Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

Introducing fluorescence-guided surgery for pediatric Ewing, osteo-, and Rhabdomyosarcomas: a literature review

Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.Experimentele farmacotherapi

An Inside Look at Sunspot Oscillations with Higher Azimuthal Wavenumbers

Solar chromospheric observations of sunspot umbrae offer an exceptional view of magneto-hydrodynamic wave phenomena. In recent years, a wealth of wave signatures related to propagating magneto-acoustic modes have been presented, which demonstrate complex spatial and temporal structuring of the wave components. Theoretical modelling has demonstrated how these ubiquitous waves are consistent with an m=0 slow magneto-acoustic mode, which are excited by trapped sub-photospheric acoustic (p-mode) waves. However, the spectrum of umbral waves is broad, suggesting that the observed signatures represent the superposition of numerous frequencies and/or modes. We apply Fourier filtering, in both spatial and temporal domains, to extract chromospheric umbral wave characteristics consistent with an m=1 slow magneto-acoustic mode. This identification has not been described before. Angular frequencies of 0.037 +/- 0.007 rad/s (2.1 +/- 0.4 deg/s), corresponding to a period approximately 170 s for the m=1 mode are uncovered for spatial wavenumbers in the range of 0.45<k<0.90 arcsec^-1 (5000-9000 km). Theoretical dispersion relations are solved, with corresponding eigenfunctions computed, which allows the density perturbations to be investigated and compared with our observations. Such magnetohydrodynamic modelling confirms our interpretation that the identified wave signatures are the first direct observations of an m=1 slow magneto-acoustic mode in the chromospheric umbra of a sunspot

Environmentally Persistent Free Radicals (EPFRs). 3. Free versus Bound Hydroxyl Radicals in EPFR Aqueous Solutions

Additional experimental evidence is presented for in vitro generation of hydroxyl radicals because of redox cycling of environmentally persistent free radicals (EPFRs) produced after adsorption of 2-monochlorophenol at 230 °C (2-MCP-230) on copper oxide supported by silica, 5% Cu(II)O/silica (3.9% Cu). A chemical spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), in conjunction with electron paramagnetic resonance (EPR) spectroscopy was employed. Experiments in spiked O17 water have shown that ∼15% of hydroxyl radicals formed as a result of redox cycling. This amount of hydroxyl radicals arises from an exogenous Fenton reaction and may stay either partially trapped on the surface of particulate matter (physisorbed or chemisorbed) or transferred into solution as free OH. Computational work confirms the highly stable nature of the DMPO–OH adduct, as an intermediate produced by interaction of DMPO with physisorbed/chemisorbed OH (at the interface of solid catalyst/solution). All reaction pathways have been supported by ab initio calculations

Neutron spectroscopy of 26Mg states : Constraining the stellar neutron source 22Ne(α,n)25Mg

This work reports on accurate, high-resolution measurements of the 25Mg(n,γ)26Mg and 25Mg(n,tot) cross sections in the neutron energy range from thermal to about 300 keV, leading to a significantly improved 25Mg(n,γ)26Mg parametrization. The relevant resonances for n+25Mg were characterized from a combined R-matrix analysis of the experimental data. This resulted in an unambiguous spin/parity assignment of the corresponding excited states in 26Mg. With this information experimental upper limits of the reaction rates for 22Ne(α,n)25Mg and 22Ne(α,γ)26Mg were established, potentially leading to a significantly higher (α,n)/(α,γ) ratio than previously evaluated. The impact of these results has been studied for stellar models in the mass range 2 to 25 M⊙

Neutron spectroscopy of ²⁶Mg states: Constraining the stellar neutron source ²²Ne(α,n)²⁵Mg

This work reports on accurate, high-resolution measurements of the 25Mg(n,γ)26Mg and 25Mg(n,tot) cross sections in the neutron energy range from thermal to about 300 keV, leading to a significantly improved 25Mg(n,γ)26Mg parametrization. The relevant resonances for n+25Mg were characterized from a combined R-matrix analysis of the experimental data. This resulted in an unambiguous spin/parity assignment of the corresponding excited states in 26Mg. With this information experimental upper limits of the reaction rates for 22Ne(α,n)25Mg and 22Ne(α,γ)26Mg were established, potentially leading to a significantly higher (α,n)/(α,γ) ratio than previously evaluated. The impact of these results has been studied for stellar models in the mass range 2 to 25 M⊙

Waterkwaliteit in Nederland; toestand (2012-2015) en trend (1992-2015) : Addendum bij rapport 2016-0019

Nitrogen and phosphorus are essential substances in manure used at farms to improve production. Nevertheless, too much nitrogen or phosphorus is harmful because the surplus can leach as a result of which the quality of ground and surface waters deteriorates. Too high concentrations in surface waters may cause, for example, algal blooms. The concentrations of nitrogen and phosphorus in ground and surface waters in 2015 are comparable with those in 2012-2014. This overview is a supplement to the overview published in 2016. In 2016, the concentrations in 2012-2014 and the trend in the period 1992-2014 were considered. The conclusions drawn in 2016 do not change when adding the 2015 data. The research is carried out by RIVM in co-operation with Rijkswaterstaat Water, Traffic and Environment (RWS/WVL) and the knowledge institute Deltares. This addendum has been pledged to the European Union. This addendum will also be used for the negotiations about the sixth Nitrate Directive Action Programme and the prolongation of the derogation for the period 2018-2021.Stikstof en fosfaat zijn essentiële stoffen in mest die landbouwbedrijven gebruiken om de productie van gewassen te bevorderen. Te veel stikstof en fosfaat is echter schadelijk omdat het teveel kan uitspoelen waardoor de kwaliteit van het grond- en oppervlaktewater slechter wordt. Te hoge concentraties in het oppervlaktewater kunnen bijvoorbeeld algenbloei veroorzaken. De concentraties van stikstof en fosfaat in het grond- en oppervlaktewater in 2015 zijn vergelijkbaar met die in de jaren 2012-2014. Dit blijkt uit een inventarisatie van de grond- en oppervlaktewaterkwaliteit in 2015. De inventarisatie is een aanvulling op de inventarisatie die in 2016 is gerapporteerd. In 2016 is gekeken naar de concentraties in 2012-2014 en de ontwikkeling in de periode 1992-2014. Door de cijfers over 2015 toe te voegen, ontstaan geen andere conclusies. De aanvullende inventarisatie is uitgevoerd door het RIVM met Rijkswaterstaat Water, Verkeer en Leefomgeving (RWS/WVL) en Deltares. Deze aanvulling op het eerdere rapport is toegezegd aan de Europese Commissie. Dit addendum dient mede voor de onderhandelingen over het zesde Nederlandse Nitraatrichtlijnactieprogramma en een derogatie voor de periode 2018-2021.Ministerie van I&M ; Ministerie van E

sp-sp(3) Coupling reactions of alkynylsilver cations, RC (equivalent to) CAg2+ (R = Me and Ph) with allyliodide

Alkynylsilver cations, RC equivalent to CAg2+ (where R = Me and Ph) have been prepared in the gas phase using multistage mass spectrometry experiments in a quadrupole ion trap mass spectrometer. Two methods were used: (i) electrospray ionisation (ESI) of a mixture of AgNO3 (in MeOH/H2O/acetic acid) and the alkyne carboxylic acid to yield the appropriate silver acetylide cations RC equivalent to CAg2+, via a facile decarboxylation of the RC equivalent to CCO2Ag2+ precursor; (ii) ESI of silver acetylides, RCuCAg, which yields a cluster of the type, [(RC equivalent to CAg) 12Ag2Cl](+). Regardless of the method of preparation, these alkynylsilver cations, RCuCAg2+, undergo ion-molecule reactions with allyliodide to yield the ionic products Ag(2)l(+) and [(RC equivalent to CCH2CH=CH2)Ag](+). The CID spectrum of [(PhC equivalent to CCH2CH=CH2)Ag](+) was compared to that of an authentic sample of the silver adduct of 5-phenyl-1-penten-4-yne. Both ions fragment to yield Ag+ and the radical cation, PhC equivalent to CCH2CH=CH2+., confirming that C-C bond coupling has taken place in the gas phase. DFT calculations were carried out on these C-C bond coupling reactions for the system R = Me. The reaction is highly exothermic and involves the initial coordination of the allyliodide to both silver atoms, with the iodine coordinating to one atom and the alkene moiety coordinating to the other. The overall mechanism of C-C bond coupling involves oxidative addition of the allyliodide followed by reductive elimination of RC equivalent to CCH2CH=CH2, to ultimately yield two sets of reaction products: (i) Ag(2)l(+) and RC equivalent to CCH2CH=CH2; and (ii) [(RC equivalent to CCH2CH=CH2)Ag](+) and Agl