Response of pseudomonas putida KT2440 to phenol at the level of membrane proteome

This study led to the extension and refinement of our current model for the global response of Pseudomonas putida KT2440 to phenol by getting insights into the adaptive response mechanisms involving the membrane proteome. A two-dimensional gel electrophoresis based protocol was optimized to allow the quantitative comparison of membrane proteins, by combining inner and outer membrane fractionation with membrane protein solubilization using the detergent dodecylmaltoside. Following phenol exposure, a coordinate increased content of protein subunits of known or putative solvent efflux pump systems (e.g. TtgA, TtgC, Ttg2A, Ttg2C, and PP_1516-7) and a decreased content of porins OprB, OprF, OprG and OprQ was registered, consistent with an adaptive response to reduce phenol intracellular concentration. This adaptive response may in part be mediated by post-translational modifications, as suggested by the relative content of the multiple forms identified for a few porins and efflux pump subunits. Results also suggest the important role of protein chaperones, of cell envelope and cell surface and of a more active respiratory chain in the response to phenol. All these mechanistic insights may be extended to Pseudomonas adaptation to solvents, of possible impact in biodegradation, bioremediation and biocatalysis.PhD scholarship SFRH/BD/38805/200

Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction

Jets and High-Et Phenomena

The working group on jets and high-Et phenomena of the Future physics at HERA Workshop studied subjects ranging from next-to-leading order (NLO) corrections in deeply inelastic scattering (DIS) and photoproduction with the corresponding determinations of physical quantities, to the physics of instanton-induced processes, where a novel non-perturbative manifestation of QCD could be observed. Other centres of interest were the physics of the forward direction, the tuning of event generators and the development of a new generator which includes a consistent treatment of the small- and large-$x$ QCD evolution. The recommendations of the working group concerning detector upgrades and machine luminosity are summarized

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

A SITUATION AWARENESS DRIVEN DESIGN FOR PREDICTIVE MAINTENANCE SYSTEMS: THE CASE OF OIL AND GAS PIPELINE OPERATIONS

The acquisition and processing of events from sensors or enterprise applications in real-time represent an essential part of many application domains such as the Internet of Things (IoT), offering benefits to predict the future condition of equipment to prevent the occurrence of failures. Many organisations already use some form of predictive maintenance to monitor performance or keep track of emerging business situations. However, the optimal design of applications to allow an effective Predictive Mainte-nance System (PMS) capable of analysing and processing large amounts of data is only scarcely exam-ined by Information Systems (IS) research. Due to the number, frequency, and the need for near-real-time evaluation systems must be capable of detecting complex event patterns based on spatial, temporal, or causal relationships on data streams (i.e. via Complex Event Processing). At the same time, however, due to the technical complexity, available systems today are static, since the creation and adaptation of recognisable situations results in slow development cycles. In addition, technical feasibility is only one prerequisite for predictive maintenance. Users must be capable of processing this vast amount of data presented without considerable cognitive effort. Precisely this challenge is even more daunting as op-erational maintenance personnel have to manage business-critical decisions with increasing frequency and short time. Research in Human Factors (HF) suggests Situation Awareness (SA) as a crucial sys-tem’s design paradigm allowing human beings to understand and anticipate the information available effectively. Building on this concept, this paper proposes a PMS for promoting operational decision makers’ Situation Awareness by three design principles (DP): Sensing, Acting, and Tracking. Based on these DPs, we implemented a PMS prototype for a scenario in Oil and Gas pipeline operations. Our finding suggest that the use of SA is of particular interest in realizing effective PMS

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph

Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition

Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor subunit cytokine receptor–like factor 2 (CRLF2), and other tumors with constitutive JAK2 signaling. In this study, we identify G935R, Y931C, and E864K mutations within the JAK2 kinase domain that confer resistance across a panel of JAK inhibitors, whether present in cis with JAK2 V617F (observed in MPNs) or JAK2 R683G (observed in B-ALL). G935R, Y931C, and E864K do not reduce the sensitivity of JAK2-dependent cells to inhibitors of heat shock protein 90 (HSP90), which promote the degradation of both wild-type and mutant JAK2. HSP90 inhibitors were 100–1,000-fold more potent against CRLF2-rearranged B-ALL cells, which correlated with JAK2 degradation and more extensive blockade of JAK2/STAT5, MAP kinase, and AKT signaling. In addition, the HSP90 inhibitor AUY922 prolonged survival of mice xenografted with primary human CRLF2-rearranged B-ALL further than an enzymatic JAK2 inhibitor. Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors

The role of lysine palmitoylation/myristoylation in the function of the TEAD transcription factors

The TEAD transcription factors are the most downstream elements of the Hippo pathway. Their transcriptional activity is modulated by different regulator proteins and by the palmitoylation/myristoylation of a specific cysteine residue. In this report, we show that a conserved lysine present in these transcription factors can also be acylated, probably following the intramolecular transfer of the acyl moiety from the cysteine. Using Scalloped (Sd), the Drosophila homolog of human TEAD, as a model, we designed a mutant protein (Glu352Gln Sd ) that is predominantly acylated on the lysine (Lys350 Sd ). This protein binds in vitro to the three Sd regulators-Yki, Vg and Tgi-with a similar affinity as the wild type Sd, but it has a significantly higher thermal stability than Sd acylated on the cysteine. This mutant was also introduced in the endogenous locus of the sd gene in Drosophila using CRISPR/Cas9. Homozygous mutants reach adulthood, do not present obvious morphological defects and the mutant protein has both the same level of expression and localization as wild type Sd. This reveals that this mutant protein is both functional and able to control cell growth in a similar fashion as wild type Sd. Therefore, enhancing the lysine acylation of Sd has no detrimental effect on the Hippo pathway. However, we did observe a slight but significant increase of wing size in flies homozygous for the mutant protein suggesting that a higher acylation of the lysine affects the activity of the Hippo pathway. Altogether, our findings indicate that TEAD/Sd can be acylated either on a cysteine or on a lysine, and suggest that these two different forms may have similar properties in cells

ZnS Ultrathin interfacial layers for optimizing carrier management in Sb2S3-based photovoltaics

Antimony chalcogenides represent a family of materials of low toxicity and relative abundance, with a high potential for future sustainable solar energy conversion technology. However, solar cells based on antimony chalcogenides present open-circuit voltage losses that limit their efficiencies. These losses are attributed to several recombination mechanisms, with interfacial recombination being considered as one of the dominant processes. In this work, we exploit atomic layer deposition (ALD) to grow a series of ultrathin ZnS interfacial layers at the TiO2/Sb2S3 interface to mitigate interfacial recombination and to increase the carrier lifetime. ALD allows for very accurate control over the ZnS interlayer thickness on the ångström scale (0-1.5 nm) and to deposit highly pure Sb2S3. Our systematic study of the photovoltaic and optoelectronic properties of these devices by impedance spectroscopy and transient absorption concludes that the optimum ZnS interlayer thickness of 1.0 nm achieves the best balance between the beneficial effect of an increased recombination resistance at the interface and the deleterious barrier behavior of the wide-bandgap semiconductor ZnS. This optimization allows us to reach an overall power conversion efficiency of 5.09% in planar configuration

Long-Living Holes in Grey Anatase TiO2 Enable Noble-Metal-Free and Sacrificial-Agent-Free Water Splitting

Titanium dioxide has been the benchmark semiconductor in photocatalysis for more than 40 years. Full water splitting, that is, decomposing water into H2 and O2 in stoichiometric amounts and with an acceptable activity, still remains a challenge, even when TiO2-based photocatalysts are used in combination with noble-metal co-catalysts. The bottleneck of anatase-type TiO2 remains the water oxidation, that is, the hole transfer reaction from pristine anatase to the aqueous environment. In this work, we report that “grey” (defect engineered) anatase can provide a drastically enhanced lifetime of photogenerated holes, which, in turn, enables an efficient oxidation reaction of water to peroxide via a two-electron pathway. As a result, a Ni@grey anatase TiO2 catalyst can be constructed with an impressive performance in terms of photocatalytic splitting of neutral water into H2 and a stoichiometric amount of H2O2 without the need of any noble metals or sacrificial agents. The finding of long hole lifetimes in grey anatase opens up a wide spectrum of further photocatalytic applications of this material. © 2020 The Authors. Published by Wiley-VCH Gmb