group on Earth, the arthropods. The article processing workflow uses manually curated trait dictionaries with trained NLP models to perform labelling of entities and relationships of thousands of articles. A subset of manually annotated documents facilitated the formal evaluation of the performance of the workflow in terms of entity recognition and normalisation, and relationship extraction, highlighting several important technical challenges. The results are made available to the scientific community through an interactive web tool and queryable resource, the ArTraDB Arthropod Trait Database. These methodological explorations provide a framework that could be extended beyond the arthropods, where TDM and NLP approaches applied to the taxonomy and biodiversity literature will greatly facilitate data synthesis studies and literature reviews, the identification of knowledge gaps and biases, as well as the data-informed investigation of ecological and evolutionary trends and patterns.

bioinformatics↗

bioRxiv2020

Intraflagellar transport-A deficiency ameliorates ADPKD renal cystogenesis in a renal tubular- and maturation-dependent manner

Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multi-protein complexes. Deletion of different IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult Autosomal Dominant (AD) PKD mouse models, while deletion of an IFT-A adaptor, Tulp3, attenuates PKD severity in adult mice only. These studies indicate that dysfunction of specific cilia components has potential therapeutic value. To broaden our understanding of cilia dysfunction and its therapeutic potential, here we investigate the impact of global deletion of an IFT-A gene, Thm1, in juvenile and adult ADPKD mouse models. Both juvenile and adult models exhibited increased kidney weight:body weight (KW/BW) ratios, renal cysts, inflammation, lengthened renal cilia, and increased levels of the nutrient sensor, O-linked {beta}-N-acetylglucosamine (O-GlcNAc). Thm1 deletion in juvenile ADPKD mice reduced KW/BW ratios and cortical collecting duct cystogenesis, but increased proximal tubular and glomerular dilations and did not reduce inflammation, cilia lengths, and O-GlcNAc signaling. In contrast, Thm1 deletion in adult ADPKD mice markedly attenuated renal cystogenesis, inflammation, cilia lengths, and O-GlcNAc. Thus, unlike IFT-B genes, the role of Thm1 deletion in ADPKD mouse models is development-specific. Unlike an IFT-A adaptor gene, deleting Thm1 in juvenile ADPKD mice is partially ameliorative. Our studies suggest that different microenvironmental factors found in distinct nephron segments and between developing and mature kidneys modify ciliary homeostasis and ADPKD pathobiology. Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a novel feature and critical regulator of certain key ADPKD pathological processes.

genetics↗