Effects of ventilation strategy on distribution of lung inflammatory cell activity

Introduction: Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin administration. Methods: Anesthetized sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either injurious or protective mechanical ventilation (n = 6 per group). We used positron emission tomography to obtain images of regional perfusion and shunting with infused 13N[nitrogen]-saline and images of neutrophilic inflammation with 18F-fluorodeoxyglucose (18F-FDG). The Sokoloff model was used to quantify 18F-FDG uptake (Ki), as well as its components: the phosphorylation rate (k3, a surrogate of hexokinase activity) and the distribution volume of 18F-FDG (Fe) as a fraction of lung volume (Ki = Fe × k3). Regional gas fractions (fgas) were assessed by examining transmission scans. Results: Before endotoxin administration, protective (vs. injurious) ventilation was associated with a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2) (351 ± 117 vs. 255 ± 74 mmHg; P < 0.01) and higher whole-lung fgas (0.71 ± 0.12 vs. 0.48 ± 0.08; P = 0.004), as well as, in dependent regions, lower shunt fractions. Following 2 h of endotoxemia, PaO2/FiO2 ratios decreased in both groups, but more so with injurious ventilation, which also increased the shunt fraction in dependent lung. Protective ventilation resulted in less nonaerated lung (20-fold; P < 0.01) and more normally aerated lung (14-fold; P < 0.01). Ki was lower during protective (vs. injurious) ventilation, especially in dependent lung regions (0.0075 ± 0.0043/min vs. 0.0157 ± 0.0072/min; P < 0.01). 18F-FDG phosphorylation rate (k3) was twofold higher with injurious ventilation and accounted for most of the between-group difference in Ki. Dependent regions of the protective ventilation group exhibited lower k3 values per neutrophil than those in the injurious ventilation group (P = 0.01). In contrast, Fe was not affected by ventilation strategy (P = 0.52). Lung neutrophil counts were not different between groups, even when regional inflation was accounted for. Conclusions: During systemic endotoxemia, protective ventilation may reduce the magnitude and heterogeneity of pulmonary inflammatory cell metabolic activity in early lung injury and may improve gas exchange through its effects predominantly in dependent lung regions. Such effects are likely related to a reduction in the metabolic activity, but not in the number, of lung-infiltrating neutrophils

A Cautionary Tale: MARVELS Brown Dwarf Candidate Reveals Itself To Be A Very Long Period, Highly Eccentric Spectroscopic Stellar Binary

We report the discovery of a highly eccentric, double-lined spectroscopic binary star system (TYC 3010-1494-1), comprising two solar-type stars that we had initially identified as a single star with a brown dwarf companion. At the moderate resolving power of the MARVELS spectrograph and the spectrographs used for subsequent radial-velocity (RV) measurements (R ~ <30,000), this particular stellar binary mimics a single-lined binary with an RV signal that would be induced by a brown dwarf companion (Msin(i)~50 M_Jup) to a solar-type primary. At least three properties of this system allow it to masquerade as a single star with a very low-mass companion: its large eccentricity (e~0.8), its relatively long period (P~238 days), and the approximately perpendicular orientation of the semi-major axis with respect to the line of sight (omega~189 degrees). As a result of these properties, for ~95% of the orbit the two sets of stellar spectral lines are completely blended, and the RV measurements based on centroiding on the apparently single-lined spectrum is very well fit by an orbit solution indicative of a brown dwarf companion on a more circular orbit (e~0.3). Only during the ~5% of the orbit near periastron passage does the true, double-lined nature and large RV amplitude of ~15 km/s reveal itself. The discovery of this binary system is an important lesson for RV surveys searching for substellar companions; at a given resolution and observing cadence, a survey will be susceptible to these kinds of astrophysical false positives for a range of orbital parameters. Finally, for surveys like MARVELS that lack the resolution for a useful line bisector analysis, it is imperative to monitor the peak of the cross-correlation function for suspicious changes in width or shape, so that such false positives can be flagged during the candidate vetting process.Comment: 16 pages, 11 figures, 6 table

On the Monophyly and Relationships of Several Genera of Hylini (Anura: Hylidae: Hylinae), with Comments on Recent Taxonomic Changes in Hylids

We present a molecular phylogenetic analysis of the hylid tribe Hylini, with the goals of testing the monophyly of the genera Duellmanohyla, Isthmohyla, and Ptychohyla and providing a discussion on the monophyly of Bromeliohyla, Charadrahyla, Ecnomiohyla, Exerodonta, Megastomatohyla, and Sarcohyla. Our results indicate the paraphyly of Ptychohyla, with Bromeliohyla and Duellmanohyla nested within it, and, as in previous analyses, the paraphyly of Duellmanohyla (due to Ptychohyla legleri and P. salvadorensis being nested within it). To resolve this situation, we restrict the contents of Ptychohyla, redelimit those of Duellmanohyla and Bromeliohyla, and erect two new genera, one to include the former Ptychohyla panchoi and P. spinipollex, and the other for the former Ptychohyla acrochorda, P. sanctaecrucis, P. zoque, and tentatively, P. erythromma. Exerodonta as currently defined is not monophyletic, inasmuch as Exerodonta juanitae is nested within Charadrahyla. Consequently, we transfer this species and, tentatively, E. pinorum to Charadrahyla. Also, we discuss some possible taxonomic problems within Exerodonta. Our results indicate that Isthmohyla is polyphyletic, the bromeliad-dwelling Isthmohyla melacaena being the sister taxon of our only exemplar of Bromeliohyla, B. bromeliacia. For this reason, we transfer I. melacaena to Bromeliohyla, rendering Isthmohyla monophyletic. The former Isthmohyla pictipes Group is shown to be paraphyletic due to having the non-monophyletic I. pseudopuma Group within it. Accordingly, we recognize a redelimited I. pseudopuma Group (contents: I. infucata and I. pseudopuma), an I. zeteki Group (contents: I. picadoi and I. zeteki), and a newly defined I. tica Group (contents: I. angustilineata, I. calypsa, I. debilis, I. graceae, I. lancasteri, I. pictipes, I. tica, I. rivularis, and, tentatively, I. insolita and I. xanthosticta). The three groups of Isthmohyla are supported by molecular evidence with jackknife support values > 90%, and two of them by putative morphological synapomorphies. We discuss the recognition of Dryophytes, Hyliola, Rheohyla, and Sarcohyla and whether it is useful to recognize Anotheca, Diaglena, and Triprion as three distinct, monotypic genera. Finally, we discuss a recent taxonomic proposal involving changes in rank and from ranked to unranked names in hylids that overall we consider to have been poorly justified and only superficially discussed.Fil: Faivovich, Julián. Universidad de Buenos Aires; ArgentinaFil: Pereyra, Martín Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Luna, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Hertz, Andreas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Blotto Acuña, Boris Leonardo. University Of Massachusetts Boston;Fil: Vásquez-Almazán, Carlos R.. Senckenberg Forschungsinstitut Und Naturmuseum;Fil: McCranie, James R.. Universidade de Sao Paulo; BrasilFil: Sánchez, David A.. Universidad de San Carlos de Guatemala; GuatemalaFil: Baêta, Délio. Universidad de San Carlos de Guatemala; GuatemalaFil: Araujo-Vieira, Katyuscia. University Of Texas At Arlington;Fil: Köhler, Gunther. Unesp-universidade Estadual Paulista;Fil: Kubicki, Brian. Universidade Federal do Rio de Janeiro; BrasilFil: Campbell, Jonathan A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Frost, Darrel R.. Senckenberg Forschungsinstitut Und Naturmuseum;Fil: Wheeler, Ward C.. Costa Rican Amphibian Research Center; Costa RicaFil: Haddad, Célio F.B.. University Of Texas At Arlington

Very Low Mass Stellar and Substellar Companions to Solar-Like Stars From MARVELS V: A Low Eccentricity Brown Dwarf from the Driest Part of the Desert, MARVELS-6b

We describe the discovery of a likely brown dwarf (BD) companion with a minimum mass of 31.7 +/- 2.0 M_Jup to GSC 03546-01452 from the MARVELS radial velocity survey, which we designate as MARVELS-6b. For reasonable priors, our analysis gives a probability of 72% that MARVELS-6b has a mass below the hydrogen-burning limit of 0.072 M_Sun, and thus it is a high-confidence BD companion. It has a moderately long orbital period of 47.8929 +0.0063/-0.0062 days with a low eccentricty of 0.1442 +0.0078/-0.0073, and a semi-amplitude of 1644 +12/-13 m/s. Moderate resolution spectroscopy of the host star has determined the following parameters: T_eff = 5598 +/- 63, log g = 4.44 +/- 0.17, and [Fe/H] = +0.40 +/- 0.09. Based upon these measurements, GSC 03546-01452 has a probable mass and radius of M_star = 1.11 +/- 0.11 M_Sun and R_star = 1.06 +/- 0.23 R_Sun with an age consistent with less than ~6 Gyr at a distance of 219 +/- 21 pc from the Sun. Although MARVELS-6b is not observed to transit, we cannot definitively rule out a transiting configuration based on our observations. There is a visual companion detected with Lucky Imaging at 7.7 arcsec from the host star, but our analysis shows that it is not bound to this system. The minimum mass of MARVELS-6b exists at the minimum of the mass functions for both stars and planets, making this a rare object even compared to other BDs.Comment: 15 pages, 15 figures, 5 tables. Accepted for publication in The Astronomical Journa

Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under serum-/xeno-free conditions in a microcarrier-based bioreactor culture system

Copyright © 2020 de Almeida Fuzeta, Bernardes, Oliveira, Costa, Fernandes-Platzgummer, Farinha, Rodrigues, Jung, Tseng, Milligan, Lee, Castanho, Gaspar, Cabral and da Silva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases. EVs are derived from cell membranes, allowing high biocompatibility to target cells, while their small size makes them ideal candidates to cross biological barriers. Despite the promising potential of EVs for therapeutic applications, robust manufacturing processes that would increase the consistency and scalability of EV production are still lacking. In this work, EVs were produced by MSC isolated from different human tissue sources [bone marrow (BM), adipose tissue (AT), and umbilical cord matrix (UCM)]. A serum-/xeno-free microcarrier-based culture system was implemented in a Vertical-WheelTM bioreactor (VWBR), employing a human platelet lysate culture supplement (UltraGROTM-PURE), toward the scalable production of MSC-derived EVs (MSC-EVs). The morphology and structure of the manufactured EVs were assessed by atomic force microscopy, while EV protein markers were successfully identified in EVs by Western blot, and EV surface charge was maintained relatively constant (between −15.5 ± 1.6 mV and −19.4 ± 1.4 mV), as determined by zeta potential measurements. When compared to traditional culture systems under static conditions (T-flasks), the VWBR system allowed the production of EVs at higher concentration (i.e., EV concentration in the conditioned medium) (5.7-fold increase overall) and productivity (i.e., amount of EVs generated per cell) (3-fold increase overall). BM, AT and UCM MSC cultured in the VWBR system yielded an average of 2.8 ± 0.1 × 1011, 3.1 ± 1.3 × 1011, and 4.1 ± 1.7 × 1011 EV particles (n = 3), respectively, in a 60 mL final volume. This bioreactor system also allowed to obtain a more robust MSC-EV production, regarding their purity, compared to static culture. Overall, we demonstrate that this scalable culture system can robustly manufacture EVs from MSC derived from different tissue sources, toward the development of novel therapeutic products.unding received by iBB-Institute for Bioengineering and Biosciences from the Portuguese Foundation for Science and Technology (FCT) (UID/BIO/04565/2020) and through the projects PTDC/EQU-EQU/31651/2017, PTDC/BBB-BQB/1693/2014, and PTDC/BTM-SAL/31057/2017 is acknowledged. Funding received from POR de Lisboa 2020 through the project PRECISE – Accelerating progress toward the new era of precision medicine (Project N. 16394) is also acknowledged. MAF (PD/BD/128328/2017) and FO (PD/BD/135046/2017) acknowledge FCT for the Ph.D. fellowships and DG (SFRH/BPD/109010/2015) for the Post-Doctoral fellowship.info:eu-repo/semantics/publishedVersio

Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit

TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged (~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of 0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of ~2 years. The best Keplerian orbital fit parameters were found to have a period of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for short period stellar companions to solar-like (Teff ~< 6000 K) stars. One possible way to create such a system would be if a triple-component stellar multiple broke up into a short period, low q binary during the cluster dispersal phase of its lifetime. A candidate tertiary body has been identified in the system via single-epoch, high contrast imagery. If this object is confirmed to be co-moving, we estimate it would be a dM4 star. We present these results in the context of our larger-scale effort to constrain the statistics of low mass stellar and brown dwarf companions to FGK-type stars via the MARVELS survey.Comment: 22 pages; accepted in A

COVID-19 Vaccination of Individuals with Down Syndrome—Data from the Trisomy 21 Research Society Survey on Safety, Efficacy, and Factors Associated with the Decision to Be Vaccinated

Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068