De novo synthesis of diacylglycerol from glucose. A new pathway of signal transduction in human neutrophils stimulated during phagocytosis of beta-glucan particles.

The phagocytosis of beta-glucan particles by human neutrophils and the associated activation of NADPH O2- forming oxidase were accompanied by an increased hydrolysis of phosphoinositides by phospholipase C, hydrolysis of phosphatidylcholine by phospholipase D, accumulation of diglyceride (DG) mass, and [Ca2+]i rise. The reaction of phospholipid hydrolysis played a minor role in the formation of DG, which was mainly formed by de novo synthesis from glucose. The activation of this pathway was shown by the stimulation of the incorporation of [U-14C]glucose into DG, which occurred very rapidly after the challenge of neutrophils with beta-glucan particles. This DG derived from glucose was found almost completely as 1-acyl-2-acyl-glycerol (DAG). On the basis of the finding that phosphatidic acid was the precursor of DAG, an increase in the incorporation of [U-14C]acetate into DAG did not occur, and the [14C]radioactivity was in the glycerol backbone, the synthesis of DAG from [U-14C]glucose occurred very likely via dihydroxyacetone phosphate and glycerol 3-phosphate, stepwise acylation to phosphatidic acid, and dephosphorylation by phosphatidate phosphatase

Optical design and performance simulations for the 1.49 keV beamline of the BEaTriX X-ray facility

The BEaTriX (Beam Expander Testing X-ray) facility, now operational at INAF-Brera Astronomical Observatory, will represent a cornerstone in the acceptance roadmap of Silicon Pore Optics (SPO) mirror modules, and will so contribute to the final angular resolution of the ATHENA X-ray telescope. By expansion and collimation of a microfocus X-ray source via a paraboloidal mirror, a monochromation stage, and an asymmetric crystal, BEaTriX enables the full-aperture illumination of an SPO mirror module with a parallel, monochromatic, and broad (140 mm × 60 mm) X-ray beam. The beam then propagates in a 12 m vacuum range to image the point spread function of the mirror module, directly on a focal plane camera. Currently the 4.51 keV beamline, based on silicon crystals, is operational in BEaTriX. A second beamline at 1.49 keV, which requires a separate paraboloidal mirror and organic crystals (ADP) for beam expansion, is being realized. As for monochromators, the current design is based on asymmetric quartz crystals. In this paper, we show the current optical design of the 1.49 keV beamline and the optical simulations carried out to predict the achievable performances in terms of beam collimation, intensity, and uniformity. In the next future, the simulation activity will allow us to determine manufacturing and alignment tolerances for the optical components

Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions

Lignocellulose-based biorefineries have been gaining increasing attention to substitute current petroleum-based refineries. Biomass processing requires a pretreatment step to break lignocellulosic biomass recalcitrant structure, which results in the release of a broad range of microbial inhibitors, mainly weak acids, furans, and phenolic compounds. Saccharomyces cerevisiae is the most commonly used organism for ethanol production; however, it can be severely distressed by these lignocellulose-derived inhibitors, in addition to other challenging conditions, such as pentose sugar utilization and the high temperatures required for an efficient simultaneous saccharification and fermentation step. Therefore, a better understanding of the yeast response and adaptation towards the presence of these multiple stresses is of crucial importance to design strategies to improve yeast robustness and bioconversion capacity from lignocellulosic biomass. This review includes an overview of the main inhibitors derived from diverse raw material resultants from different biomass pretreatments, and describes the main mechanisms of yeast response to their presence, as well as to the presence of stresses imposed by xylose utilization and high-temperature conditions, with a special emphasis on the synergistic effect of multiple inhibitors/stressors. Furthermore, successful cases of tolerance improvement of S. cerevisiae are highlighted, in particular those associated with other process-related physiologically relevant conditions. Decoding the overall yeast response mechanisms will pave the way for the integrated development of sustainable yeast cell--based biorefineries.This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the strategic funding of UID/BIO/04469/2013 unit, MIT Portugal Program (Ph.D. grant PD/BD/128247/ 2016 to Joana T. Cunha), Ph.D. grant SFRH/BD/130739/2017 to Carlos E. Costa, COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE-01-0145-FEDER-000004), YeasTempTation (ERA-IB-2-6/0001/2014), and MultiBiorefinery project (POCI-01-0145-FEDER-016403). Funding by the Institute for Bioengineering and Biosciences (IBB) from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project N. 007317) was also receiveinfo:eu-repo/semantics/publishedVersio

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

First light of BEaTriX, the new testing facility for the modular X-ray optics of the ATHENA mission

Aims: The Beam Expander Testing X-ray facility (BEaTriX) is a unique X-ray apparatus now operated at the Istituto Nazionale di Astrofisica (INAF), Osservatorio Astronomico di Brera (OAB), in Merate, Italy. It has been specifically designed to measure the point spread function (PSF) and the effective area (EA) of the X-ray mirror modules (MMs) of the Advanced Telescope for High-ENergy Astrophysics (ATHENA), based on silicon pore optics (SPO) technology, for verification before integration into the mirror assembly. To this end, BEaTriX generates a broad, uniform, monochromatic, and collimated X-ray beam at 4.51 keV. The beam collimation is better than a few arcseconds, ensuring reliable tests of the ATHENA MMs, in their focus at a 12 m distance. Methods: In BEaTriX, a micro-focus X-ray source with a titanium anode is placed in the focus of a paraboloidal mirror, which generates a parallel beam. A crystal monochromator selects the 4.51 keV line, which is expanded to the final size by a crystal asymmetrically cut with respect to the crystalline planes. An in-house-built Hartmann plate was used to characterize the X-ray beam divergence, observing the deviation of X-ray beams from the nominal positions, on a 12-m-distant CCD camera. After characterization, the BEaTriX beam has the nominal dimensions of 170 mm × 60 mm, with a vertical divergence of 1.65 arcsec and a horizontal divergence varying between 2.7 and 3.45 arcsec, depending on the monochromator setting: either high collimation or high intensity. The flux per area unit varies from 10 to 50 photons/s/cm2 from one configuration to the other. Results: The BEaTriX beam performance was tested using an SPO MM, whose entrance pupil was fully illuminated by the expanded beam, and its focus was directly imaged onto the camera. The first light test returned a PSF and an EA in full agreement with expectations. As of today, the 4.51 keV beamline of BEaTriX is operational and can characterize modular X-ray optics, measuring their PSF and EA with a typical exposure of 30 min. Another beamline at 1.49 keV is under development and will be integrated into the current equipment. We expect BEaTriX to be a crucial facility for the functional test of modular X-ray optics, such as the SPO MMs for ATHENA

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Anaerobiosis revisited: growth of Saccharomyces cerevisiae under extremely low oxygen availability

The budding yeast Saccharomyces cerevisiae plays an important role in biotechnological applications, ranging from fuel ethanol to recombinant protein production. It is also a model organism for studies on cell physiology and genetic regulation. Its ability to grow under anaerobic conditions is of interest in many industrial applications. Unlike industrial bioreactors with their low surface area relative to volume, ensuring a complete anaerobic atmosphere during microbial cultivations in the laboratory is rather difficult. Tiny amounts of O2 that enter the system can vastly influence product yields and microbial physiology. A common procedure in the laboratory is to sparge the culture vessel with ultrapure N2 gas; together with the use of butyl rubber stoppers and norprene tubing, O2 diffusion into the system can be strongly minimized. With insights from some studies conducted in our laboratory, we explore the question ‘how anaerobic is anaerobiosis?’. We briefly discuss the role of O2 in non-respiratory pathways in S. cerevisiae and provide a systematic survey of the attempts made thus far to cultivate yeast under anaerobic conditions. We conclude that very few data exist on the physiology of S. cerevisiae under anaerobiosis in the absence of the anaerobic growth factors ergosterol and unsaturated fatty acids. Anaerobicity should be treated as a relative condition since complete anaerobiosis is hardly achievable in the laboratory. Ideally, researchers should provide all the details of their anaerobic set-up, to ensure reproducibility of results among different laboratories. A correction to this article is available online at http://eprints.whiterose.ac.uk/131930/ https://doi.org/10.1007/s00253-018-9036-

Measurement of inclusive jet charged-particle fragmentation functions in Pb plus Pb collisions at root S-NN=2.76 TeV with the ATLAS detector

© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/license/by/3.0/). Funded by SCOAP3