Bioassay-Guided Fractionation Leads to the Detection of Cholic Acid Generated by the Rare Thalassomonas sp.

Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas. The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environment

Negotiorum gestio En rettshistorisk avhandling om den romerske forretningsfører i det dansk-norske eneveldets og naturrettens tid

Masteravhandlingen er rettshistorisk. Den omhandler negotiorum gestio, såkalt uanmodet forretningsførsel, i Danmark-Norge på 1700-tallet. Avhandlingen har også et internasjonalt og komparativt utsyn ettersom den berører romersk rett i tillegg til naturrettstenkningen som preget Europa mellom 1600- og 1800-tallet

The use and misuse of methods for publication bias assessment and adjustment in meta-analyses of psychotherapeutic interventions: A systematic survey of the literature

Publication bias poses a threat to the validity of meta-analytic reviews, as it can lead to summary effect size estimates becoming inflated. Meta-analysts are advised to utilize multiple methods for detecting and controlling for publication bias. Our study aims to examine which and how many methods meta-analysts of psychotherapeutic interventions for depression, anxiety and PTSD utilize to identify and correct for publication bias, and to which extent they detect it. Additionally, we aim to provide some indication of the degree to which publication bias has (or has not) influenced meta-analytic estimates in this field, by reanalyzing meta-analyses for which study level data are available. 86 meta-analyses were included in our sample, and 37 meta-analyses also met the eligibility criteria for reanalysis. Findings demonstrate that 66 of 86 (76,7%) included meta-analyses utilized at least 1 publication bias method. 32 of 86 (37%) of the included meta-analyses utilized at least three publication bias methods. None of the included meta-analyses utilized a selection model approach. The funnel plot asymmetry tests varied from detecting publication bias on ~20% (Egger’s regression) to ~65% (trim-and-fill). The results from reanalyzes of study-level data indicates some inflation of effect size estimates, although the adjusted results generally do not considerably change the overall conclusions of these meta-analyses. Our overall findings indicate some degree of publication bias, that could go undetected because some meta-analysts do not sufficiently adhere to recommendations regarding publication bias methods

The bromotyrosine derivative Ianthelline isolated from the Arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling

International audienceThe inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro-and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1-10 mu g/mL) and barnacle larval settlement (IC50= 3.0 mu g/mL). Moderate effects are recorded on M. edulis (IC50= 45.2 mu g/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 mu g/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented

Antimicrobial Activity of Securamines From the Bryozoan Securiflustra securifrons

Natural products and their derivatives have served as powerful therapeutics against pathogenic microorganisms and are the mainstay of our currently available treatment options to combat infections. As part of our ongoing search for antimicrobial natural products from marine organisms, one fraction prepared from the Arctic marine bryozoan Securiflustra securifrons was found to be active against the human pathogenic bacterium Streptococcus agalactiae (gr. B). Chemical investigation of the fraction revealed that it contained several variants of the highly modified secondary metabolites known as securamines. The securamines are alkaloids sharing a common isoprene-histamine-tryptamine backbone. In this study, we describe the antimicrobial activities of securamine C, E, and H – J (4, 5, and 1-3) and the attempt to deconvolute the mode of action of 1

Qualitative and Quantitative Comparison of Liquid–Liquid Phase Extraction Using Ethyl Acetate and Liquid–Solid Phase Extraction Using Poly-Benzyl-Resin for Natural Products

A key step in the process of isolating microbial natural products is the preparation of an extract from a culture. This step determines which molecules will be available for detection in the subsequent chemical and biological analysis of a biodiscovery pipeline. In the present study we wanted to document potential differences in performance between liquid–liquid extraction using ethyl acetate and liquid–solid extraction using a poly‐benzyl‐resin. For the comparison of the two extraction protocols, we spiked a culture of Flavobacterium sp. with a diverse selection of natural products of microbial and plant origin to investigate whether the methods were comparable with respect to selectivity. We also investigated the efficiency of the two extraction methods quantita‐ tively, using water spiked with a selection of natural products, and studied the quantitative effect of different pH levels of the aqueous solutions on the extraction yields of the two methods. The same compounds were extracted by the two methods, but the solid‐phase extract contained more media components compared with the liquid‐phase extract. Quantitatively, the two extraction methods varied in their recovery rates. We conclude that practical aspects could be more important when selecting one of the extraction protocols, as their efficiencies in extracting specific compounds were quite similar

Recommendations for health monitoring of pig, cat, dog and gerbil breeding colonies: Report of the Scandinavian Federation for Laboratory Animal Science (Scand-LAS) Working Group of Animal Health

No abstract availabl

Lulworthinone, a New Dimeric Naphthopyrone From a Marine Fungus in the Family Lulworthiaceae With Antibacterial Activity Against Clinical Methicillin-Resistant Staphylococcus aureus Isolates

The emergence of drug-resistant bacteria is increasing rapidly in all parts of the world, and the need for new antibiotics is urgent. In our continuous search for new antimicrobial molecules from under-investigated Arctic marine microorganisms, a marine fungus belonging to the family Lulworthiaceae (Lulworthiales, Sordariomycetes, and Ascomycota) was studied. The fungus was isolated from driftwood, cultivated in liquid medium, and studied for its potential for producing antibacterial compounds. Through bioactivity-guided isolation, a novel sulfated biarylic naphtho-α-pyrone dimer was isolated, and its structure was elucidated by spectroscopic methods, including 1D and 2D NMR and HRMS. The compound, named lulworthinone (1), showed antibacterial activity against reference strains of Staphylococcus aureus and Streptococcus agalactiae, as well as several clinical MRSA isolates with MICs in the 1.56–6.25 μg/ml range. The compound also had antiproliferative activity against human melanoma, hepatocellular carcinoma, and non-malignant lung fibroblast cell lines, with IC50 values of 15.5, 27, and 32 μg/ml, respectively. Inhibition of bacterial biofilm formation was observed, but no eradication of established biofilm could be detected. No antifungal activity was observed against Candida albicans. During the isolation of 1, the compound was observed to convert into a structural isomer, 2, under acidic conditions. As 1 and 2 have high structural similarity, NMR data acquired for 2 were used to aid in the structure elucidation of 1. To the best of our knowledge, lulworthinone (1) represents the first new bioactive secondary metabolite isolated from the marine fungal order Lulworthiales