Search Results (7)

Cyanobacterial harmful algal blooms (cHABs) are increasing due to eutrophication and climate change, as is irrigation of crops with freshwater contaminated with cHAB toxins. A few studies, mostly in aquatic protists and plants, have investigated the effects of cHAB toxins or cell extracts on various aspects of photosynthesis, with variable effects reported (negative to neutral to positive). We examined the effects of cyanobacterial live cultures and cell extracts (Microcystis aeruginosa or Anabaena flos-aquae) and individual cHAB toxins (anatoxin-a, ANA; beta-methyl-amino-L-alanine, BMAA; lipopolysaccharide, LPS; microcystin-LR, MC-LR) on photosynthesis in intact plants and leaf pieces in corn (Zea mays) and lettuce (Lactuca sativa). In intact plants grown in soil or hydroponically, overall net photosynthesis (P_n), but not Photosystem-II (PSII) electron-transport yield (Φ_PSII), decreased when roots were exposed to cyanobacterial culture (whether with intact cells, cells removed, or cells lysed and removed) or individual toxins in solution (especially ANA, which also decreased rubisco activity); cyanobacterial culture also decreased leaf chlorophyll concentration. In contrast, Φ_PSII decreased in leaf tissue vacuum-infiltrated with cyanobacterial culture or the individual toxins, LPS and MC-LR, though only in illuminated (vs. dark-adapted) leaves, and none of the toxins caused significant decreases in in vitro photosynthesis in thylakoids. Principal component analysis indicated unique overall effects of cyanobacterial culture and each toxin on photosynthesis. Hence, while cHAB toxins consistently impacted plant photosynthesis at ecologically relevant concentrations, the effects varied depending on the toxins and the mode of exposure. Full article

Staphylococcus aureus causes a wide range of infections, and it is one of the leading pathogens responsible for deaths associated with antimicrobial resistance, the rapid spread of which among S. aureus urges the discovery of new antibiotics. The evaluation of in vivo efficacy of novel drug candidates is usually performed using animal models. Recently, zebrafish (Danio rerio) embryos have become increasingly attractive in early drug discovery. Herein, we established a zebrafish embryo model of S. aureus infection for evaluation of in vivo efficacy of novel potential antimicrobials. A local infection was induced by microinjecting mCherry-expressing S. aureus Newman followed by treatment with reference antibiotics via microinjection into different injection sites as well as via waterborne exposure to study the impact of the administration route on efficacy. We successfully used the developed model to evaluate the in vivo activity of the natural product sorangicin A, for which common mouse models were not successful due to fast degradation in plasma. In conclusion, we present a novel screening platform for assessing in vivo activity at the antibiotic discovery stage. Furthermore, this work provides consideration for the choice of an appropriate administration route based on the physicochemical properties of tested drugs. Full article

G protein-coupled receptors (GPCRs) transfer extracellular signals across cell membranes by activating intracellular heterotrimeric G proteins. Several studies suggested G proteins as novel drug targets for the treatment of complex diseases, e.g., asthma and cancer. Recently, we developed specific radiotracers, [³H]PSB-15900-FR and [³H]PSB-16254-YM, for the Gα_q family of G proteins by tritiation of the macrocyclic natural products FR900359 (FR) and YM-254890 (YM). In the present study, we utilized these potent radioligands to perform autoradiography studies in tissues of healthy mice, mouse models of disease, and human tissues. Specific binding was high, while non-specific binding was extraordinarily low, giving nearly identical results for both radioligands. High expression levels of Gα_q proteins were detected in healthy mouse organs showing the following rank order of potency: kidney > liver > brain > pancreas > lung > spleen, while expression in the heart was low. Organ sub-structures, e.g., of mouse brain and lung, were clearly distinguishable. Whereas an acute asthma model in mice did not result in altered Gα_q protein expressions as compared to control animals, a cutaneous melanoma model displayed significantly increased expression in comparison to healthy skin. These results suggest the future development of Gα_q-protein-binding radio-tracers as novel diagnostics. Full article

Zebrafish (ZF; Danio rerio) larvae have become a popular in vivo model in drug metabolism studies. Here, we investigated the metabolism of methyl 2-[1-(4-fluorobutyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate (4F-MDMB-BINACA) in ZF larvae after direct administration of the cannabinoid via microinjection, and we visualized the spatial distributions of the parent compound and its metabolites by mass spectrometry imaging (MSI). Furthermore, using genetically modified ZF larvae, the role of cannabinoid receptor type 1 (CB1) and type 2 (CB2) on drug metabolism was studied. Receptor-deficient ZF mutant larvae were created using morpholino oligonucleotides (MOs), and CB2-deficiency had a critical impact on liver development of ZF larva, leading to a significant reduction of liver size. A similar phenotype was observed when treating wild-type ZF larvae with 4F-MDMB-BINACA. Thus, we reasoned that the cannabinoid-induced impaired liver development might also influence its metabolic function. Studying the metabolism of two synthetic cannabinoids, 4F-MDMB-BINACA and methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB), revealed important insights into the in vivo metabolism of these compounds and the role of cannabinoid receptor binding. Full article

Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation, and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing, and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria. Full article

The most widely employed industrial process for producing alumina (Bayer process) involves the dissolution of available aluminium hydroxide minerals present in raw bauxite into high temperature sodium hydroxide solutions. On cooling of the solution, or liquor in the industrial vernacular, Al is precipitated from solution in the form of gibbsite (Al(OH)₃). In order to optimise the process, a detailed knowledge of factors influencing gibbsite solubility is required, a problem that is confounded by the presence of liquor impurities. In this paper, the use of the Group Method of Data Handling (GMDH) polynomial neural network for developing a gibbsite equilibrium solubility model for Bayer process liquors is discussed. The resulting predictive model appears to correctly incorporate the effects of liquor impurities and is found to offer a level of performance comparable to the most sophisticated phenomenological model presented to date. Full article