Syphilis and Raynaud's Disease

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USING RAINBOW TROUT CELL LINES AS A MODEL FOR UNDERSTANDING THE INNATE ANTI-FV3 IMMUNE RESPONSE

Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed the use of two rainbow trout cell lines, RTgutGC (intestinal origin) and RTG-2 (gonadal origin), previously shown to differ in susceptibility to FV3, thereby providing an excellent model to study innate anti-FV3 immune responses. Time-lapse infection videos and cell viability assays were used to quantify differences in the extent of cell death over time. RTG-2 exhibited greater cell death at a lower virus titre, compared with RTgutGC. The mechanism of cell death was investigated via DAPI staining and DNA laddering to observe nuclear condensation and intranucleosomal fragmentation, respectively, both hallmarks of apoptosis. Both cells underwent apoptosis in response to FV3. Moreover, UV-inactivated FV3 exhibited similar apoptotic cell death, suggesting that FV3-induced apoptosis is independent of productive virus replication. Likewise, poly I:C induction of IFN and ISGs inhibited virus replication, but had no effect on FV3-induced cell death. Using real-time RT-PCR IFN, ISG, and viral transcript expression was examined in both cell lines. Surprisingly FV3 elicited an equally poor IFN and ISG response in both cell lines, and was only detectable at 72h post-infection. Even when UV-inactivated, FV3 did not elicit a significant IFN response. However, viral transcript expression appears to be greater in the highly susceptible RTG-2 cell line. Further investigation into this difference in susceptibility between cell lines revealed that RTG-2 exhibited greater viral entry and cellular metabolism, which may account for the enhanced level of infection. Thus, FV3 appears to exhibit virulence factors that are independent of replication, yet the mechanisms governing susceptibility appear to be the result of intrinsic cellular features that are IFN-independent

The Role of Oxidative Stress in the Mechanisms of Ammonia-Induced Brain Swelling and Tolerance in the Goldfish (Carassius auratus)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in teleosts, in which blood ammonia concentrations can fluctuate markedly following feeding, exercise, and exposure to environmental ammonia. This study aimed to determine if exposure to high external ammonia (HEA; 5 mmol L-1) induced oxidative stress in the brain and liver of goldfish. HEA exposure led to 10-fold increases in internal ammonia and oxidative stress in the liver and brain. Oxidative damage was most pronounced in the brain, in which there were 114% increases in thiobarbituric-acid reactive substances (TBARS) and 3–fold increases in protein carbonyl content after 72 h HEA in warm-acclimated (14°C) goldfish. Notably, cold-water acclimation (4°C) completely attenuated the oxidative stress response in the goldfish brain and liver. This was accompanied by a marked diminution of the brain swelling response in cold-acclimated goldfish, whereas brain water volume increased by 20% in normothermic (14°C) individuals after 72 h HEA. The present study also demonstrated an increase in the activity of key antioxidant enzymes in the brain (CAT, GPx, GR) and liver (SOD, CAT, GR) during HEA, suggesting that goldfish are able to upregulate their antioxidant capacity in response to ammonia. In conclusion, oxidative stress appears to play a central role in the brain swelling process during acute hyperammonemia. Moreover, goldfish brains appear to have a high capacity to withstand oxidative stress in response to variations in internal ammonia. This likely explains why goldfish are more resilient to this homeostatic disturbance than mammalian brains

From theory to praxis

International audienceThis article is a description and discussion of a design research project in which we introduced a research idea about the influence of language on number concepts development into praxis on a school in grades K-3. Danish children have difficulties remembering the Danish number names because the Danish language resembles a primitive number concept in mathematical thinking. In the project, we renamed the numbers between 11-99 after the base-10 system. Our hypothesis was that this system would help Danish students to get a more secure concept about the base-10 system. The project lasted for three years ending in spring 2016. Our results were so convincing that the school decided to continue using the mathematical number names, and other schools that heard about the project seem to be interested in using the system as well. In other words, the project goes from being a top-down project to a bottom-up project

Coordination of a parallel proposition solver

In this paper we describe an experiment in which {sc Manifold is used to coordinate the interprocess communication in a parallelized proposition solver. {sc Manifold is very well suited for applications involving dynamic process creation and dynamically changing (ir)regular communication patterns among sets of independent concurrent cooperating processes. The idea in this case study is simple. The proposition solver consists of a fixed numbers of separate processing units which communicate with each other such that the output of one serves as the input for the other. Because one of the processing units performs a computation intensive job, we introduce a master/worker protocol to divide its computations. We show that this protocol implemented in {sc Manifold adds another hierarchic layer to the application but leaves the previous layers intact. This modularity of {sc Manifold offers the possibility to introduce concurrency step by step. We also verify the implementation of the proposition solver using a simple family of assertions and give some performance results

Computer assisted manipulation of algebraic process specifications

Specifications of system behaviour tend to become large. Analysis of such specifications requires automated tools. Most attention hitherto has been invested in fully automatic tools. We however believe that in many cases human intervention is required and we therefore propose a number of computer tools to transform process specifications. The concrete manipulation tools that we describe can eliminate constants, redundant sum variables and parameters, and allow to split variables ranging over complex datatypes. These tools can transform specifications with large finite state spaces to variants with state spaces being a fraction of their original size, and transform specifications with infinite state spaces to those with finite state spaces

Distributionally robust chance constrained Markov decision process with Kullback-Leibler divergence

This paper considers the distributionally robust chance constrained Markov decision process with random reward and ambiguous reward distribution. We consider individual and joint chance constraint cases with Kullback-Leibler divergence based ambiguity sets centered at elliptical distributions or elliptical mixture distributions, respectively. We derive tractable reformulations of the distributionally robust individual chance constrained Markov decision process problems and design a new hybrid algorithm based on the sequential convex approximation and line search method for the joint case. We carry out numerical tests with a machine replacement problem

Hvordan og hvorfor opstår der benspænd for at udvikle regnestrategier?

Kommentar til Pernille Bødtker Sunde: “Adaptivitet og fleksibilitet: Regnestrategier i de yngste klasser”, MONA, 2022(2)