Infection of immature dendritic cells (DCs) by virus stimulates their maturation into APC. Infected DCs can also expose uninfected DCs to a panoply of cytokines/chemokines via paracrine signaling. ...Mathematical modeling suggests that a high rate of paracrine signaling is likely to occur among DCs located in three-dimensional space. Relatively little is known about how secreted factors modify the early response to virus infection. We used a transwell experimental system that allows passage of secreted factors, but not direct contact, between virus-infected DCs and uninfected DCs to investigate paracrine signaling responses. Paracrine signaling from infected DCs induced an antiviral-primed DC state distinct from that of mature virus-infected DCs that we refer to as antiviral-activated DCs (AVDCs). AVDCs had increased surface MHC class II and CD86 levels, but in contrast to virus-infected DCs, their MHC class I levels were unchanged. Imaging flow cytometry showed that AVDCs had an increased rate of phagocytosis compared with naive DCs. Experiments with IFN-beta cytokine indicated that it may be responsible for CD86, but not MHC class II regulation in AVDCs. Both IFN-inducible and IFN-independent genes are up-regulated in AVDCs. Notably, AVDCs are relatively resistant to virus infection in comparison to naive DCs and achieve accelerated and augmented levels of costimulatory molecule expression with virus infection. AVDCs show a distinct antiviral-primed state of DC maturation mediated by DC paracrine signaling. Although further in vivo study is needed, the characteristics of the AVDC suggest that it is well suited to play a role in the early innate-adaptive transition of the immune system.
Hydrochemical data of karst springs provide valuable insights into the internal hydrodynamical functioning of karst systems and support model structure identification. However, the collection of ...high‐frequency time series of major solute species is limited by analysis costs. In this study, we develop a method to retrieve the individual solute concentration time series and their uncertainty at high temporal resolution for karst springs by using continuous observations of electrical conductivity (EC$$ \mathrm{EC} $$) and low‐frequency ionic measurements. Due to the large ion content and non‐negligible concentrations of aqueous complexes in karst systems, the concentration of each solute species occurring as free ion and as part of aqueous complexes are computed separately. The concentration of species occurring as free ions are computed considering their contributions to the total EC$$ \mathrm{EC} $$, whereas the concentration of the species as part of complexes are obtained from speciation calculations. The pivotal role of the complexation processes for the reconstruction of solute concentration time series starting from the EC$$ \mathrm{EC} $$ signal is investigated in two karstic catchments with different geologies and temporal resolution of the available hydrochemical datasets, that is the Kerschbaum dolostone system in Austria and the Baget limestone system in France. The results show that complexation processes are significant and should be considered for the estimation of the total solute concentration in case of SO4, Ca, Mg and HCO3. The EC$$ \mathrm{EC} $$ signal of a karst spring can be used to interpolate and quantify the dynamics of those solutes characterized by large contribution (approximately >6%) to the total EC$$ \mathrm{EC} $$ and low relative variability, that is HCO3, Ca and Mg. Moreover, the presented method can be used to estimate concentrations of solutes when applied to karst systems with stationary and hydrogeochemical homogeneous contributing area. On the contrary, the method is affected by large uncertainty in case of dynamic systems characterized by varying contributions of water from different geological areas. This study aims to contribute to the problem of hydrogeochemical data availability and to support future works on karst systems conceptualization.
We present a methodology to retrieve major solute species in karst systems at high temporal resolution starting from continuous electrical conductivity and low‐resolution ionic measurements. The results show that complexation processes are significant for the estimation of the total concentration of SO4, Ca, Mg and HCO3. In case of karst systems with stationary and homogeneous hydrogeochemical contributing area, the EC$$ \mathrm{EC} $$ decomposition can be used in a predictive manner considering the probability distribution functions of the weight factors assigned to the major solute species.
Endoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic ...processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.
Donor peripheral blood mononuclear cells (PBMCs) and intraoperatively obtained periprosthetic fibroblast-like cells (PPFs) were (co-)cultured with ± macrophage-colony stimulating factor (MCSF) and Receptor Activator of NF-κB ligand (RANKL) in transwell and monolayer culture systems and examined for osteoclastogenic regulations MCSF, RANKL, osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) as well as the ability of bone resorption. Sequencing analysis compared dental and orthopaedic (co-)cultures.
Monolayer co-cultures of both origins expressed high levels of OPG, resulting in inhibition of osteolysis shown by resorption assay on dentin. The high OPG-expression, low RANKL/OPG ratios and a resulting inhibition of osteolysis were displayed by dental and orthopaedic PPFs in monolayer even in the presence of MCSF and RANKL, acting as osteoprotective and immunoregulatory cells. The osteoprotective function was only observed in monolayer cultures of dental and orthopaedic periprosthetic cells and downregulated in the transwell system. In transwell co-cultures of PBMCs/PPFs profound changes of gene expression, with a significant decrease of OPG (20-fold dental versus 100 fold orthopaedic), were identified. Within transwell cultures, which offer more
like conditions, RANKL/OPG ratios displayed similar high levels to the original periprosthetic tissue. For dental and orthopaedic implant loosening, overlapping findings in principal component and heatmap analysis were identified.
Thus, periprosthetic osteoclastogenesis may be a correlating immune process in orthopaedic and dental implant failure leading to comparable reactions with regard to osteoclast formation. The transwell cultures system may provide an
like model for the exploration of orthopaedic and dental implant loosening.
We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy ...range (COMPTEL, INTEGRAL; see Fig.
1
). These gamma-ray observations will be complemented by observations in the soft X-ray and (near-)infrared region with the corresponding telescopes placed on a separate satellite. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (“
GRIPS
”) mission with its three instruments Gamma-Ray Monitor (GRM), X-Ray Monitor (XRM) and InfraRed Telescope (IRT) addresses fundamental questions in ESA’s Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate
γ
-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.
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