Cytokine Profiling in Myeloproliferative Neoplasms: Overview on Phenotype Correlation, Outcome Prediction, and Role of Genetic Variants

Among hematologic malignancies, the classic Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are considered a model of inflammation-related cancer development. In this context, the use of immune-modulating agents has recently expanded the MPN therapeutic scenario. Cytokines are key mediators of an auto-amplifying, detrimental cross-talk between the MPN clone and the tumor microenvironment represented by immune, stromal, and endothelial cells. This review focuses on recent advances in cytokine-profiling of MPN patients, analyzing different expression patterns among the three main Philadelphia-negative (Ph-negative) MPNs, as well as correlations with disease molecular profile, phenotype, progression, and outcome. The role of the megakaryocytic clone as the main source of cytokines, particularly in myelofibrosis, is also reviewed. Finally, we report emerging intriguing evidence on the contribution of host genetic variants to the chronic pro-inflammatory state that typifies MPNs

Anomalous RR Lyrae stars(?). III. CM Leonis

Time series of B,V,I CCD photometry and radial velocity measurements from high resolution spectroscopy (R=30,000) covering the full pulsation cycle are presented for the field RR Lyrae star CM Leonis. The photometric data span a 6 year interval from 1994 to 1999, and allow us to firmly establish the pulsation mode and periodicity of the variable. The derived period P=0.361699 days (+/- 0.000001) is very close to the value published in the Fourth Edition of the General Catalogue of Variable Stars (P=0.361732 days). However, contrary to what was previously found, the amplitude and shape of the light curve qualify CM Leo as a very regular first overtone pulsator with a prominent hump on the rising branch of its multicolour light curves. According to an abundace analysis performed on three spectra taken near minimum light (0.42 < phase < 0.61), CM Leo is a metal-poor star with metal abundance [Fe/H]=-1.93 +/- 0.20. The photometric and radial velocity curves of CM Leo have been compared with the predictions of suitable pulsational models to infer tight constraints on the stellar mass, effective temperature, and distance modulus of the star. We derive a true distance modulus of CM Leo of (m-M)0=13.11 +/- 0.02 mag and a corresponding absolute magnitude of Mv=0.47 +/- 0.04. This absolute magnitude, once corrected for evolutionary and metallicity effects, leads to a true distance modulus of the Large Magellanic Cloud of (m-M)0=18.43 +/- 0.06 mag, in better agreement with the long astronomical distance scale.Comment: 14 pages, 10 figures, accepted for publication in MNRA

A New Wood Surface Flame-Retardant Based on Poly-m-Aramid Electrospun Nanofibers

Poly(meta-phenylene isophtalamide) (PMIA) was processed via electrospinning to provide nanofibrous membranes with randomly and aligned fibers. Mechanical performance of such membranes was evaluated, applying a normalization procedure that takes into account the peculiar morphology of such complex substrate where voids can sum up to almost 80% of the sample volume. Random and aligned fibers membranes are applied onto wood panels to test their fire resistance in cone calorimetry when coated in polyaramidic thin nanofiber mats. Tests highlighted that random fibers provide a better fire protection, increasing Time to Ignition and decreasing the Fire Performance Index. Another important parameter affecting the performance is the adhesive system used to apply the nanofibers onto wood that is able to significantly modify the fire performance of the polyaramidic-coated wood panels. POLYM. ENG. SCI., 2019. (c) 2019 Society of Plastics Engineer

Genome-wide analysis of the PreA/PreB (QseB/QseC) regulon of Salmonella enterica serovar Typhimurium

<p>Abstract</p> <p>Background</p> <p>The <it>Salmonella </it>PreA/PreB two-component system (TCS) is an ortholog of the QseBC TCS of <it>Escherichia coli</it>. In both <it>Salmonella </it>and <it>E. coli</it>, this system has been shown to affect motility and virulence in response to quorum-sensing and hormonal signals, and to affect the transcription of the <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium) <it>pmrAB </it>operon, which encodes an important virulence-associated TCS.</p> <p>Results</p> <p>To determine the PreA/PreB regulon in <it>S</it>. Typhimurium, we performed DNA microarrays comparing the wild type strain and various <it>preA </it>and/or <it>preB </it>mutants in the presence of ectopically expressed <it>preA </it>(<it>qseB</it>). These data confirmed our previous findings of the negative effect of PreB on PreA gene regulation and identified candidate PreA-regulated genes. A proportion of the activated loci were previously identified as PmrA-activated genes (<it>yibD</it>, <it>pmrAB</it>, <it>cptA</it>, etc.) or were genes located in the local region around <it>preA</it>, including the <it>preAB </it>operon. The transcriptional units were defined in this local region by RT-PCR, suggesting three PreA activated operons composed of <it>preA-preB</it>, <it>mdaB-ygiN</it>, and <it>ygiW</it>-STM3175. Several putative virulence-related phenotypes were examined for <it>preAB </it>mutants, resulting in the observation of a host cell invasion and slight virulence defect of a <it>preAB </it>mutant. Contrary to previous reports on this TCS, we were unable to show a PreA/PreB-dependent effect of the quorum-sensing signal AI-2 or of epinephrine on <it>S</it>. Typhimurium with regard to bacterial motility.</p> <p>Conclusion</p> <p>This work further characterizes this unorthadox OmpR/EnvZ class TCS and provides novel candidate regulated genes for further study. This first in-depth study of the PreA/PreB regulatory system phenotypes and regulation suggests significant comparative differences to the reported function of the orthologous QseB/QseC in <it>E. coli</it>.</p

Modulation of the Akt/Ras/Raf/MEK/ERK pathway by A3 adenosine receptor

Downstream A3 receptor signalling plays an important role in the regulation of cell death and proliferation. Therefore, it is important to determine the molecular pathways involved through A3 receptor stimulation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt and the Raf/mitogen-activated protein kinase (MAPK/ERK) kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways have central roles in the regulation of cell survival and proliferation. The crosstalk between these two pathways has also been investigated. The focus of this review centres on downstream mediators of A3 adenosine receptor signalling

IDeS Method Applied to an Innovative Motorbike—Applying Topology Optimization and Augmented Reality

This study is on the conception of the DS700 HYBRID project by the application of the Industrial Design Structure method (IDeS), which applies different tools sourced from engineering and style departments, including QFD and SDE, used to create the concept of a hybrid motorbike that could reach the market in the near future. SDE is an engineering approach for the design and development of industrial design projects, and it finds important applications in the automotive sector. In addition, analysis tools such as QFD, comprising benchmarking and top-flop analysis are carried out to maximize the creative process. The key characteristics of the bike and the degree of innovation are identified and outlined, the market segment is identified, and the stylistic trends that are most suitable for a naked motorbike of the future are analyzed. In the second part the styling of each superstructure and of all the components of the vehicle is carried out. Afterwards the aesthetics and engineering perspectives are accounted for to complete the project. This is achieved with modelling and computing tools such as 3D CAD, visual renderings, and FEM simulations, and virtual prototyping thanks to augmented reality (AR), and finally physical prototyping with the use of additive manufacturing (AM). The result is a product conception able to compete in the present challenging market, with a design that is technically feasible and also reaches new lightness targets for efficiency

Pharmacological characterization of P2X1 and P2X3 purinergic receptors in bovine chondrocytes

SummaryObjectiveThe aim of the present study is that of characterizing, for the first time in a quantitative way, from a biochemical, physico chemical and functional point of view P2X1 and P2X3 purinergic receptors in bovine chondrocytes. The affinity and the potency of typical purinergic ligands were studied through competition binding experiments and their role in modulating chondrocyte actvities was investigated by analyzing nitric oxide (NO) and prostaglandin E2 (PGE2) release.MethodsSaturation, competition binding experiments, western blotting and immunohistochemistry assays on the P2X1 and P2X3 purinergic receptors in bovine chondrocytes were performed. Thermodynamic analysis of the P2X1 and P2X3 purinergic binding was studied to investigate the forces driving drug-receptor coupling. In the functional assays (NO and PGE2 release) the potency of purinergic agonists and antagonists was evaluated.ResultsBovine chondrocytes expressed P2X1 and P2X3 purinergic receptors and thermodynamic parameters indicated that purinergic binding is enthalpy- and entropy-driven for agonists and totally entropy-driven for antagonists. Typical purinergic agonists such as adenosine 5′-triphosphate (ATP) and α,β-methyleneATP were able to increase NO and PGE2 release. A purinergic antagonist, A317491, was able to block the stimulatory effect on functional experiments mediated by the agonists.ConclusionsThese data demonstrate for the first time the presence of functional P2X1 and P2X3 purinergic receptors in bovine chondrocytes. Agonists and antagonists are thermodynamically discriminated and are able to modulate functional responses such as NO and PGE2 release. These results suggest the potential role of novel purinergic antagonists in the treatment of pathophysiological diseases linked to the inflammation and involved in articular cartilage resorption

The ESO Slice Project (ESP) galaxy redshift survey: III. The Sample

The ESO Slice Project (ESP) is a galaxy redshift survey extending over about 23 square degrees, in a region near the South Galactic Pole. The survey is ~85% complete to the limiting magnitude b_J=19.4 and consists of 3342 galaxies with redshift determination. The ESP survey is intermediate between shallow, wide angle samples and very deep, one-dimensional pencil beams; the spanned volume is ~ 5 x 10^4 Mpc^3 at the sensitivity peak (z ~ 0.1). In this paper we present the description of the observations and of the data reduction, the ESP redshift catalogue and the analysis of the quality of the velocity determinations.Comment: 10 pages, 4 encapsulated figures, uses A&A LATEX; A&A Supplements in press (June 1998 issue