Synthesis of Indomorphan Pseudo Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3

Bioactive compound design based on natural product (NP) structure may be limited due to partial coverage of NP‐like chemical space and biological target space. These limitations can be overcome by combining NP‐centered strategies with fragment‐based compound design through combination of NP‐derived fragments to structurally unprecedented “pseudo natural products” (pseudo‐NPs). We describe the design, synthesis and biological evaluation of a collection of indomorphan pseudo‐NPs that combine biosynthetically unrelated indole‐ and morphan‐alkaloid fragments. Biological investigation in a cell‐based screen for modulators of glucose uptake identified the indomorphane derivative Glupin as potent inhibitor of glucose uptake. Glupin selectively targets and upregulates both, glucose transporters GLUT‐1 and GLUT‐3. Glupin suppresses glycolysis, reduces the levels of glucose‐derived metabolites and attenuates the growth of various cancer cell lines. Our findings underscore the importance of dual GLUT‐1 and GLUT‐3 inhibition to efficiently suppress tumor cell growth and the cellular rescue mechanism, which counteracts glucose scarcity

The coral core microbiome identifies rare bacterial taxa as ubiquitous endosymbionts

© 2015 International Society for Microbial Ecology All rights reserved. Despite being one of the simplest metazoans, corals harbor some of the most highly diverse and abundant microbial communities. Differentiating core, symbiotic bacteria from this diverse hostassociated consortium is essential for characterizing the functional contributions of bacteria but has not been possible yet. Here we characterize the coral core microbiome and demonstrate clear phylogenetic and functional divisions between the micro-scale, niche habitats within the coral host. In doing so, we discover seven distinct bacterial phylotypes that are universal to the core microbiome of coral species, separated by thousands of kilometres of oceans. The two most abundant phylotypes are co-localized specifically with the corals' endosymbiotic algae and symbiont-containing host cells. These bacterial symbioses likely facilitate the success of the dinoflagellate endosymbiosis with corals in diverse environmental regimes

Plant growth-promoting actinobacteria: a new strategy for enhancing sustainable production and protection of grain legumes

Grain legumes are a cost-effective alternative for the animal protein in improving the diets of the poor in South-East Asia and Africa. Legumes, through symbiotic nitrogen fixation, meet a major part of their own N demand and partially benefit the following crops of the system by enriching soil. In realization of this sustainability advantage and to promote pulse production, United Nations had declared 2016 as the “International Year of pulses”. Grain legumes are frequently subjected to both abiotic and biotic stresses resulting in severe yield losses. Global yields of legumes have been stagnant for the past five decades in spite of adopting various conventional and molecular breeding approaches. Furthermore, the increasing costs and negative effects of pesticides and fertilizers for crop production necessitate the use of biological options of crop production and protection. The use of plant growth-promoting (PGP) bacteria for improving soil and plant health has become one of the attractive strategies for developing sustainable agricultural systems due to their eco-friendliness, low production cost and minimizing consumption of non-renewable resources. This review emphasizes on how the PGP actinobacteria and their metabolites can be used effectively in enhancing the yield and controlling the pests and pathogens of grain legumes

Nitrogen partitioning in orchard-grown Macadamia integrifolia

Nut yield is highly variable in commercial macadamia production, and to ensure that nitrogen (N) Supply does not limit yield, high rates of N fertilizer are generally applied. To elucidate N source and sink relations in mature Macadamia integrifolia Maiden et Betche trees, we traced (15)N label after injection into individual branches and, after soil application, analysed xylem sap and examined the effects of hedging on tree N relations. Xylem sap N and sugar composition and concentration changed in relation to phenology and tree management. Canopy position did not affect xylem sap N concentration but sampling date had a significant effect. Hedging in spring was associated with a rapid and dramatic reduction of the concentration of xylem sap N until the following autumn, but unhedged trees were not available to unequivocally assess the significance of the results. Following (15)N-branch injection in winter, most (15)N label was incorporated into flushing leaves and into bark. After (15)N injection in spring, flushing leaves and flowers were most strongly (15)N-labelled. In late spring, (15)N label was equally incorporated by developing nuts that were retained or later abscised. Soil (15)N application in summer resulted in (15)N-labelling of outer and mid-canopy leaves. In the following spring, (15)N label was translocated to flushing leaves, flowers and developing nuts. The results indicate that outer and mid-canopy leaves are the main N sink for soil-derived N during the vegetative phase and a N Source for developing tissues during the reproductive phase. Our study provides evidence that N supply to developing nuts is not a primary cause for nut abscission, supporting the notion that high N fertilizer application rates do not improve nut retention. We propose that current orchard design and hedging practices should be reviewed in context of the role of outer canopy leaves as a source of N for reproductive tissues