Organic fishfarming requires robust fish

Da medicinbehandling af økologisk ørred er uønsket og kun er tilladt i stærkt begrænset omfang, er ynglens robusthed overfor bl.a. den alvorligste yngelsygdom i dansk ørredopdræt, YDS (”yngeldødeligheds-syndrom”), særdeles vigtig. Ynglens robusthed måles i forhold til ynglens swim-up adfærd (first feeding) og performance under opvæksten. Indholdet af specifikke essentielle Ω-3 fedtsyrer i foderet til ynglen er særlig vigtig for fiskens vækst, sundhed og velfærd, herunder robusthed overfor stress. Dette undersøges ved stress tests samt challenge tests over for YDS

An Integrated Metabolomic and Genomic Mining Workflow to Uncover the Biosynthetic Potential of Bacteria

Microorganisms are a rich source of bioactives; however, chemical identification is a major bottleneck. Strategies that can prioritize the most prolific microbial strains and novel compounds are of great interest. Here, we present an integrated approach to evaluate the biosynthetic richness in bacteria and mine the associated chemical diversity. Thirteen strains closely related to Pseudoalteromonas luteoviolacea isolated from all over the Earth were analyzed using an untargeted metabolomics strategy, and metabolomic profiles were correlated with whole-genome sequences of the strains. We found considerable diversity: only 2% of the chemical features and 7% of the biosynthetic genes were common to all strains, while 30% of all features and 24% of the genes were unique to single strains. The list of chemical features was reduced to 50 discriminating features using a genetic algorithm and support vector machines. Features were dereplicated by tandem mass spectrometry (MS/MS) networking to identify molecular families of the same biosynthetic origin, and the associated pathways were probed using comparative genomics. Most of the discriminating features were related to antibacterial compounds, including the thiomarinols that were reported from P. luteoviolacea here for the first time. By comparative genomics, we identified the biosynthetic cluster responsible for the production of the antibiotic indolmycin, which could not be predicted with standard methods. In conclusion, we present an efficient, integrative strategy for elucidating the chemical richness of a given set of bacteria and link the chemistry to biosynthetic genes. IMPORTANCE We here combine chemical analysis and genomics to probe for new bioactive secondary metabolites based on their pattern of distribution within bacterial species. We demonstrate the usefulness of this combined approach in a group of marine Gram-negative bacteria closely related to Pseudoalteromonas luteoviolacea, which is a species known to produce a broad spectrum of chemicals. The approach allowed us to identify new antibiotics and their associated biosynthetic pathways. Combining chemical analysis and genetics is an efficient “mining” workflow for identifying diverse pharmaceutical candidates in a broad range of microorganisms and therefore of great use in bioprospecting

A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency

The established causal genes in Alzheimer’s disease (AD), APP, PSEN1, and PSEN2, are functionally characterized using biomarkers, capturing an in vivo profile reflecting the disease’s initial preclinical phase. Mutations in SORL1, encoding the endosome recycling receptor SORLA, are found in 2%–3% of individuals with early-onset AD, and SORL1 haploinsufficiency appears to be causal for AD. To test whether SORL1 can function as an AD causal gene, we use CRISPR-Cas9-based gene editing to develop a model of SORL1 haploinsufficiency in Göttingen minipigs, taking advantage of porcine models for biomarker investigations. SORL1 haploinsufficiency in young adult minipigs is found to phenocopy the preclinical in vivo profile of AD observed with APP, PSEN1, and PSEN2, resulting in elevated levels of β-amyloid (Aβ) and tau preceding amyloid plaque formation and neurodegeneration, as observed in humans. Our study provides functional support for the theory that SORL1 haploinsufficiency leads to endosome cytopathology with biofluid hallmarks of autosomal dominant AD

The effect of dietary fatty acid content on rainbow trout fry robustness towards Flavobacterium psychrophilum

Among the most serious rainbow trout (Oncorhynchus mykiss) fry diseases in Danish aquaculture is Rainbow Trout Fry syndrome (RTFS), caused by the bacterium Flavobacterium psychrophilum. The robustness of the rainbow trout fry towards F. psychrophilum may be related to dietary lipid composition and the content of highly unsaturated omega-3 fatty acids (HUFAs). In the project RobustFish we tested the immune competence of 1g rainbow trout fry towards F. psychrophilum by experimental challenges with the bacterium, either intraperitoneal injection (triplicate aquaria with 30 fish per aquarium) or bath infection (duplicate aquaria with 60 fish per aquarium). Additionally, four experimental control aquaria for each challenge method. From first feeding and throughout the experimental period of 34 days for intraperitoneal injection and 55 days for bath infection the fry were fed three isoproteinous and isoenergetic diets specially made for this experiment containing vegetable rapeseed oil as the only lipid and supplemented by different levels of LC HUFAs (0.1, 1.1 or 2.5 % total EPA + DHA (as fed)). The levels of HUFA’s were adjusted with Incromega DHA 500TG (CRODA). One additional diet type was a commercial control from Aller-Aqua (ALLER FUTURA EX). All moribund fish seen during the two challenge experiments were euthanized and the spleen, kidney and brain examined for the presence of F. psychrophilum. Depending on diet type cumulated mortality by the end of the experiment ranged from (mean ± SD) 8 % (±4) to 43 % (±9) in the bath challenge and 70 % (±10) to 98 % (±2) in the intraperitoneal injection challenge. No mortality was observed in the experimental control. A strong correlation was found between final mortality in the bath and intraperitoneal injection challenges for the four types of diet. The effect of HUFAs on the robustness of rainbow trout fry towards F. psychrophilum will be discussed