Biology subjects

Knudsen, C.

Publications and source records attributed to Knudsen, C..

4 recordsLinked to original sources

bioRxiv2025

MilkOligoCorpus: a semantically annotated resource for knowledge extraction on mammalian milk oligosaccharides

Milk oligosaccharides are bioactive components that regulate the composition of the neonatal microbiota and exert immunomodulatory functions. Their beneficial effects depend on their structure. Numerous studies have shown intra- and inter-species variation in the structural composition and concentration of these compounds in mammalian milk, yet the biological significance of such variation remains poorly understood. Automated natural language processing methods are promising tools for extracting and gathering structured data from unstructured texts to get insight into the biological significance of milk oligosaccharide variation across mammals. These methods require training and evaluation on manually annotated text corpora. While annotated corpora exist for chemical substances, none are specifically designed for training natural language processing models to extract information on milk oligosaccharides. To this end, we propose MilkOligoCorpus, a new gold standard for milk oligosaccharide composition in mammalian species. MilkOligoCorpus annotation scheme is a rich entity/relation model designed to describe the diversity pattern of milk oligosaccharides according to female factor variability and to help better understand the structure-related function of milk oligosaccharides. MilkOligoCorpus consists of 30 PubMed texts fully annotated with entities related to individuals, samples, oligosaccharides and oligosaccharide quantification linked by binary and n-ary relationships. To address data interoperability across disparate publications and databases, four terminological resources were also developed to assign unique identifiers to the entities, supported by external ontologies. This paper presents the creation of the MilkOligoCorpus and its associated schema, along with the development of annotation guidelines and terminological resources. We also present experimental results obtained by baseline information extraction models on the corpus.

bioinformatics↗

bioRxiv2024

A single-cell atlas of transcriptome changes in the intestinal epithelium at the suckling-to-weaning transition

The suckling-to-weaning dietary transition is a key step in mammalian intestinal development. However, the relative contributions of genetically wired and nutritional factors in this maturation process remain to be elucidated. Moreover, the cellular diversity of the intestinal epithelium has been overlooked in this context. The aim of our study was to identify the transcriptome changes induced in each cell type of the intestinal epithelium at the onset of solid food ingestion. We compared the single-cell transcriptome of epithelial cells isolated from the caecum of age-matched littermate suckling rabbits ingesting or not solid food. Our dataset provides the first single-cell atlas of the rabbit intestinal epithelium and highlights the interest of the rabbit as a model for studying BEST4+ epithelial cells, which are absent in mice. Solid food ingestion induced extensive transcriptome changes in each epithelial cell type, with the most pronounced changes noted in absorptive and BEST4+ cells. Some of the effects of solid food introduction were common to most epithelial cell types, such as the upregulation of ALDH1A1, which encodes for a vitamin A processing enzyme. Solid food ingestion remodeled epithelial defenses systems, as observed by the increased expression of interferon-stimulated genes in mature absorptive and BEST4+ cells. Solid food also upregulated the gene expression of the immunoglobulin transporter PIGR, specifically in cells located at the base of epithelial crypts and in goblet cells. In addition, solid food triggered epithelial differentiation, which was associated with modification of the expression of genes involved in handling of amino acids, lipids and bile acids, as well as changes in hormone expression by enteroendocrine cells. These cell type-specific transcriptome modifications induced by solid food ingestion coincided with changes in microbiota composition and metabolic activity, which may contribute to epithelial maturation. Overall, our work provides a single-cell atlas of the transcriptome changes induced in the intestinal epithelium at the suckling-to-weaning transition.

physiology↗

bioRxiv2022

Prototyping of a lateral flow assay based on monoclonal antibodies for detection of Bothrops venoms

BackgroundBrazil is home to a multitude of venomous snakes, perhaps the most medically relevant of which belong to the Bothrops genus. Bothrops spp. are responsible for roughly 70% of all snakebites in Brazil, and envenomings caused by their bites can be treated with three types of antivenom: bothropic antivenom, bothro-lachetic antivenom, and bothro-crotalic antivenom. The choice in antivenom that is administered depends not only on its availability and how certain the treating physician is that the patient was bitten by a bothropic snake. The diagnosis of a bothropic envenoming can be made based on expert identification of a photo of the snake or based on a syndromic approach wherein the clinician examines the patient for characteristic manifestations of envenoming. This approach can be very effective but requires staff that has been trained in clinical snakebite management, which, unfortunately, far from all relevant staff has. ResultsIn this paper, we describe a prototype of the first lateral flow assay (LFA) capable of detecting venoms from Brazilian Bothrops spp. The monoclonal antibodies for the assay were generated using hybridoma technology and screened in sandwich enzyme-linked immunosorbent assays (ELISAs) to identify Bothrops spp. specific antibody sandwich pairs. The sandwich pairs were used to develop a prototype LFA that was able to detect venom from several different Bothrops spp. The limit of detection (LoD) of the prototype was evaluated using Brazilian B. atrox whole venom and was determined to be 8.0 ng/mL in spiked serum samples and 9.5 ng/mL in spiked urine samples, when using a portable reader, and < 25 ng/mL in spiked buffer when reading by eye. SignificanceThe work presented here serves as a proof of concept of a genus-specific venom detection kit, which could support physicians in diagnosing Bothrops envenomings. Although further optimization and testing is needed before the LFA can find clinical use, such a device could aid in decentralizing antivenoms in the Brazilian Amazon and help ensure optimal snakebite management for even more victims of this highly neglected disease.

immunology↗

bioRxiv2020

Across kingdom biased CYP-mediated metabolism via small-molecule ligands docking on P450 oxidoreductase

Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natural product biosynthesis in plants. The mechanisms underlying POR-mediated CYP metabolism remain poorly understood and to date no ligand binding has been described to regulate the specificity of POR. Here, using a combination of computational modeling and functional assays, we identified ligands that dock on POR and bias its specificity towards CYP redox partners. Single molecule FRET studies revealed ligand docking to alter POR conformational sampling, which resulted in biased activation of metabolic cascades in whole cell assays. We propose the model of biased metabolism, a mechanism akin to biased signaling of GPCRs, where ligand docking on POR stabilizes different conformational states that are linked to distinct metabolic outcomes. Biased metabolism may allow designing pathway-specific therapeutics or personalized food suppressing undesired, disease related, metabolic pathways.

biophysics↗