Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs’ ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

Der Begriff der Individualisierung trägt in der Regel negative Konnotationen: sei es im Hinblick auf eine zunehmende Vereinzelung und Vereinsamung von Individuen oder hinsichtlich der Zunahme egoistisch anmutender Handlungen von Menschen, die das Gemeinwohl aus dem Blick verlieren. Prozesse der Individualisierung werden daher häufig als Bedrohung für die Konstituierung moderner Gesellschaften diskutiert. Diese Studie hingegen präsentiert eine neue Lesart der Individualisierung. Orientiert an Niklas Luhmanns Arbeiten und gestützt auf Ergebnisse einer empirischen Studie legt Bettina-Johanna Krings eine soziologische Betrachtung vor, die die Aufforderung zur Individualisierung als eine notwendige Herausforderung in modernen Gesellschaften interpretiert.

In this work, peptides designed to selectively interact with cellular receptors involved in the regulation of angiogenesis were anchored to oligo-ethylene glycol-capped gold nanoparticles (AuNPs) and used to evaluate the modulation of vascular development using an ex ovo chick chorioallantoic membrane assay. These nanoparticles alter the balance between naturally secreted pro- and antiangiogenic factors, under various biological conditions, without causing toxicity. Exposure of chorioallantoic membranes to AuNP-peptide activators of angiogenesis accelerated the formation of new arterioles when compared to scrambled peptide-coated nanoparticles. On the other hand, antiangiogenic AuNP-peptide conjugates were able to selectively inhibit angiogenesis in vivo. We demonstrated that AuNP vectorization is crucial for enhancing the effect of active peptides. Our data showed for the first time the effective control of activation or inhibition of blood vessel formation in chick embryo via AuNP-based formulations suitable for the selective modulation of angiogenesis, which is of paramount importance in applications where promotion of vascular growth is desirable (eg, wound healing) or ought to be contravened, as in cancer development.

In this study, we report solution-processed amorphous zinc tin oxide transistors exhibiting high operational stability under positive gate bias stress, translated by a recoverable threshold voltage shift of about 20{%} of total applied stress voltage. Under vacuum condition, the threshold voltage shift saturates showing that the gate-bias stress is limited by trap exhaustion or balance between trap filling and emptying mechanism. In ambient atmosphere, the threshold voltage shift no longer saturates, stability is degraded and the recovering process is impeded. We suggest that the trapping time during the stress and detrapping time in recovering are affected by oxygen adsorption/desorption processes. The time constants extracted from stretched exponential fitting curves are ≈106 s and 105 s in vacuum and air, respectively.

Here we present for the first time a TiO2/Cu2O all-oxide heterojunction solar cell entirely produced by spray pyrolysis onto fluorine doped tin oxide (FTO) covered glass substrates, using silver as a back contact. A combinatorial approach was chosen to investigate the impact of the TiO2 window layer and the Cu2O light absorber thicknesses. We observe an open circuit voltage up to 350mV and a short circuit current density which is strongly dependent of the Cu2O thickness, reaching a maximum of {\~{}}0.4mA/cm2. Optical investigation reveals that a thickness of 300nm spray pyrolysis deposited Cu2O is sufficient to absorb most photons with an energy above the symmetry allowed optical transition of 2.5eV, indicating that the low current densities are caused by strong recombination in the absorber that consists of small Cu2O grains.

Electric vehicles (EVs) are considered alternatives to internal combustion engines due to their energy efficiency and contribution to CO2 mitigation. The adoption of EVs depends on consumer preferences, including cost, social status and driving habits, although it is agreed that current and expected costs play a major role. We use a partial equilibrium model that minimizes total energy system costs to assess whether EVs can be a cost-effective option for the consumers of each EU27 member state up to 2050, focusing on the impact of different vehicle investment costs and CO2 mitigation targets. We found that for an EU-wide greenhouse gas emission reduction cap of 40% and 70% by 2050 vis-à-vis 1990 emissions, battery electric vehicles (BEVs) are cost-effective in the EU only by 2030 and only if their costs are 30% lower than currently expected. At the EU level, vehicle costs and the capability to deliver both short- and long-distance mobility are the main drivers of BEV deployment. Other drivers include each state’s national mobility patterns and the cost-effectiveness of alternative mitigation options, both in the transport sector, such as plug-in hybrid electric vehicles (PHEVs) or biofuels, and in other sectors, such as renewable electricity.

Transcription is a highly dynamic process. Consequently, we have developed native elongating transcript sequencing technology for mammalian chromatin (mNET-seq), which generates single-nucleotide resolution, nascent transcription profiles. Nascent RNA was detected in the active site of RNA polymerase II (Pol II) along with associated RNA processing intermediates. In particular, we detected 5'splice site cleavage by the spliceosome, showing that cleaved upstream exon transcripts are associated with Pol II CTD phosphorylated on the serine 5 position (S5P), which is accumulated over downstream exons. Also, depletion of termination factors substantially reduces Pol II pausing at gene ends, leading to termination defects. Notably, termination factors play an additional promoter role by restricting non-productive RNA synthesis in a Pol II CTD S2P-specific manner. Our results suggest that CTD phosphorylation patterns established for yeast transcription are significantly different in mammals. Taken together, mNET-seq provides dynamic and detailed snapshots of the complex events underlying transcription in mammals.

Abstract The green fluorescent protein (GFP) is a useful indicator in a broad range of applications including cell biology, gene expression and biosensing. However, its full potential is hampered by the lack of a selective, mild and low-cost purification scheme. In order to address this demand, a novel adsorbent was developed as a generic platform for the purification of \{GFP\} or \{GFP\} fusion proteins, giving \{GFP\} a dual function as reporter and purification tag. After screening a solid-phase combinatorial library of small synthetic ligands based on the Ugi-reaction, the lead ligand (A4C7) selectively recovered \{GFP\} with 94% yield and 94% purity under mild conditions and directly from Escherichia coli extracts. Adsorbents containing the ligand \{A4C7\} maintained the selectivity to recover other proteins fused to GFP. The performance of \{A4C7\} adsorbents was compared with two commercially available methods (immunoprecipitation and hydrophobic interaction chromatography), confirming the new adsorbent as a low-cost viable alternative for \{GFP\} purification.

Three iron(III) complexes with ligands derived from N-ethyl-N-(2-aminoethyl) salicylaldiminate (H, 1; 5-Br, 2; 3-OMe, 3 substituents at the phenyl group) were prepared and the X-ray crystal structures of 1 and 2 are reported. NMR studies of solutions of these complexes in DMSO allowed for investigation of their magnetic behaviour and paramagnetic relaxation contribution. The relaxivities measured ranged from 0.35 to 0.80 mM(-1) s(-1) for proton Larmor frequencies from 0.01 to 300 MHz, in agreement with those known for other iron(III) based contrast agents. Biological studies on colonic epithelial T-84 cell monolayers showed that the compounds exert toxic effects only at concentrations higher than 100 mu M while coincidently reducing colonic epithelial secretory function. These two features make these complexes good candidates for further development in order to be used as MRI contrast agents. (C) 2015 Elsevier B.V. All rights reserved.

Nucleation is a critical step determining the outcome of the entire crystallization process. Finding an effective nucleant for protein crystallization is of utmost importance for structural biology. The latter relies on good-quality crystals to solve the three-dimensional structures of macromolecules. In this study we show that crystalline barium sulfate (BaSO4) with an etched and/or ionic liquid (IL)-functionalized surface (1) can induce protein nucleation at concentrations well below the concentration needed to promote crystal growth under control conditions, (2) can shorten the nucleation time, (3) can increase the growth rate, and finally (4) may help to improve the protein crystal morphology. These effects were shown for lysozyme, RNase A, trypsin, proteinase K, myoglobin, and hemoglobin. Therefore, the use of BaSO4 particles enables us to reduce the amount of protein in crystallization trials and increases the chance of obtaining protein crystals of the desired quality. In the context of the underlying mechanism, it is shown that the protein-solid contact formation is governed by the interaction of the polar compartments of the biomacromolecule with the support. The tendency of a protein to concentrate near the solid surface is enhanced by both the hydrophobicity of the protein and that of the surface (tuned by the functionalizing IL). These mechanisms of interaction of biomacromolecules with inorganic hydrophilic solids correspond to the principles of amphiphilic IL-mineral interactions.

Abstract Humic substances (HS) constitute a significant fraction of natural organic matter in terrestrial and aquatic environments and can act as terminal electron acceptors in anaerobic microbial respiration. Geobacter sulfurreducens has a remarkable respiratory versatility and can utilize the \{HS\} analog anthraquinone-2,6-disulfonate (AQDS) as a terminal electron acceptor or its reduced form (AH2QDS) as an electron donor. Previous studies set the triheme cytochrome PpcA as a key component for \{HS\} respiration in G. sulfurreducens, but the process is far from fully understood. In this work, \{NMR\} chemical shift perturbation measurements were used to map the interaction region between PpcA and AH2QDS, and to measure their binding affinity. The results showed that the \{AH2QDS\} binds reversibly to the more solvent exposed edge of PpcA heme IV. The \{NMR\} and visible spectroscopies coupled to redox measurements were used to determine the thermodynamic parameters of the PpcA:quinol complex. The higher reduction potential of heme İV\} (− 127 mV) compared to that of \{AH2QDS\} (− 184 mV) explains why the electron transfer is more favorable in the case of reduction of the cytochrome by the quinol. The clear evidence obtained for the formation of an electron transfer complex between \{AH2QDS\} and PpcA, combined with the fact that the protein also formed a redox complex with AQDS, revealed for the first time the bifunctional behavior of PpcA toward an analog of the HS. Such behavior might confer selective advantage to G. sulfurreducens, which can utilize the \{HS\} in any redox state available in the environment for its metabolic needs.