Biology subjects

Norberg, A.

Publications and source records attributed to Norberg, A..

3 recordsLinked to original sources

bioRxiv2026

Roles of Interstitial Albumin in the Subcutaneous Delivery of Therapeutic Peptides

Subcutaneous administration of biotherapeutics is increasingly favoured for better safety profile, improved stability, and patient compliance compared with intravenous administration. Despite these advantages, the roles of extracellular matrix (ECM) components and interstitial proteins, particularly albumin, in the mechanisms governing therapeutic pharmacokinetics and bioavailability remain poorly understood. We present a versatile and customizable hydrogel platform resembling native ECM in composition, charge density, and microstructure, enabling systematic investigation of transport mechanisms in the subcutaneous space. Using this platform, we studied peptides with different net charges and albumin affinities. Based on results from confocal microscopy combined with measurements of diffusivities by means of FRAP, we propose a role for albumin beyond that of transport vehicle for drugs. We show that reversible peptide-albumin binding can both increase bioavailability by removing peptides bound to the ECM biopolymers and modulate peptide diffusivity and distribution, as albumin was found to have an affinity for matrix glycosaminoglycans. For cationic peptides, albumin had a major influence on diffusivity and distribution in the matrix, with more pronounced effects over time in vitro. These findings, complemented by exploratory in vivo observations in a limited cohort, highlight realistic ECM structure and albumin inclusion as key considerations for predictive in vitro subcutaneous models.

biophysics↗

bioRxiv2019

Human pathogen co-occurrence in Ixodes ricinus ticks: effects of landscape topography, climatic factors and microbiota interactions

The factors shaping microbial communities within organisms are still poorly understood. Besides ecological factors and host characteristics, direct interactions among microbes may shape the occurrence of microbes and the structure of communities. In the past it has been difficult to disentangle if patterns of microbial co-occurrence are due to facilitation or competition effects, or shaped by shared ecological preferences (i.e., environmental filtering). Here we use a joint species distribution model to characterize the bacterial microbiota composition of an important human disease vector, the sheep tick Ixodes ricinus, along ecological gradients in the Swiss Alps, and to test for facilitation or competition effects among human pathogens and tick endosymbionts. We identify a number of ecological variables that significantly predicted the diversity of tick microbial community and the occurrence of specific tick endosymbionts and human pathogens. However, ecological associations were generally microbe-specific rather than universal. We also found evidence for significant microbe interactions, in particular widespread facilitation among pathogens, which promotes pathogen co-infection within ticks, as well as competition between the tick endosymbiont Spiroplasma and a number of human pathogens. These findings highlight that direct interactions among microbes can affect the vector competence of ticks and thereby tick-borne disease dynamics.

ecology↗

bioRxiv2016

Parasite-microbiota interactions potentially affect intestinal communities in wild mammals

Detecting interaction between species is notoriously difficult, and disentangling species associations in host-related gut communities is especially challenging. Nevertheless, due to contemporary methods, including metabarcoding and 16S sequencing, collecting observational data on community composition has become easier and much more common. We studied the previously collected data sets of intestinal microbiota and parasite compositions within longitudinally followed mouse lemurs by analysing the potential interactions with diversity metrics and novel joint species distribution modelling. Both methods showed consistent statistical association between certain parasite species and microbiotal composition. Both unicellular Eimeria sp. and cestode Hymenolepis diminuta had an effect on diversity of gut microbiota. These parasite species also had negative associations with several bacterial orders. In comparison, closely related species H. nana did not have an effect on diversity, and it had positive associations with several bacterial orders. Our results reveal potential interactions between some, but not all, intestinal parasites and gut microbiota. While environmental variables explained almost half of the total variation, of which almost half could be explained by traits of parasites and microbiota, there were no clear patterns regarding mouse lemur individual variables explaining variation in the occurrence patterns of parasite and microbiota significantly. Our results provide new hypothesis for interactions between and among parasites and microbiota to be tested further with experimental studies.

ecology↗