Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies

Social contact with fungus-exposed ants leads to pathogen transfer to healthy nest-mates, causing low-level infections. These micro-infections promote pathogen-specific immune gene expression and protective immunization of nest-mates

Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Abstract The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two hypoallergenic rBet v 1 fragments were applied epicutaneously by atopy patch testing (APT) to 15 birch pollen (bp) allergic patients suffering from atopic dermatitis, 5 bp-allergic patients suffering from rhinoconjunctivitis only, 5 patients with respiratory allergy without bp allergy and 5 non-allergic individuals. Epicutaneous administration of rBet v 1 and rBet v 1 fragments led to strong and significant increases of allergen-specific T cell proliferation (CLA+ and CCR4+T cell responses) only in bp-allergic patients with a positive APT reaction. There were no relevant changes of Bet v 1-specific IgE and IgG responses. No changes were noted in allergic subjects without bp allergy and in non-allergic subjects. Epicutaneous allergen application boosts specific T cell but not antibody responses mainly in allergic, APT-positive patients suggesting IgE-facilitated allergen presentation as mechanism for its effects on systemic allergen-specific immune responses

The minimum amount of "matrix " needed for matrix-assisted pulsed laser deposition of biomolecules

The ability of matrix-assisted pulsed laser evaporation (MAPLE) technique to transfer and deposit high-quality thin organic, bioorganic, and composite films with minimum chemical modification of the target material has been utilized in numerous applications. One of the outstanding problems in MAPLE film deposition, however, is the presence of residual solvent (matrix) codeposited with the polymer material and adversely affecting the quality of the deposited films. In this work, we investigate the possibility of alleviating this problem by reducing the amount of matrix in the target. A series of coarse-grained molecular dynamics simulations are performed for a model lysozyme–water system, where the water serves the role of volatile “matrix” that drives the ejection of the biomolecules. The simulations reveal a remarkable ability of a small (5–10 wt %) amount of matrix to cause the ejection of intact bioorganic molecules. The results obtained for different laser fluences and water concentrations are used to establish a “processing map” of the regimes of molecular ejection in matrix-assisted pulsed laser deposition. The computational predictions are supported by the experimental observation of the ejection of intact lysozyme molecules from pressed lysozyme targets containing small amounts of residual water. The results of this study suggest a new approach for deposition of thin films of bioorganic molecules with minimum chemical modification of the molecular structure and minimum involvement of solvent into the deposition process

Chromopynones are pseudo natural product glucose uptake inhibitors targeting glucose transporters GLUT-1 and -3

The principles guiding the design and synthesis of bioactive compounds based on natural product (NP) structure, such as biology-oriented synthesis (BIOS), are limited by their partial coverage of the NP-like chemical space of existing NPs and retainment of bioactivity in the corresponding compound collections. Here we propose and validate a concept to overcome these limitations by de novo combination of NP-derived fragments to structurally unprecedented ‘pseudo natural products’. Pseudo NPs inherit characteristic elements of NP structure yet enable the efficient exploration of areas of chemical space not covered by NP-derived chemotypes, and may possess novel bioactivities. We provide a proof of principle by designing, synthesizing and investigating the biological properties of chromopynone pseudo NPs that combine biosynthetically unrelated chromane- and tetrahydropyrimidinone NP fragments. We show that chromopynones define a glucose uptake inhibitor chemotype that selectively targets glucose transporters GLUT-1 and -3, inhibits cancer cell growth and promises to inspire new drug discovery programmes aimed at tumour metabolism