The present study compared genetically modified (GM) crops with crops from different farming practices using high-resolution tandem mass spectrometry (HR-MS) and proteomics bioinformatics tools. In... Show moreThe present study compared genetically modified (GM) crops with crops from different farming practices using high-resolution tandem mass spectrometry (HR-MS) and proteomics bioinformatics tools. In a previously pub-lished study, a number of significant differences regarding nutritional and elemental composition between a selection of GM, non-GM conventionally farmed, and organic soybeans have been found. In the present study, the proteome-level equivalence of the same samples was assessed using HR-MS. Direct comparison of tandem mass spectra and bottom-up proteomics bioinformatics indicated that proteomes of all samples investigated were very similar overall, with only a few distinct protein expression clusters obtained for GM and organic samples. Standard bottom-up proteome analyses identified 1025 soy proteins; of these 39 were found to be differentially expressed (p < 0.01) between GM, non-GM conventionally farmed, and organically farmed soybeans. Subsequent bioinformatics analyses of these proteins highlighted several potentially affected biochemical pathways that could contribute to the compositional differences reported earlier. In addition, protein markers separating conventionally, and organically farmed soybean seeds were found and peptide markers for the detection of GM soy in food and feed samples are described. Taken together, the data presented here shows that HR-MS based proteomics approaches can be used for the detection of transgenic events in food and feed grade soy, the dif-ferentiation of organically and conventionally farmed plants, and provide mechanistic explanations of effects observed on the phenotypic level of GM plants. HR-MS and proteomic bioinformatics thus should be considered key tools when developing molecular panel approaches for detection and safety assessments of novel crop va-rieties destined for use in feed and food. Show less
The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non... Show moreThe acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape. Show less
Klein, M.; Bruhl, T.J.; Staudt, V.; Reuter, S.; Grebe, N.; Gerlitzki, B.; ... ; Bopp, T. 2015
