Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast ...cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro.
We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes.
We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface.
These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.
Epilogue M. Soluri
The Pluto System After New Horizons,
08/2021
Book Chapter
To be sure, this was a historic engineering and scientific feat unlikely to be repeated within our lifetimes. So similar to the listener in the lecture room in Whitman’s poem, “… the Learn’d ...Astronomer,” I was not just attending, but essentially in residence at the Johns Hopkins University’s Applied Physics Lab (APL), documenting the brain trust behind NASA’s New Horizon’s mission to the Pluto system.
Although the photograph below was taken May 28, 2015, it is likely that during the 1960s “race to space” the seeds for the exploration of the solar system began taking root in the imaginations of
The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To ...understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.
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•The GAF unstructured polyQ domain is not required for localizing to nuclear foci•The GAF DBD is necessary and sufficient for localization to condensed nuclear foci•GAF subnuclear foci correspond to heterochromatic AAGAG satellite repeats•GAF is required for heterochromatin formation and silencing of satellite repeats
Gaskill et al. demonstrate that in addition to the previously identified role of the pioneer factor GAF in activating the initial zygotic transcription in Drosophila, GAF is required to establish silencing of highly abundant AAGAG satellite repeats. This silencing occurs in subnuclear GAF foci established through DNA binding.
The metropolitan area of Rio de Janeiro is one of the twenty biggest urban agglomerations in the world, with 11 million inhabitants in the metropolitan area, and has a high population density, with ...1700
hab.
km
−2. For this aerosol source apportionment study, the atmospheric aerosol sampling was performed at ten sites distributed in different locations of the metropolitan area from September/2003 to December/2005, with sampling during 24
h on a weekly basis. Stacked filter units (SFU) were used to collect fine and coarse aerosol particles with a flow rate of 17
L
min
−1. In both size fractions trace elements were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) as well as water-soluble species by Ion-Chromatography (IC). Also gravimetric analysis and reflectance measurements provided aerosol mass and black carbon concentrations. Very good detection limits for up to 42 species were obtained. Mean annual PM
10 mass concentration ranged from 20 to 37
μg
m
−3, values that are within the Brazilian air quality standards. Receptor models such as principal factor analysis, cluster analysis and absolute principal factor analysis were applied in order to identify and quantify the aerosol sources. For fine and coarse modes, circa of 100% of the measured mass was quantitatively apportioned to relatively few identified aerosol sources. A very similar and consistent source apportionment was obtained for both fine and coarse modes for all 10 sampling sites. Soil dust is an important component, accounting for 22–72% and for 25–48% of the coarse and fine mass respectively. On the other hand, anthropogenic sources as vehicle traffic and oil combustion represent a relatively high contribution (52–75%) of the fine aerosol mass. The joint use of ICP-MS and IC analysis of species in aerosols has proven to be reliable and feasible for the analysis of large amount of samples, and the coupling with receptor models provided an excellent method for quantitative aerosol source apportionment in large urban areas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ICOS and CD28 are expressed by T cells and are involved in costimulation of cytokine production in T helper (TH) cells. ICOS binds B7h expressed by several cell types, whereas CD28 binds B7.1 and ...B7.2 expressed by activated antigen presenting cells. This work investigated the role of B7h and B7.1 in TH17 and TH9 cell differentiation by assessing activity of recombinant B7h-Fc and B7.1-Fc on human naïve TH cells activated in the presence of different combinations of exogenous cytokines. In the presence of TGF-β1 and IL-1β (TH17 promoting condition), B7h-Fc was more effective than B7.1-Fc in inducing IL-17A and IL-10 secretion, whereas B7.1-Fc was more effective in inducing IL-17F. Dual costimulation with B7h-Fc and B7.1-Fc displayed an intermediate pattern with predominance of IL-17F over IL-17A, secretion of high levels of IL-10, and secretion of IL-9 levels lower than those induced by B7.1-Fc alone. In the presence of TGF-β1 and IL-4 (TH9 promoting condition), B7h-Fc induced IL-17A only, whereas B7.1-Fc induced also IL-17F, IL-10, and high levels of IL-9. Experiments on memory TH cells showed that B7h-Fc mainly supported secretion of IL-17A and IL-10, whereas B7.1-Fc supported secretion of IL-17A, IL-17F, IL-10, and IL-9. These data indicate that B7h and B7.1 play different roles in modulation of TH17 and TH9 differentiation. This plasticity might be important in the immune response to pathogens and tumors, and in the development of autoimmune diseases, and should be taken in consideration in designing of immunotherapeutic protocols triggering ICOS or CD28.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological ...damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (
= 6/group) tidal volume (V
) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH
O, fraction of inspired oxygen (FiO
) = 0.4; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V
values (
= 1200; mean V
= 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH
0/ml and 2.0 ± 0.8 cmH
0/ml,
= 0.005; median interquartile range, VCV 20.4% 7.9-33.1 and VV 5.4% 3.1-8.8,
= 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.
Super Spatial Resolution (SSR) method for scintigraphic imaging Trinci, G.; Massari, R.; Scandellari, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2011, Volume:
626
Journal Article
Peer reviewed
This work describes an innovative patented Super Spatial Resolution (SSR) method applied to scintigraphic devices. The aim of Super Resolution (SR) techniques is to enhance the resolution of an ...imaging system, using information from several images. SR reconstruction may be considered as a second generation problem of Image Restoration. It combines several slightly different Low Resolution (LR) images to obtain a High Resolution (HR) image. SR techniques are, widely, described in scientific literature mainly for applications in video communication, object recognition and image compression.
In this paper we focus to apply the SR task to the scintigraphic imaging. Specifically, it is described as a patented method that uses a High Resolution Scintigraphic Camera (HRSC) to collect and process a set of scintigraphic images, in view of obtaining a very high resolution image.
The HRSC device, which is currently used in Medical Imaging, is based on a parallel square holes collimator and on a Hamamatsu H8500 Position Sensitive Photomultiplier Tubes (PSPMT).
The SSR method is applied to the synthetic images of three different phantoms, to verify the effective spatial resolution values. The results confirm that it is possible to achieve optimal spatial resolution values at different depths, useful in small object and small animal imaging.
Our study confirms the feasibility of a very high resolution system in scintigraphic imaging and the possibility to have gamma cameras using the SSR method, to perform clinical applications on patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lung transplantation is the treatment of choice for end-stage pulmonary diseases. In order to avoid or reduce pulmonary and systemic complications, mechanical ventilator settings have an important ...role in each stage of lung transplantation. In this respect, the use of mechanical ventilation with a tidal volume of 6 to 8 ml kg predicted body weight, positive end-expiratory pressure of 6 to 8 cmH2O and a plateau pressure lower than 30 cmH2O has been suggested for the donor during surgery, and for the recipient both during and after surgery. For the present review, we systematically searched the PubMed database for articles published from 2000 to 2014 using the following keywordslung transplantation, protective mechanical ventilation, lung donor, extracorporeal membrane oxygenation, recruitment manoeuvres, extracorporeal CO2 removal and noninvasive ventilation.
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