Selective activation of JNK/SAPK by interleukin-1 in rabbit liver is mediated by MKK7

AbstractActivation of jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) by interleukin-1 (IL-1) has been reported in many cells and in rabbit liver. Here we report selective activation of JNK/SAPK, without activation of p38 or p42 mitogen-activated protein kinases (MAPKs), by IL-1 in rabbit liver. We identified an IL-1 regulated JNK/SAPK activator present in rabbit liver using S Sepharose chromatography. It was purified and immunoprecipitated by two antisera to MAP kinase kinase 7 (MKK7). It was not recognised by an antibody to MKK4. We conclude that MKK7 is the activator of JNK/SAPK activated by IL-1 in liver and that JNK/SAPK is the only MAPK activated by IL-1 in liver

Inhibitor of Apoptosis Proteins as Novel Targets in Inflammatory Processes

Objective: Inhibitor of apoptosis proteins (IAPs), such as X-linked or cellular IAP 1/2 (XIAP, cIAP1/2), are important regulators of apoptosis. IAP antagonists are currently under clinical investigation as anticancer agents. Interestingly, IAPs participate in the inflammation-associated TNF receptor signaling complex and regulate NFκB signaling. This raises the question about the role of IAPs in inflammation. Here, we investigated the anti-inflammatory potential of IAP inhibitors and the role of IAPs in inflammatory processes of endothelial cells. Methods and Results: In mice, the small molecule IAP antagonist A-4.10099.1 (ABT) suppressed antigen-induced arthritis, leukocyte infiltration in concanavalin A-evoked liver injury, and leukocyte transmigration in the TNFα-activated cremaster muscle. In vitro, we observed an attenuation of leukocyte– endothelial cell interaction by downregulation of the intercellular adhesion molecule-1. ABT did not impair NFκB signaling but decreased the TNFα-induced activation of the TGF-β–activated kinase 1, p38, and c-Jun N-terminal kinase. These effects are based on the proteasomal degradation of cIAP1/2 accompanied by an altered ratio of the levels of membrane-localized TNF receptor-associated factors 2 and 5. Conclusion: Our results reveal IAP antagonism as a profound anti-inflammatory principle in vivo and highlight IAPs as important regulators of inflammatory processes in endothelial cells

Multiple Conclusion Rules in Logics with the Disjunction Property

We prove that for the intermediate logics with the disjunction property any basis of admissible rules can be reduced to a basis of admissible m-rules (multiple-conclusion rules), and every basis of admissible m-rules can be reduced to a basis of admissible rules. These results can be generalized to a broad class of logics including positive logic and its extensions, Johansson logic, normal extensions of S4, n-transitive logics and intuitionistic modal logics

Strategies for achieving viral hepatitis C micro-elimination in the Netherlands.

The Netherlands is striving to achieve national elimination of the hepatitis C virus (HCV) as one of the first countries worldwide. The favorable HCV epidemiology with both low prevalence and incidence, together with access to care and treatment, present excellent conditions to further build on towards this objective. The Dutch national plan on viral hepatitis, introduced in 2016, defines targets in the HCV healthcare cascade and provides a structural framework for the development of elimination activities. Since many different stakeholders are involved in HCV care in the Netherlands, focus has been placed on micro-elimination initiatives as a pragmatic and efficient approach. These numerous micro-eliminations projects have brought the Netherlands closer to HCV elimination. In the near future, efforts specifically have to be made in order to optimize case-finding strategies and to successfully accomplish the nationwide implementation of the registration and monitoring system of viral hepatitis mono-infections, before this final goal can be reached. The upcoming years will then elucidate if the Dutch' hands on approach has resulted in sufficient progress against HCV and if the Netherlands will lead the way towards nationwide HCV elimination

A Fibred Tableau Calculus for Modal Logics of Agents

In previous works we showed how to combine propositional multimodal logics using Gabbay's \emph{fibring} methodology. In this paper we extend the above mentioned works by providing a tableau-based proof technique for the combined/fibred logics. To achieve this end we first make a comparison between two types of tableau proof systems, (\emph{graph} $\&$ \emph{path}), with the help of a scenario (The Friend's Puzzle). Having done that we show how to uniformly construct a tableau calculus for the combined logic using Governatori's labelled tableau system \KEM. We conclude with a discussion on \KEM's features

Self-assembly of ordered wurtzite/rock salt heterostructures—A new view on phase separation in MgxZn1−xO

The self-assembled formation of ordered, vertically stacked rocksalt/wurtzite Mg x Zn 1−xO heterostructures by planar phase separation is shown. These heterostructures form quasi “natural” two-dimensional hetero-interfaces between the different phases upon annealing of MgO-oversaturated wurtzite Mg x Zn 1−xO layers grown by plasma-assisted molecular beam epitaxy on c-plane sapphire substrates. The optical absorption spectra show a red shift simultaneous with the appearance of a cubic phase upon annealing at temperatures between 900 °C and 1000 °C. Transmission electron microscopy reveals that these effects are caused by phase separation leading to the formation of a vertically ordered rock salt/wurtzite heterostructures. To explain these observations, we suggest a phase separation epitaxy model that considers this process being initiated by the formation of a cubic (Mg,Zn)Al2O4 spinel layer at the interface to the sapphire substrate, acting as a planar seed for the epitaxial precipitation of rock salt Mg x Zn 1−xO. The equilibrium fraction x of magnesium in the resulting wurtzite (rock salt) layers is approximately 0.15 (0.85), independent of the MgO content of the as-grown layer and determined by the annealing temperature. This model is confirmed by photoluminescence analysis of the resulting layer systems after different annealing temperatures. In addition, we show that the thermal annealing process results in a significant reduction in the density of edge- and screw-type dislocations, providing the possibility to fabricate high quality templates for quasi-homoepitaxial growth

Human fetal microglia acquire homeostatic immune-sensing properties early indevelopment

Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were heterogeneous at all studied GWs. Microglia start to mature during this developmental period and increasingly resemble adult microglia with CNS-surveilling properties. Chromatin accessibility increases during development with associated transcriptional networks reflective of adult microglia. Thus, during early fetal development, microglia progress toward a more mature, immune-sensing competent phenotype, and this might render the developing human CNS vulnerable to environmental perturbations during early pregnancy

Older Adult Compendium of Physical Activities: Energy Costs of Human Activities in Adults Aged 60 and Older

Purpose: To describe the development of a Compendium for estimating the energy costs of activities in adults ≥60 years (OA Compendium). Methods: Physical activities (PAs) and their metabolic equivalent of task (MET) values were obtained from a systematic search of studies published in 4 sport and exercise databases (PubMed, Embase, SPORTDiscus (EBSCOhost), and Scopus) and a review of articles included in the 2011 Adult Compendium that measured PA in older adults. MET values were computed as the oxygen cost (VO2, mL/kg/min) during PA divided by 2.7 mL/kg/min (MET60+) to account for the lower resting metabolic rate in older adults. Results: We identified 68 articles and extracted energy expenditure data on 427 PAs. From these, we derived 99 unique Specific Activity codes with corresponding MET60+ values for older adults. We developed a website to present the OA Compendium MET60+ values: https://pacompendium.com. Conclusion: The OA Compendium uses data collected from adults ≥60 years for more accurate estimation of the energy cost of PAs in older adults. It is an accessible resource that will allow researchers, educators, and practitioners to find MET60+ values for older adults for use in PA research and practice

Comet 322P/<i>SOHO</i>1: an asteroid with the smallest perihelion distance?

We observed comet 322P/SOHO 1 (P/1999 R1) from the ground and with the Spitzer Space Telescope when it was between 2.2 and 1.2 au from the Sun. These are the first observations of any Solar and Heliospheric Observatory (SOHO)-discovered periodic comet by a non-solar observatory and allow us to investigate its behavior under typical cometary circumstances. 322P appeared inactive in all images. Its light curve suggests a rotation period of 2.8 ± 0.3 hr and has an amplitude ≳0.3 mag, implying a density of at least 1000 kg m−3, considerably higher than that of any known comet. It has average colors of g' - r'=0.52 ± 0.04 and r' - i' = 0.03 ± 0.06. We converted these to Johnson colors and found that the V − R color is consistent with average cometary colors, but R − I is somewhat bluer; these colors are most similar to V- and Q-type asteroids. Modeling of the optical and IR photometry suggests it has a diameter of 150–320 m and a geometric albedo of 0.09–0.42, with diameter and albedo inversely related. Our upper limits to any undetected coma are still consistent with a sublimation lifetime shorter than the typical dynamical lifetimes for Jupiter-family comets. These results suggest that 322P may be of asteroidal origin and only active in the SOHO fields of view via processes different from the volatile-driven activity of traditional comets. If so, it has the smallest perihelion distance of any known asteroid