Blue-fluorescence of NADPH as an indicator of marine primary production

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is the primary product of photosynthesisand can therefore serve as an indicator of biomass and photosynthetic activity. Pure NADPH whichis the reduced form of NADP shows an absorption maximum at 340 nm and a maximum of emissionat 460 nm. NADPH concentrations in terrestrial vegetation have already been studied since1957 in great detail with optical methods. However, its potential as a biomass parameter of oceanicphytoplankton which can be assessed in situ and remotely with fluorescence spectroscopy has notyet been investigated.In this paper, we report on laboratory investigations of the blue-fluorescence spectrum in algalsuspensions of Chlorella and Thalassiosira when excited with UV-A light. It is shown that cell densitiesof about 106 per litre as they are typically found under natural conditions are too low for precisedetection of NADPH fluorescence, while concentrated samples with 108-1010 cells per litre exhibitsignificant blue-fluorescence which can be related to NADPH. Inhibition of photosynthetic activityby addition of DCMU decreases the strength of blue-fluorescence remarkably. Since NADPHis an end product of photosynthesis, changes of PAR illumination levels should directly affect itsconcentration and hence the intensity of blue-fluorescence. However, no effect of illumination onblue-fluorescence could be observed in our study. Possible reasons of these observations are discussed,and perspectives for practical applications of the method used are proposed

Loss of tolerance to gut immunity protein; glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Abstract Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target

Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness