Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy.

Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2. A subset of these TNFR2 binders were found to agonise the receptor, inducing iκ-B degradation and NF-κB pathway signalling in vitro. TNFR2 was found to be expressed by tumor-infiltrating Treg cells, and to a lesser extent Teff cells, from three lung cancer patients, and a similar pattern was also observed in mice implanted with CT26 syngeneic tumors. In such animals, TNFR2-specific agonists inhibited tumor growth, enhanced tumor infiltration by CD8+ T cells and increased CD8+ T cell IFN-γ synthesis. Together, these data indicate a novel mechanism for TNF-α-independent TNFR2 agonism in cancer immunotherapy, and demonstrate the utility of target-agnostic screening in highlighting important targets during drug discovery.GW, BM, SG, JC-U, AS, AG-M, CB, JJ, RL, AJL, SR, RS, LJ, VV-A, RM and RWW were funded by MedImmune; JP and VB were funded by AstraZeneca PLC; JW, RSA-L and JB were funded by NIHR Cambridge Biomedical Research Centre and Kidney Research UK; JS and JF were funded by Retrogenix Ltd

Exo1 and Rad24 Differentially Regulate Generation of ssDNA at Telomeres of Saccharomyces cerevisiae cdc13-1 Mutants

Cell cycle arrest in response to DNA damage depends upon coordinated interactions between DNA repair and checkpoint pathways. Here we examine the role of DNA repair and checkpoint genes in responding to unprotected telomeres in budding yeast cdc13-1 mutants. We show that Exo1 is unique among the repair genes tested because like Rad9 and Rad24 checkpoint proteins, Exo1 inhibits the growth of cdc13-1 mutants at the semipermissive temperatures. In contrast Mre11, Rad50, Xrs2, and Rad27 contribute to the vitality of cdc13-1 strains grown at permissive temperatures, while Din7, Msh2, Nuc1, Rad2, Rad52, and Yen1 show no effect. Exo1 is not required for cell cycle arrest of cdc13-1 mutants at 36° but is required to maintain arrest. Exo1 affects but is not essential for the production of ssDNA in subtelomeric Y′ repeats of cdc13-1 mutants. However, Exo1 is critical for generating ssDNA in subtelomeric X repeats and internal single-copy sequences. Surprisingly, and in contrast to Rad24, Exo1 is not essential to generate ssDNA in X or single-copy sequences in cdc13-1 rad9Δ mutants. We conclude that Rad24 and Exo1 regulate nucleases with different properties at uncapped telomeres and propose a model to explain our findings

MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants

MRX, an evolutionally conserved DNA damage response complex composed of Mre11, Rad50 and Xrs2, is involved in DNA double strand break (DSB) repair, checkpoint activation and telomere maintenance. At DSBs, MRX plays a role in generating single stranded DNA (ssDNA) and signalling cell cycle arrest. Here we investigated whether MRX also contributes to generating ssDNA or signalling cell cycle arrest at uncapped telomeres. To investigate the role of MRX, we generated a conditionally degradable Rad50 protein and combined this with cdc13-1, a temperature sensitive mutation in the Cdc13 telomere capping protein. We show that Rad50 does not contribute to ssDNA generation or cell cycle arrest in response to cdcl3-1 uncapped telomeres. Instead, we find that Rad50 inhibits ssDNA accumulation and promotes cdc13-1 cell viability, consistent with a major role for MRX in telomere capping

Photolysis of dicamba (3,6-dichloro-2-methoxybenzoic acid) in aqueous solution and dispersed on solid supports

Dicamba (3,6-dichloro-2-methoxybenzoic acid) was exposed to UV light in aqueous solution. It was also irradiated in the solid phase without support or adsorbed on laponite (a synthetic clay) and ferric oxide

Consumer behaviour in the prediction of postharvest losses reduction for fresh strawberries packed in modified atmosphere packaging

MAP can maintain the storage life of products and thereby reduce food losses. However, the benefits of MAP for reducing losses is not well quantified, especially in relation with practices in the postharvest chain. This paper proposes an innovative approach, at the intersection between the domains of food engineering, social sciences and humanities and computer science to quantify the real benefit of using MAP in the postharvest chain of fresh strawberries. To take into account the diversity of postharvest storage conditions and consumer practices on reduction of food losses, 132 scenarios for storage of fresh strawberries were investigated with a numerical model and used as inputs to calculate the losses generated in the postharvest chain as a function of product deterioration. Considering the probability of occurrence of each scenario and consumer practices, the use of MAP instead of commercial macro-perforated packaging, would lead to 17 % reduction of losses on average. The losses reduction is low because 50 % of consumers open the packaging before storing the fruit into the refrigerator, disrupting the benefit of MAP before the fruit is consumed. Losses would be reduced by as much as 74 % if all the consumers stored the strawberries in the fridge and kept the MAP intact

Mechanically stable and photocatalytically active TiO2/SiO2 hybrid films on flexible organic substrates

SSCI-VIDE+CARE+DAG:IBE:CGUInternational audiencePhotocatalytic porous coatings (micro-, meso- and macroporous) are obtained by the dispersion of TiO2 nanoparticles in sol–gel hybrid matrices. The sol–gel silica matrix is used as a binder stabilizing the nanoparticle dispersion and as a protective layer for the organic substrates. Organic groups are introduced into the matrix to induce the film flexibility and a part of them is used to create the final microstructure allowing remarkable improvement of the photocatalytic properties. The film structure and UV stability are fully characterized. The photocatalytic activity is evaluated through a test with formic acid. Flexible efficient photoactive composites are obtained showing important capabilities for depollution (water and air) and self-cleaning applications

Ultrasound-assisted extraction of R-phycoerythrin from Grateloupia turuturu with and without enzyme addition

The aim of this study was to compare two processes for the extraction of R-phycoerythrin (R-PE) from the red seaweed Grateloupia turuturu: ultrasound-assisted extraction (UAE) and ultrasound-assisted enzymatic hydrolysis (UAEH). Process efficiencies were both evaluated by the yield of R-PE extraction and by the level of liquefaction. Experiments were conducted at 40 and 22 °C, for 6 h, using an enzymatic cocktail and an original ultrasonic flow-through reactor. R-PE appeared very sensitive to temperature, thus 22 °C is strongly recommended for its extraction by UAEH or UAE. However, the higher processing temperature (40 °C) clearly increased the extraction of water-soluble compounds (up to 91% of liquefaction). These two new processes are thus promising alternatives for the extraction of water-soluble components including R-PE, from wet seaweeds, with extraction yields at least similar to conventional solid–liquid extraction

Consumer perception data and scientific arguments about food packaging functionalities for fresh strawberries

This data article contains data characterizing consumer perception and scientific arguments about food packaging functionalities for fresh strawberries. These data are associated with the article “Choice of environment-friendly food packagings through argumentation systems and preferences” (see Yun et al., 2018). These data are stored in a public repository structured by an ontology. These data could be retrieved through the @Web tool, user-friendly interface to capitalize and query data (Buche et al., 2013; Guillard et al., 2017). The @Web tool is accessible online at http://pfl.grignon.inra.fr/atWeb/