Biology subjects

Backlund, A.

Publications and source records attributed to Backlund, A..

4 recordsLinked to original sources

bioRxiv2026

The Metabolome of Drosophila Reveals Exercise-Induced Stress and Anti-Inflammatory Response

Exercise is a known remedy for metabolic disorders, including obesity and type II diabetes. In humans and some model organisms, exercise is classified into different types and intensities based on the mode of exercise and the devices used. Since Drosophila has emerged as a model for exercise research, several devices have been developed for exercise training. These devices vary in mechanisms of operation; for example, the Power Tower (PT) uses a repeated drop-and-hit mechanism, and the TreadWheel (TW) uses end-over-end rotation. This variation in mechanisms that trigger the negative geotaxis of flies could impact exercise outcomes, and it remains unclear how this variation drives the response of flies to exercise training. Stress is a known response to exercise in humans and mice. Stress in Drosophila can be induced by various conditions, including heat, cold, chemical exposure, and other environmental stressors, but there is little information on exercise-induced stress. It is also unclear whether different devices elicit distinct stress responses or whether the exercise-induced stress response is similar to other stress responses (e.g., thermal, chemical). To explore the effects of device, sex, and genotype on multiple metabolic pathways, we used an untargeted metabolomics approach to further elucidate the molecular mechanisms of exercise. As no studies have directly examined the exercise metabolome of Drosophila, this study is the first to explore the metabolome of flies post-exercise. Our results revealed that exercising on different devices elicits varying responses and reshapes the metabolome of flies. We also identified specific small compounds that may be linked to stress and inflammatory response more in the PT-exercised flies than in the TW-exercised flies. Overall, the exercise device effect interacted with sex effect and genotype, such that male and female flies have different metabolite compositions post-exercise on TW and PT.

Molecular Biology↗

bioRxiv2022

Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression

Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target Fibroblast Growth Factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal models of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.

molecular biology↗

bioRxiv2020

Survival and growth of saprotrophic and mycorrhizal fungi in recalcitrant amine, amide and ammonium containing media

The elimination of hazardous compounds in chemical wastes can be a complex and technically demanding task. In the search for environmental-friendly technologies, fungal mediated remediation and removal procedures are of concern. In this study, we investigated whether there are fungal species that can survive and grow on solely amine-containing compounds. One compound containing a primary amine group; 2-diethylaminoethanol, one compound with a primary amide group; 2,6-dichlorobenzamide (BAM), and a third compound containing a quaternary ammonium group; N3-trimethyl(2-oxiranyl)methanaminium chloride, were selected. The choice of these compounds was motivated by their excessive use in large scale manufacturing of protein separation media (2-diethylaminoethanol and the quaternary amine). 2,6-dichlorobenzamide, the degradation product of the herbicide 2,6-dichlorobenzonitrile (dichlobenil), was chosen since it is an extremely recalcitrant compound. Utilising part of the large fungal diversity in Northern European forests, a screening study using 48 fungal isolates from 42 fungal species, including saprotrophic and mycorrhizal fungi, was performed to test for growth responses to the chosen compounds. The ericoid mycorrhizal fungus Rhizoscyphus ericae showed the best overall growth on 2-diethylaminoethanol and BAM in the 1-20 gL-1 concentration range. A 3500% and 450% increase in biomass, respectively, was observed. For N3-trimethyl(2-oxiranyl)methanaminium chloride, the peak growth occurred at 1 gL-1. In a second experiment, including three of the most promising species (Laccaria laccata, Hygrophorus camarophyllus and Rhizoscyphus ericae) from the screening experiment, a simulated process water containing 1.9% (w/v) 2-diethylaminoethanol and 0.8% (w/v) N3-trimethyl(2-oxiranyl)methanaminium chloride was used. Laccaria laccata showed the best biomass growth increase (380%) relative to a growth control, while the growth increase for Rhizoscyphus ericae and H. camarophyllus were 292% and 136% respectively, showing that also mycorrhizal fungal species can use amine- and amide-containing substrates as nutrients. These results show the potential of certain fungal species to be used in alternative green wastewater treatment procedures.

microbiology↗

bioRxiv2020

Engineering of extracellular vesicles for display of protein biotherapeutics

Extracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While a range of engineering strategies have been developed to functionalize the EV surface, current approaches fail to address the limitations associated with endogenous surface display, pertaining to the heterogeneous display of commonly used EV-loading moieties among different EV subpopulations. Here we present a novel engineering platform to display multiple protein therapeutics simultaneously on the EV surface. As proof-of-concept, we screened multiple endogenous display strategies for decorating the EV surface with cytokine binding domains derived from tumor necrosis factor receptor 1 (TNFR1) and interleukin 6 signal transducer (IL6ST), which can act as decoys for the pro-inflammatory cytokines TNF and IL6, respectively. Combining synthetic biology and systematic screening of loading moieties, resulted in a three-component system which increased the display and decoy activity of TNFR1 and IL6ST, respectively. Further, this system allowed for combinatorial functionalization of two different receptors on the same EV surface. These cytokine decoy EVs significantly ameliorated disease phenotypes in three different inflammatory mouse models for systemic inflammation, neuroinflammation, and intestinal inflammation. Importantly, significantly improved in vitro and in vivo efficacy of these engineered EVs was observed when compared directly to clinically approved biologics targeting the IL6 and TNF pathways.

bioengineering↗