In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker

Purpose: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity. Methods: S100A9−/−cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9−/− mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated. Results: In S100A9−/−mice contrast-to-noise-ratios were significantly reduced for wt and S100A9−/−tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group. Conclusion: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity

Final results of the 12-POF-RX project

Fully integrated optical receivers are essential components for low cost, low power consuming and reliable POF data transmission links. In a joint Bavarian project a new design with optimized pin-photo diodes and integrated amplifiers was developed. Main applications are data transmission systems with bit rated between 1 and 5 Gbit/s

Turritelline mass accumulations from the Lower Miocene of southern Germany: implications for tidal currents and nutrient transport within the North Alpine Foreland Basin

The mass occurrence of turritelline gastropod shells from the Lower Miocene of southern Germany allows for detailed studies of their palaeoecology, transport mechanisms, preservation potentials and the reconstruction of nutrient regimes. Changes in the fabric of the gastropod-dominated beds are used to reconstruct a generally deepening environment corresponding to the Lower Miocene transgression within the Upper Molasse Sea of the North Alpine Foreland Basin. The sedimentary succession ranges from chaotically arranged, densely packed and near-shore transported; wave-influenced deposits showing bimodal shell orientations; more widely dispersed shells showing a uni-directional orientation; and dispersed shells showing diverse orientations. The shells often show damage to the apex and aperture though it is not clear whether this is due to predation events, pagurisation or abrasion due to transport. An outstanding feature is the replacement of aragonite shells by calcite leading to internal vugs as well as modulating the outer shell surface morphology. The high density of turritelline gastropods indicates a nutrient-rich palaeoenvironment at the northern edge of the Molasse Sea

In situ/Subcellular localization of arabinogalactan protein expression by fluorescent in situ hybridization, FISH

31 p. Methods Mol Biol 2149:403-427The arabinogalactan proteins are highly glycosylated and ubiquitous in plants. They are involved in several aspects of plant development and reproduction; however, the mechanics behind their function remains for the most part unclear, as the carbohydrate moiety, covering the most part of the protein core, is poorly characterized at the individual protein level. Traditional immunolocalization using antibodies that recognize the glycosidic moiety of the protein cannot be used to elucidate individual proteins' distribution, function, or interactors. Indirect approaches are typically used to study these proteins, relying on reverse genetic analysis of null mutants or using a reporter fusion system. In the method presented here, we propose the use of RNA probes to assist in the localization of individual AGPs expression/mRNAs in tissues of Arabidopsis by fluorescent in situ hybridization, FISH. An extensive description of all aspects of this technique is provided, from RNA probe synthesis to the hybridization, trying to overcome the lack of specific antibodies for the protein core of AGPs.This work was financed by FEDER through the COMPETE program, and by Portuguese National funds through FCT, Fundação para a Ciência eTecnologia (Project PTDC/AGR-GPL/115358/2009 and FCT - 02-SAICT-2017 – POCI-01-0145-FEDER-027839) and PhD grant SFRH/BD/111781/2015), and received support from Spanish–Portuguese Joint Project Nº E 30/12. EU project 690946 ‘SexSeed’ (Sexual Plant Reproduction – Seed Formation) funded by H2020-MSCA-RISE-2015.Peer reviewe