What makes an allergen? Scheurer, S.; Toda, M.; Vieths, S.
Clinical and experimental allergy,
July 2015, Letnik:
45, Številka:
7
Journal Article
Recenzirano
Summary
Allergic diseases are an immune disorder reacting to certain type of allergen(s). Remarkably only a small number of proteins of the plant and animal proteome act as allergens. Therefore, ...allergens have been clustered according to their common structural, biochemical and functional features. Evidence has accumulated that some allergens possess intrinsic adjuvant properties to stimulate the innate immunity. The adjuvant properties appear to contribute to the allergenicity of the respective proteins, namely the ability to cause allergic sensitization in susceptible subjects or allergic reactions in sensitized individuals. Here, we discuss how allergens interact with the innate immune cells, in particular dendritic cells and epithelial cells, via binding to pattern recognition receptors, exhibiting proteolytic activities and/or inducting type 2 innate lymphoid cells (ILC2), thereby contributing to the sensitization and development of allergic diseases.
Imagine that a metallic wire is attached to a part of a large insulator, which itself exhibits no magnetization. It seems impossible for electrons in the wire to register where the wire is positioned ...on the insulator. Here we found that, using a Ni₈₁Fe₁₉/Pt bilayer wire on an insulating sapphire plate, electrons in the wire recognize their position on the sapphire. Under a temperature gradient in the sapphire, surprisingly, the voltage generated in the Pt layer is shown to reflect the wire position, although the wire is isolated both electrically and magnetically. This non-local voltage is due to the coupling of spins and phonons: the only possible carrier of information in this system. We demonstrate this coupling by directly injecting sound waves, which realizes the acoustic spin pumping. Our finding provides a persuasive answer to the long-range nature of the spin Seebeck effect, and it opens the door to 'acoustic spintronics' in which sound waves are exploited for constructing spin-based devices.
Pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase the risk for developing Parkinson’s disease in a dominantly inherited fashion. These pathogenic ...variants, of which G2019S is the most common, cause abnormally high kinase activity, and compounds that inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular processes, developing inhibitors that can selectively target the pathogenic variant while sparing normal LRRK2 activity could offer potential advantages in heterozygous carriers. We conducted a high-throughput screen and identified a single selective compound that preferentially inhibited G2019S-LRRK2. Optimization of this scaffold led to a series of novel, potent, and highly selective G2019S-LRRK2 inhibitors.
Gamification has been widely employed in the educational domain over the past eight years when the term became a trend. However, the literature states that gamification still lacks formal definitions ...to support the design and analysis of gamified strategies. This paper analysed the game elements employed in gamified learning environments through a previously proposed and evaluated taxonomy while detailing and expanding this taxonomy. In the current paper, we describe our taxonomy in-depth as well as expand it. Our new structured results demonstrate an extension of the proposed taxonomy which results from this process, is divided into five dimensions, related to the learner and the learning environment. Our main contribution is the detailed taxonomy that can be used to design and evaluate gamification design in learning environments.
Dynamic changes in synaptic strength are thought to be critical for higher brain function such as learning and memory. Alterations in synaptic strength can result from modulation of AMPA receptor ...(AMPAR) function and trafficking to synaptic sites. The phosphorylation state of AMPAR subunits is one mechanism by which cells regulate receptor function and trafficking. Receptor phosphorylation is in turn regulated by extracellular signals; these include neuronal activity, neuropeptides, and neuromodulators such as dopamine and norepinephrine (NE). Although numerous studies have reported that the neuropeptide pituitary adenylate cyclase activating polypeptide 38 (PACAP38) alters hippocampal CA1 synaptic strength and GluA1 synaptic localization, its effect on AMPAR phosphorylation state has not been explored. We determined that PACAP38 stimulation of hippocampal cultures increased phosphorylation of S845, and decreased phosphorylation of T840 on the GluA1 AMPAR subunit. Increases in GluA1 S845 phosphorylation primarily occurred via PAC1 and VPAC2 receptor activation, whereas a reduction in GluA1 T840 phosphorylation was largely driven by PAC1 receptor activation and to a lesser extent by VPAC1 and VPAC2 receptor activation. GluA1 S845 phosphorylation could be blocked by a PKA inhibitor, and GluA1 T840 dephosphorylation could be blocked by a protein phosphatase 1/2A (PP1/PP2A) inhibitor and was partly blocked by a NMDA receptor (NMDAR) antagonist. These results demonstrate that the neuropeptide PACAP38 inversely regulates the phosphorylation of two distinct sites on GluA1 and may play an important role modulating AMPAR function and synaptic plasticity in the brain.
Gamification refers to the attempt to transform different kinds of systems to be able to better invoke positive experiences such as the flow state. However, the ability of such intervention to invoke ...flow state is commonly believed to depend on several moderating factors including the user’s traits. Currently, there is a dearth of research on the effect of user traits on the results of gamification. Gamer types (personality traits related to gaming styles and preferences) are considered some of the most relevant factors affecting the individual’s susceptibility to gamification. Therefore, in this study we investigate how gamer types from the BrainHex taxonomy (achiever, conqueror, daredevil, mastermind, seeker, socializer and survivor) moderate the effects of personalized/non-personalized gamification on users’ flow experience (challenge-skill balance, merging of action and awareness, clear goals, feedback, concentration, control, loss of self-consciousness and
autotelic
experience), enjoyment, perception of gamification and motivation. We conducted a mixed factorial within-subject experiment involving 121 elementary school students comparing a personalized version against a non-personalized version of a gamified education system. There were no main effects between personalization and students’ flow experience, perception of gamification and motivation, and enjoyment. Our results also indicate patterns of characteristics that can lead students to the high flow experience (e.g., those who prefer to play multiplayer have a high flow experience in both personalized and non-personalized versions). Based on our results, we provided recommendations to advance the design of gamifed educational systems.
We propose an alternate fabrication technique of microchannel resonators based on an assembly method of three separate parts to form a microchannel resonator on a chip. The capability of the ...assembled microchannel resonator to detect mass is confirmed by injecting two liquids with different densities. The experimental and theoretical values of the resonator frequency shift are in agreement with each other, which confirms the consistency of the device. The noise level of the device is estimated from the Allan variance plot, so the minimum detectable mass of 230 fg after 16 s of operation is expected. By considering the time of the practical application of 1 ms, it is found that a detectable mass of around 8.51 pg is estimated, which is applicable for detecting flowing microparticles. The sub-pico to a few picogram levels of detection will be applicable for the mass analysis of flowing microparticles such as single cells and will be greatly beneficial for many fields such as chemistry, medicine, biology, and single-cell analysis.
•An innovative bimaterial cantilever beam was designed and fabricated as a temperature sensor to monitor the temperature of a single mammalian brown fat cell. The cantilever beam used in this ...research has an innovative structure fabricated from thin layers of silicon nitride and gold. In order for the cantilever beam to generate a large deflection in the presence of very small temperature variations, the bimaterial cantilever beam was conceived to be long and extremely thin, with the length in the range of micrometer and the thickness in the range of nanometer. There is no bimaterial cantilever reported in literature which is conceived for mammalian cell temperature measurements.•The paper is focused on the temperature calibration of bimaterial cantilever beam when it is operated in liquid. The set up for experimental characterization of bimaterial cantilever beam thermal behavior in liquid was presented.•The thermal modeling of temperature profile and deflection of bimaterial cantilever was studied. The heat transfer coefficient was experimentally calculated for different values of the applied temperature because it is an important factor for the temperature sensor calibration.
This paper presents the theoretical and experimental temperature profiles along a microcantilever beam operated in liquid and employed in this research as a temperature sensor. The main application of this cantilever beam is for sensing temperature variations of mammalian cells. The cantilever beam was microprocessed as a composite structure fabricated from thin layers of silicon nitride and gold. In order to achieve high sensitivity the cantilever beam was conceived with the length at microscale and the thickness at nanoscale dimensions. Very small temperature variations generated the deflection of the cantilever beam free end due to different values of the thermal expansion coefficients of silicon nitride and gold. The paper is focused on the temperature calibration of the cantilever beam temperature sensor when it is operated in liquid. In the paper a microwire heater was used as a localized heat source to generate the heat required for calibration purposes. The cantilever beam was immersed in the liquid and the heater temperature was varied from 27.5°C to 71.8°C. In analogy with the situation when temperature variations are sensed at certain distance from a cell in suspension the heater was located at 15μm distance from the cantilever beam. The experimental deflection values were compared with the theoretical deflection values and the heat transfer coefficient h of the system was calculated. At low temperatures the heat transfer coefficient value was 381W/m2K and at higher temperatures 642W/m2K. The experimental measurements illustrate that the cantilever beam deflection has the largest values when the heater was located near the midpoint of the cantilever beam. A systematic investigation of the cantilever beam deflection in liquid as a function of the applied heat is important for chemical and biological applications.
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